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[ [ "splenic pseudoaneurysms ( spa ) are a serious sequela of blunt traumatic injury to the spleen .", "they are very rare with fewer than 200 cases reported in english literature in 2006 and their incidence is virtually unknown .", ", we share our experience at an urban level 1 trauma center of managing a hemodynamically stable pediatric patient who sustained a grade iii / iv splenic laceration following blunt trauma with follow - up imaging demonstrative of splenic pseudoaneurysm and proposed algorithm to manage such a case .", "although the american pediatric surgical association does not recommend routine follow - up imaging in pediatric trauma patients regardless of grade of injury , several reviews have described the potential benefits of follow - up ct imaging for detection of pseudoaneurysm . here", "spa have a high risk of rupture and have been reported to be fatal if left untreated in adults . in the setting of trauma , spa can form 1 to 8 days after the blunt splenic injury and could be missed on the initial imaging .", "however , the management in pediatric patients is poorly defined . with regards to spa ," ], [ "a 15 year - old male with no significant past medical history presented to the emergency room complaining of severe abdominal pain of acute onset after sustaining injury to his left side while playing football .", "interventional radiology was consulted and on hospital - day 5 ; they performed a splenic arteriogram which demonstrated multiple pseudoaneurysms arising from the second order splenic artery branches .", "he was observed for another 24 h post - procedure without event and was discharged the next day after receiving the pneumococcal and meningococcal vaccines .", "primary survey included a focused assessment with sonography for trauma ( fast ) , which was positive for free fluid in the abdomen ." ], [ "splenic artery pseudoaneurysms ( spa ) remain a rare but potentially fatal pathology following blunt trauma which is managed non - operatively .", "mayglothling presented their algorithm with aggressive angiography and embolization as a useful adjunct to non - operative management of adolescents with blunt splenic injuries .", "management of spa can be operative entailing splenectomy with or without pancreatectomy or non - operative , using endovascular techniques .", ". pediatric splenic trauma may be more suitable for non - operative management than that of adult because the differences in pathophysiology of the injury ." ], [ "questions still remain regarding the timing of repeat imaging for diagnosis of spa following non - operative blunt splenic trauma , which patients should be imaged , and how to manage spa upon diagnosis .", "we believe that our proposed management algorithm timely detect formation of delayed spa formation and addresses the possible fatal disease course of pediatric spa .", "the limited existing literature leaves us with a still unclear algorithm for the management of non - operative blunt splenic trauma in pediatric patients .", "more clinical study and basic science research is warranted to study the disease process of spa in pediatric patient ." ], [], [], [], [], [ "roger chen zhu review of literature , preparation of case report , and writing of the paper ." ], [], [] ]

[ [ "do the existing regulatory standards of practice for nurses adequately address safety critical issues in relation to transitions in care ? in this paper , we report the findings of a study undertaken with one of canada 's provincial regulatory colleges to develop a greater understanding of the kinds of regulatory requirements needed to support safe care transitions .", "transitions in care are arguably one of the most important and challenging safety issues in healthcare today .", ", we examine regulatory requirements for safe client handovers , illuminating the tension between traditional and complexity informed approaches to professional standards of practice .", "transitions are a complex business that require a high degree of context - specific coordination and communication among different people with different backgrounds and skills ." ], [ "overall , there is a dearth of empirical evidence that considers the link between regulatory standards of practice and safe transitions in care .", "yet , to have a positive impact on the quality of care , regulatory standards of practice have to be contextually relevant , evidence based , and keep pace with the rapidly changing health care environment .", "handoffs , transfer of accountability , and handover are terms used to describe the transfer of information and the accountability for care .", "specific to nursing , terms such as shift change , change - over , and report are used to mark the end of a time period and to transfer the accountability for care to the next .", "communication at the time of handover should result in a clear understanding about who is responsible for which aspects of the client 's care . " ], [ "complexity theory reminds us that healthcare providers enable and constrain each other in local interactions , and these patterns of interaction constitute control and order . and", "because complex systems interact with other complex systems , tension and paradox are a common theme seemingly opposing forces of competition and cooperation can work together in ways that can never be fully predicted or resolved .", " the integration of complexity and traditional approaches to understanding processes of care during transition points will help nurses develop more comprehensive understanding of their work environment and client and family needs .", "whereas traditional scientific thinking assumes all issues can be resolved , complexity theory is comfortable with and values inherent tension between different parts of the system .", "a complexity lens helps nurses and other health professionals to develop a fuller understanding of the ways in which people and processes of care are interconnected , emergent and how relationship - rich networks and shared sense - making enable them to manage uncertainty more effectively .", "newcomers to complexity science may imagine a picture of utter confusion when they hear someone refer to healthcare as chaotic or complex . for students of complexity science , however , chaos is not about utter confusion , but rather about the existence of patterns where we thought there were none . unlike traditional models of science , which are cast in the form of linear and proportional relationships between cause and effect ,", "in contrast , from a complexity perspective , healthcare providers respond to their own particular local context , producing diversity of agent behaviours and client and family experiences ." ], [ "sixty - six interviews were conducted with a wide range of health care providers ( e.g. , nurses , physicians , pharmacists , social workers , physio- and occupational therapy , and pastoral care ) from a variety of practice settings ( e.g. , acute care , long - term care , palliative care , mental health , and corrections ) .", "the initial codes were then organized into provisional categories to build a coding framework divided into major themes and subthemes . the author and a research assistant conducted all aspects of the coding , first independently and then we compared and discussed categories until consensus was reached .", "subsequently , we engaged the project team in a one - day workshop to review and validate preliminary findings and explore implications for each profession 's regulatory framework .", "four generic ai processes were incorporated into design and execution of this study , including ( 1 ) using the positive as the focus of inquiry ; ( 2 ) inquiring into exceptionally positive moments ; ( 3 ) sharing the stories and identifying life - giving forces ; and ( 4 ) creating shared images of a preferred future .", "the appreciative inquiry ( ai ) approach was taken to gain insight into current practices associated with care transitions and to develop insight into whether existing regulatory standards of practice for care transitions provide a sufficient underpinning to clinical practice .", ", we held a one - day workshop focused on ai philosophical approach and data collection methods .", "we began our analysis by reading through the interview notes several times to comprehend their essential features ." ], [ "three key themes emerged from the interviews in response to our questions regarding successful client transfers , including ( 1 ) flexible structures ; ( 2 ) independence and teamwork ; and ( 3 ) client- and provider - focused care .", "overall , study participants emphasized the fact that clients and families are most vulnerable when they transition between health care providers and between organizations , and we heard that nurses and other healthcare providers need to know three things to ensure safe care transitions , including ( 1 ) know your client ; ( 2 ) know your team on both sides of the transfer ; and ( 3 ) know the resources your client needs and how to get them .", "clients are placed at even more risk when there are many interruptions during the exchange of information , when there are insufficient human resources to conduct the transfer of information , when the transfer is unplanned and unprepared , when there is a lack of respect between providers , and when there is a lack of understanding about issues of client privacy and confidentiality . ", "transitions need to be timely , provide comprehensive client and family information , be customized to client needs , involve in - person exchange of information , and provide opportunities for ongoing dialogue as required .", "( pediatrics ) this theme speaks of independent and collaborative roles health care practitioners play in relation to successful handoffs ." ], [ "we heard of situations that , when facing exceptional situations , individual healthcare providers worked hard to overcome difficult dynamics and organizational policies that affect safe care transitions . in reality , the need for structures and flexibility coexists .", "we believe that when treated from a traditional mechanistic framework , structures might inadvertently impede safe transitions in care by inhibiting our ability to adapt in the dynamic , ever - changing healthcare environment . from a complexity perspective , study findings alert us to the fact that successful care transitions , and safe client and family outcomes , depend on the ways in which individual healthcare providers learn from each other and respond effectively to novel situations as they arise .", "our findings demonstrate that healthcare providers responded to client and family needs in different ways , and how the outcomes of care can be dramatically different , depending on that responsiveness . here", "given the complex and context - specific nature of transitions , and the importance of clinical judgment for client safety outcomes , we concluded that a regulatory standard of practice , designed specifically for care transitions is not necessary , nor would it likely be meaningful .", "do they use a for - granted approach when they interact with clients and with each other , seeing themselves as one person in a web of constrained and constraining relationships , not fully responsible for outcomes of care ? or do they fully engage with each client , making sense of their need and the opportunities to collaborate with other team members to become agents of possibility and transformation ? third , with respect to regulatory implication , our findings demonstrated that while professional standards of practice provide the underpinning for safe care transitions , the use of good clinical judgment in the context of each client situation is a key to successful outcomes for clients , families , and care providers ." ], [ "the present study was limited to one canadian province and the results may , to some extent , reflect contextual factors that are not shared by other national and international jurisdictions .", "however , we adopted this approach because we were most interested in hearing about how nurses and other health providers contribute to safe care transitions and learning about ways to support exemplary care . members of the study team who were new to ai expressed concerns about the positive approach at the outset of the project ; however , by the end of the project , these same individuals endorsed its use because the approach allowed us to build on current strengths and avoid the trap of only focusing on deficiencies .", "in addition , because this study is unique in its use of appreciative inquiry as a method of research , findings may be biased toward an optimistic view of care transitions .", "moreover , the project provided an excellent and unique opportunity for nurses and other health professionals to gain insight into each others ' practice environments and explore ways to uphold professional accountability in exceptional situations where innovations are required to ensure safe transitions in care ." ], [ "our findings demonstrated that exemplar transitions in care are laden with paradoxes , or the coexistence of apparent opposites , including flexible structures ; independence and teamwork ; and client and provider focus . to ensure safe and effective care transitions , nurses and other healthcare professionals need to accept the paradoxes as a normal part of their practice environment and they need to engage in relationship - rich networks which foster creativity and responsiveness . ", " examples of positive and successful transitions demonstrated universal features across settings and healthcare providers , including the involvement of the client and family in decision making and planning , comprehensive and concise client information , opportunity for questions and followup by client and family as well as health care providers , time for planning and availability of staff to execute the transfer , and interprofessional and interorganizational collaboration .", "viewed through a complexity lens , we see how the social act of call and response can lead to improved client and family outcomes , and that flexibility with regulation and standards is often required in complex sociotechnical work to make the care more efficient and adaptive to changing circumstances .", "all regulatory bodies establish expectations through policies , position statements , practice standards , guidelines and/or other documents , for how members do what they do in an effective , safe , and ethical manner .", "we conclude that the development and introduction of new regulations holds the risk of constraining professionals ' responsiveness at the point of care , thereby threatening client safety outcomes . rather than focusing on new standards of practice", ", priority needs to be given to creating conditions where nurses and other healthcare providers are free to creatively engage and respond in ways that will optimize safe care transitions ." ] ]

[ [ "positron emission tomography - computed tomography is useful for diagnosing primary and metastatic lesions of esophageal cancer .", "this case report discusses the reasons to conduct a pet / ct test and its limitations in diagnosing esophageal cancer .", "the sensitivity and specificity of a pet / ct are also relatively preferable to other diagnostic imaging tools .", "although the number of cases is few , false positives exist in which an inflammatory tumor mass and a nonspecific tumor mass are difficult to differentiate between , even when combined with other image findings . in cases of esophageal cancer ,", "positron emission tomography - computed tomographic false positives can not simply be ignored even if they appear to be due to inflammation or some other factors .", "the types of treatment and their prognosis are greatly affected if there is a metastasis or recurrence ." ], [ "the subjects of this investigation had suspected metastasis from a pet / ct which occurred before surgery of the 129 resected cases of esophageal cancer at our department from june 2010 to march 2015 .", "however , after surgery , biopsy and/or follow - up observation , only the cases that were confirmed as metastasis negative were considered to be pet / ct false positives for this assessment ." ], [ "there were 3 cases of preoperative pet / ct false positives ( table 1 ) .", "the patient is alive with no recurrence 4 years and 10 months after surgery , although the false - positive lesions in pelvic bone are still detected by pet / ct . in the case 1", "pathological finding showed poorly differentiated scc of esophagus and moderately differentiated scc of hypopharynx with a cervical lymph node metastasis ." ], [ "therefore , even when bone metastasis is suspected due to abnormal fdg accumulation after a fdg - pet , yet no bone destruction image is found in the same site by ct , then interventional radiology or a surgical biopsy should be conducted to obtain a pathological diagnosis .", "in esophageal cancer treatment , fdg - pet / ct is also used to diagnose metastases and to judge the effectiveness of treatment . especially , pretherapeutic", "in addition , fdg - pet / ct , which is a combination of a fdg - pet and a ct , improves the diagnosability even more .", "the diagnosability of lymph node metastasis using a fdg - pet for esophageal cancer is generally reported to have a sensitivity of 32% to 51.9% , a specificity of 94.2% to 100% , and an accuracy of 48% to 93% .", "dual - time - point fdg - pet has been reported to be useful in reducing this kind of false positive .", "our previous study demonstrated that the suvmax of the primary tumor was positively correlated with tumor size and vessel invasion and was positively related to the suvmax of metastic tumor . in the report , the diagnostic accuracy of pet / ct ( 87.3% ) was higher than that of conventional ct scans . when diagnosing metastatic bone tumors , the positive predictive value of bone metastasis is known to be quite high if the findings for both pet and ct match ." ], [ "this case report was on 3 patients with suspected metastasis due to a false - positive pet / ct who were later confirmed to not have metastasis .", "therapeutic decisions should be made based on appropriate and accurate diagnoses , and a pathological diagnosis should be actively introduced if necessary .", "the metastases were originally suspected after conducting a pet / ct before surgery to treat esophageal cancer or during the postoperative course .", "conducting a pet / ct is useful when diagnosing esophageal cancer metastasis , but there should be an awareness of the possibility of false positives ." ] ]

[ [ "the purpose of the present study was to measure the three - dimensional ( 3d ) movement of 1st molars after using this newly designed distalizing appliance .", "traction between tads in the palatal interdental area and a tpa can produce direct distalization force that travels through the center of resistance of molars ( figure 1 ) .", "moreover , these tads can also control the mesiodistal axis of the molar via manipulation of the line of action.22 we have introduced a new appliance using palatal miniscrews \" mimi - implant - aided ( mia ) in the interdental area between the 1st molar and 2nd premolar root and a trans - palatal arch ( tpa ) to overcome some of the mechanical shortcomings of previous appliances , in contexts including anterior protrusion , extrusion of posterior teeth , and tipping of molar teeth ( mia - tpa ) ." ], [ "the main inclusion criterion was angle class ii malocclusion of no more than one cusp on each side .", "the angles between the incisive papilla and the distopalatal and mesiobuccal cusps of the 1st maxillary molars were measured to evaluate the rotation of maxillary molars1 ( figure 2 ) .", "the palatal rugae possesses unique characteristics , and as it tends to exhibit reasonable stability during growth , it may serve as a suitable reference point for longitudinal cast analysis.23 as the patients in the current study were not in an active growth period and no potential incisor movement was anticipated during the distalization period , as in nalcaci et al.,1 the distance from the central point of the incisive papilla to the mesiopalatal cusp of the 1st maxillary molars was used to measure distalization .", "the final arch wire was 0.018-in stainless steel . a cone - beam computed tomography ( cbct ) scan ( newtom 3 g ; quantitative radiology , verona , italy ) was performed to evaluate the precise position of mini screws relative to adjacent teeth and the direction of the force relative to molar teeth .", "the sample group consisted of 26 patients ( 22 females , 4 males ) with an average age of 19.8 6.3 years ( range 12 - 36 years ) at the beginning of treatment ( table 1 ) .", "digital model analysis of molars was used to evaluate changes in the 3d position of the maxillary molars ." ], [ "the palatal rugae possesses unique characteristics , and as it tends to exhibit reasonable stability during growth , it may serve as a suitable reference point for longitudinal cast analysis.23 as the patients in the current study were not in an active growth period and no potential incisor movement was anticipated during the distalization period , as in nalcaci et al.,1 the distance from the central point of the incisive papilla to the mesiopalatal cusp of the 1st maxillary molars was used to measure distalization .", "the angle between this line and a line drawn parallel to the occlusal plane was measured on right and left 3d sagittal view . in 3d axial view , lines between the helix and the miniscrews on the right and left sides were drawn , and the angle between those lines ( axial angle ) was measured ( figure 4 ) .", "the angles between the incisive papilla and the distopalatal and mesiobuccal cusps of the 1st maxillary molars were measured to evaluate the rotation of maxillary molars1 ( figure 2 ) .", "interocclusal space at the mesiobuccal , distobuccal , and mesiopalatal cusps of the 1st maxillary molars was evaluated by occlusion inspection , and maestro 3d scanner and software was used to evaluate vertical movement . after putting the casts in the maximum intercuspal position ,", "the spaces between the maxillary 1st molar cusps and the antagonist tooth at t1 and t2 were measured via a 0.5-mm interval scale with a color coded tool ( figure 3 ) . for cbct analysis", ", digital imaging and communications in medicine ( dicom ) files were imported to a dolphin 3d 11 ( dolphin imaging , chatsworth , ca , usa ) .", "the distances between the mesiopalatal cusps of the left and right molars were measured to evaluate intermolar width ." ], [ "measurements were repeated one month after the initial measurements , and the reliability of the measurements was calculated via the intraclass correlation test .", "pearson 's correlation was used to evaluate the relationships between cbct parameters and digital cast parameters . statistical package for the social sciences ver . 13.0 ( spss inc . ,", "the paired t - test was used to compare measurements acquired before and after distalization in a digital cast . a probability of p < 0.05 was deemed to indicate statistical significance .", "reliability was between 79.7 and 97.0 for linear measurements , and between 93.8 and 96.6 for angular measurements ." ], [ "the mean duration of distalization was 6.8 2.8 months ( range 2 - 14 months ) , thus the average rate of distalization achieved via the method utilized in the current study was 0.4 0.2 mm / month .", "the examination of vertical movement of three cusps of the maxillary molars showed relative molar intrusion that was statistically significant , except in the left mesiopalatal cusp ( table 2 ) .", "maxillary 1st molars were slightly rotated mesially around the palatal root after distalization , though the amount of rotation was not statistically significant ( this rotation is shown with a minus sign in table 2 ) .", "maxillary 1st molars were moved distally an average of 2.3 1.1 mm , and the difference between the right and left sides was not statistically significant ( p = 0.63 ) .", "the mean intermolar width increase was 2.9 1.8 mm ( range 0.6 - 6.8 mm ) ." ], [ "excessive contact between the tpa and the miniscrew was the probable cause of screw failure in these cases .", "many studies on intraoral maxillary molar distalization without patient cooperation have been performed , in order to solve the patient compliance problem associated with extraoral distalization appliances.110111220222425262728 in the present study , maxillary 1st molars were distalized via mini - implant - aided tpa . in mia - tpa ,", "orthodontists are frequently faced with mild to moderate class ii molar and canine relationships that they prefer not to treat via the extraction of premolars , and for which treatment via auxiliary methods is often unsatisfactory due to insufficient patient compliance .", "direct traction from elastic modules spanning from a miniscrew to a tpa helix is used to achieve molar distalization .", "the intermolar change can provide a clear determination of both the distal and buccal movement of maxillary molars according to best available anatomical reference points . applying a distal force to maxillary molars moved them in three dimensions . with the device used in the current study" ], [ "the mia - tpa is an appliance that can achieve absolute anchorage , and successfully drive maxillary 1st molars distally ." ] ]

[ [ "acute liver failure ( alf ) is a rare but life - threatening illness which occurs mostly in young adults without any known underlying liver disease [ 1 , 2 ] . in the united states ,", "we report a case of successful orthotopic liver transplantation ( olt ) in a 67-year - old female who presented with ebv - associated alf .", "it may cause moderate and transitory increase of liver enzymes ; however , in rare cases , severe liver injury and even fatal alf may occur .", "the most common cause of alf is acetaminophen overdose ( 39% ) but in 13% of cases , the causes are indeterminate .", "epstein - barr virus ( ebv ) is a dna virus associated with infectious mononucleosis ( i m ) in children and young adults ." ], [ "the patient is presently doing well 6 months after liver transplantation with no evidence of clinical ebv infection or lymphoproliferative disease .", "a 67-year - old woman with bilateral osteoarthritis of the knee , hypothyroidism and recurrent deep vein thrombosis presented with 3 weeks of fatigue and a 1-week history of jaundice .", "a review of the liver biopsy 5 days prior to admission showed about 25% hepatic parenchyma necrosis with bridging necrosis ( fig .", "antinuclear antibody , anti - mitochondrial antibody and anti - smooth muscle antibody were negative . the patient was initially diagnosed with alf possibly , secondary to diclofenac use , because she had begun to take diclofenac potassium 50 mg twice daily since 5 months ago .", "she was given midodrine and octreotide and underwent hemodialysis for hepatorenal syndrome . despite multiple transfusions of ffp , her coagulopathy worsened , and her inr was 3.7 the following day .", "she was started on intravenous acyclovir immediately after the diagnosis of ebv infection , and later she was switched to oral acyclovir which was administered for 3 months ." ], [ "we describe a case of alf - associated with ebv infection in a previously healthy elderly woman that underwent successful emergent liver transplantation .", "this is the first case of ebv reactivation - associated alf in a healthy elderly patient .", "fulminant liver failure , is a sudden and severe hepatic injury in patients without previous liver diseases .", ", our case demonstrates that ebv infection or reactivation may be under - recognized as a cause of alf ." ] ]

[ [ "the purposes of this study were to measure the length of the central myelin , especially from root detach point to transitional zone and determine histological structures of central myelin of facial nerve .", "cranial nerves were composed of two different histological portions , glial and non - glial portion .", "skinner12 ) reported the extent of glial out growth into the various cranial nerves and glial out spread of facial nerve was extended as far as 2.6 mm in length from the origin of brain stem . in general ,", "recently , some authors proposed to replace the term of rez by root exit point ( rexp ) , root detach point ( rdp ) , and root exit zone ( rexz ) in detail13 ) .", "root exit zone or root entry zone ( rez ) of cranial nerves means the area nerves come from the brainstem .", "the transitional zone refers to the junction between glial portion and the non - glial peripheral portion ." ], [ "twenty brain stems were obtained from formalin embedded cadavers . the 12 men and 8 women of cadavers ranged in age from 32 to 78 years ( mean , 58 years ) . during the brain", "twenty three facial nerves could be examined properly . to make a facial nerve - brainstem tissue block", "stems were served , care should be taken to preserve the cisternal segment of facial nerve .", "usually to correct for the shrinkage error during fixation , occulomotor nerve of same specimen was used as a standard .", "but we did not calculate the percentage of facial nerve shrinkage because of being used pre - fixed specimens with formalin ." ], [ "the outermost membrane surrounding the brain stem , glial limiting membrane , continues to the central myelin could be visible .", "2 ) . glial outgrowth from the brain stem , central myelin , ends in dome or cone formation .", "the mean thickness of glial membrane of central myelin was 66.5 um ( 40 - 110 um ) at proximal and 7.4 um ( range of 5 - 10 um ) at distal ( table 1 ) .", "with the h&e staining , the shape of facial nerve was easily determined ( fig .", "special staining methods , such as pas and gfap , could be clearly distinguished the facial nerve into peripheral and central myelin . peripheral myelin was stained dark blue with pas staining and central myelin was stained dark brown with gfap ( fig ." ], [ "the glial sheath of central myelin may act as a barrier of the nerve fiber from vascular compression .", "the mechanism of hemifacial spasm is thought that thinning or defect of neural sheath of facial nerve because of vascular compression may result in developing cross talking of neural transmission4,9 ) .", "the cause of hemifacial spams is generally known as that facial nerve compressed by blood vessels located at the rez .", ", rez means the area nerve comes from the brainstem and transitional zone refers to glia - schwann cell border . the term of rez was defined by jannetta as a junctional area between central and peripheral myelin6 ) .", "glial portion of the cranial nerve , central myelin , is composed of fibrillary astrocyte and oligodendroglia cells12 ) .", "there is an outgrowth of glia cells , astrocyte and oligodendroglia , along the cranial nerve trunks and the extent of glial outgrowth varies in different nerves ." ], [ "they have proposed the use of terms root exit point ( rexp ) , rdp ( medial detach point ) and transitional zone instead of rez . and they stressed the rdp appears to be a good landmark for the microvascular decompression surgery .", ", rez means the area nerve comes from the brainstem and transitional zone refers to glia - schwann cell border . the term of rez was defined by jannetta as a junctional area between central and peripheral myelin6 ) .", "many authors used the terms of rez and transitional zone interchangeably1,3,11 ) . in a recent study , tomii et al.13 ) described the transitional zone as the region where the myelin sheath is composed of both central glial and schwann cell myelin .", "there is no clear description of the relationship between the rez and the transitional zone . in the strict sense" ], [ "we measured the distance from medial detach point of brain stem to the most distal glial segment of facial nerve .", "the exact length of central myelin of facial nerve is difficult because of its irregular distal margin .", "skinner12 ) reported that the glial outspread in the facial nerve extended as far as 2.6 mm from the plane of superficial origin .", "adams1 ) described that the transitional zone is only 1 to 3 mm in length .", "jannetta6 ) also reported the distance to the peripheral boundary of the rez was 0.5 to 1 cm in the fifth , seventh , and ninth cranial nerves . in 2003 ," ], [ "we observed that the glial limiting membrane extending from the outermost layer of brain stem , strong stained with gfap , surrounds the central myelin .", "the glial sheath of central myelin may act as a barrier of the nerve fiber from vascular compression .", "glial portion of the cranial nerve , central myelin , is composed of fibrillary astrocyte and oligodendroglia cells12 ) .", "we called the layer closing the central myelin as glial sheath like epineural sheath of peripheral nerve .", "the cause of hemifacial spams is generally known as that facial nerve compressed by blood vessels located at the rez ." ], [ "our study shows the length of medial rez is mean 2.6 mm ( range of 1.6 - 3.5 mm ) and the rez is covered by glial sheath continued from glial limiting membrane of brain stem ." ] ]

[ [ "recent work has underscored the additional importance of cognitive impairment as a key factor contributing to both falls and freezing ; falls are an issue in demented patients in particular .", "preventing falls is generally perceived as being difficult , but is not impossible . given the complex multifactorial nature of falls and the experience in elderly non - parkinsonian populations , a multidisciplinary approach appears preferable , but for patients with pd this strategy is not yet backed by scientific evidence .", "crucial elements in the therapeutic approach include optimizing pharmacotherapy - increasing pd medication for dopa - sensitive signs , and stopping sedative drugs - and tailored physiotherapy , based on evidence - based practice guidelines . here , we highlight a few important new developments in this field .", "falls are both common and debilitating in patients with parkinson 's disease ( pd ) .", "there is an increasing awareness that freezing of gait - a sudden and episodically occurring inability to generate effective forward stepping movements - is one of the leading causes of falls , presumably because patients are caught by surprise due to the often unexpected nature of freezing events .", "survival is reduced once falls have occurred , although a recent report failed to identify a relationship between falls and mortality risk in pd .", "falls are also important for the public health system , as the costs associated with falls and fall - related injuries are enormous ." ], [ "recent work points to a possible role for cholinesterase inhibitors in the treatment of gait and balance deficits , both in pd and in alzheimer 's disease , given that many axial motor deficits may result from misbalance between central cholinergic and dopaminergic systems .", "future randomized controlled trials will look into the ( cost ) effectiveness of exercise to reduce falls . there is a growing body of literature on the use of treadmill training for gait rehabilitation in patients with neurologic disorders in general and for patients with pd in particular .", "it has become clear that stereotactic deep brain surgery should be reserved for patients whose gait and balance deficits are still levodopa - responsive pre - operatively .", "another interesting new development is the use of robotics , which can assist pd patients in making medio - lateral anticipatory weight shifts in preparation for taking a step .", "the best prediction was reached by combining disease - specific measures ( such as pd severity and freezing of gait severity ) with balance measures ( such as the occurrence of symptomatic orthostatic hypotension , the tinetti total score , and the extent of postural anterior - posterior sway ) . however , even this combination attained a sensitivity and specificity for predicting falls of only around 80% . including cognitive measures that are more specific may further improve these predictive scores , but this remains to be examined ." ], [ "the quest should not stop when one causative factor has been found because falls are typically multifactorial in origin . a recent prospective study in 101 patients with early - stage pd assessed", "specific attention should be paid to fear of renewed falling as this is common in pd .", "particular emphasis should be placed on testing for freezing of gait - using a series of provoking tests , including rapid 360 degree turns on the spot - and for frontal executive dysfunction .", "the best prediction was reached by combining disease - specific measures ( such as pd severity and freezing of gait severity ) with balance measures ( such as the occurrence of symptomatic orthostatic hypotension , the tinetti total score , and the extent of postural anterior - posterior sway ) . however , even this combination attained a sensitivity and specificity for predicting falls of only around 80% . including cognitive measures that are more specific may further improve these predictive scores , but this remains to be examined .", "fear of falling is not only a risk factor for renewed falls , it may also lead to secondary immobilization with all its related adverse consequences ." ], [ "most balance deficits are resistant to dopaminergic medication . however , gait problems - including freezing of gait - can improve with dopaminergic medication , although doses that are higher or more frequent than those typically needed to increase hand functioning may be required .", "recent work points to a possible role for cholinesterase inhibitors in the treatment of gait and balance deficits , both in pd and in alzheimer 's disease , given that many axial motor deficits may result from misbalance between central cholinergic and dopaminergic systems ." ], [ "it has become clear that stereotactic deep brain surgery should be reserved for patients whose gait and balance deficits are still levodopa - responsive pre - operatively .", "several studies are comparing bilateral stimulation of two different targets , namely the subthalamic nucleus ( stn ) and the internal globus pallidus .", "the initial results indicate that both approaches are effective in providing short - term relief of motor symptoms , but one study suggested internal globus pallidus stimulation may offer better long - term outcomes for gait and balance deficits .", "this difference was not evident in the largest study , although falls after a 2-year follow - up tended to be more common after stn stimulation , but this requires more study . in particular , stn stimulation has been associated with a worsening of gait and balance deficits , not only in the immediate postoperative phase , but also several years after follow - up .", "the pedunculopontine nucleus has been studied as a promising new target , specifically for gait and balance deficits , but so far the results have not been very impressive .", "adjusting the stimulation parameters ( e.g. , markedly lowering the stimulation frequency ) may be helpful in such patients ." ], [ "the evidence - based guidelines on physiotherapy for pd were recently updated , providing a menu of treatment modalities to improve mobility and reduce falls . examples of evidence - based physiotherapy strategies include cueing techniques , cognitive movement strategies , and the use of exercise . rhythmic auditory or visual cues can improve gait in pd , including freezing of gait .", "future randomized controlled trials will look into the ( cost ) effectiveness of exercise to reduce falls . there is a growing body of literature on the use of treadmill training for gait rehabilitation in patients with neurologic disorders in general and for patients with pd in particular .", "a large cluster - randomized trial showed that a community - based professional network with trained expert physiotherapists improved the quality of physiotherapy care and reduced health care costs , but without health benefits for patients .", "new inventive cueing approaches include walking glasses with different patterns of visual and auditory stimulation and mental singing while walking .", "another interesting new development is the use of robotics , which can assist pd patients in making medio - lateral anticipatory weight shifts in preparation for taking a step ." ], [ "asking about falls and their impact on daily functioning should be a standard part of the evaluation of patients with pd . while awaiting further evidence , neurologists should consider installing a multidisciplinary team approach to tackle the vexing problem of falls in patients with pd .", "fear of falling must be addressed , and immobilization must be avoided as long as independent movements can still be made reasonably safely .", ", the goal should be to at least reduce falls or perhaps prevent them altogether , restore mobility and independence , and thereby help to maintain the quality of life for patients with pd .", "the multidisciplinary team should ideally consist of trained and experienced professionals who treat large numbers of patients . using this integrated approach", "management involves a systematic search for risk factors for falling , and a subsequent multifactorial approach aimed at eliminating or alleviating all patient - related and environmental risk factors for falling .", "apart from optimizing dopaminergic medication , cholinergic therapies are now beginning to enter the field of play as well ." ], [] ]

[ [ "we describe the discovery and characterization of a novel \n class of selective non - lbp true ", "the biological \n data obtained both on target with time - resolved fluorescence resonance \n energy transfer ( tr - fret)/fluorescence polarization ( fp ) assays and \n in cellular pca models demonstrate the non - lbp antagonist activity \n of the series and an alternative mechanism of inhibition , furnishing \n a new class of nonpeptidic , small molecule ar : coactivator selective \n disruptors as leads for the development of novel treatments for prostate \n cancer .", "antiandrogens , characterized \n by full ar antagonism in inhibiting the recruitment of coactivators \n and lacking intrinsic partial agonistic properties .", "prostate cancer ( pca ) is one of the major \n causes of cancer death in men worldwide .", "mechanistically , \n these compounds are totally differentiated from the recent description \n of true lbp antiandrogens like mdv3100 and rd162 , while their selectivity and druglike nature underpin the potential \n of a non - lbp intervention strategy in advanced prostate cancer resistant \n to classical therapy " ], [ "the cocrystallization of the ar lbd bound with \n dht in the presence of the fxxlf peptide ( pdb i d 1t7r ) provided the structural basis of the af-2 interaction for \n docking studies . virtual screening and identification of diarylhydrazide \n scaffolds . (", "subsequently , a second site - derived \n pharmacophore model was advanced based on the specific characteristics \n of the androgen receptor af-2 region , which demonstrates known selectivity \n toward the fxxlf coactivator motif ( figure 1b ) .", "a virtual ( computational ) screen \n of six vendor compound databases ( see experimental \n section ) was performed through a combination of 3d pharmacophore \n generation and docking .", "seven x - ray structures of coactivator peptide \n bound ar were used to define key ligand - derived pharmacophoric features \n of the most represented motifs occurring in known ar coactivators . initially ,", "we undertook to profile the selectivity of these compounds for \n ar over other members of the same phylogenetic branch of the steroidal \n nuclear receptor subfamily .", "a ) a series of coactivator peptides cocrystallized in \n the af-2 groove was employed ; for illustrative purposes we present \n the fxxlf coactivator motif from pdb entry 1t7r .", "was found to antagonize cpa partial agonist \n activity ( measured as secreted psa levels in the cellular media in \n an elisa experiment ) , suggesting its potential benefit in combination \n therapy for advanced stages of prostate cancer ( figure 6c ) . to further challenge this hypothesis ," ], [ "alternative \n ar inhibitors are therefore needed in the treatment of pca . in this \n study , we demonstrate the successful implementation of a virtual screening \n approach in the identification of small molecule ar modulators , where \n the structural motif of ar coactivators was included in a 3d pharmacophore . \n", "classical antiandrogen therapy is known \n to have limited beneficial effects in hormone - insensitive pca .", "we report the discovery , identification , and characterization of a \n novel series of diarylhydrazide non - lbp - binding antiandrogen compounds , \n with demonstrated ability to displace ar coactivators and with established \n potency in ar - dependent prostate cancer cell lines ." ], [ "through application of virtual screening \n methodologies , we present and characterize novel diarylhydrazide scaffolds \n as true antiandrogens displacing ar coactivator interaction \n and having a full antagonistic profile on ar ( both wt and t877a ) , \n partial antagonistic profile for pr , and selectivity for the other \n members of the nr-3 family ( gr , er- , and er- ) .", "coactivator \n interface , to understand the basis of selectivity , and to further \n guide rational drug design in the search of other novel scaffolds \n directed at this interface .", "the initial small molecule non - lbp true ar modulators provided by \n this study will be used to further characterize the ar " ], [ "a virtual screen was designed to \n select compounds mapping onto the peptide binding surface ( af2 ) of \n the ar receptor , based on an ensemble of documented x - ray crystal \n structures ( pdb i d 1t73 , 1t74 , 1t76 , 1t79 , 1t7f , 1t7 m , 1t7r , and 1t7 t ) .", "the virtual molecules were overlaid \n on and compared to the generated pharmacophore of the active ligands , \n and those molecules that compared favorably were advanced for additional \n virtual screening and scoring . the fast rigid exhaustive docking ( fred ) software as implemented in openeye scientific s \n package was used to exhaustively examine all possible poses within \n the protein site , filtering for shape complementarity and scoring . \n", "these \n pharmacophore models were then applied for in silico screens of small - molecule \n commercial libraries to identify compounds that resemble the active \n principle of the starting peptides .", "p3018 ) was \n used to investigate the binding of the test compound to the lbp site , \n occupied by a high - affinity fluorophore ligand ( fluormone ) .", "thirty - seven compounds were purchased and four small molecules were \n selected for optimization and characterization studies based on their \n improved on - target activity determined by tr - fret .", "all screening compounds \n described in this work were purchased as commercial samples from specs \n nv ." ] ]

[ [ "during the last years tyrosine kinase inhibitors ( tkis ) have changed the natural history of metastatic non - small - cell lung cancer ( nsclc ) harboring epidermal growth factor receptor ( egfr ) mutations .", "to our knowledge , few cases of lcnec with egfr gene mutation have been described up to now , and only one case was treated with gefitinib , with a good response [ 7 , 8 ] .", "not surprisingly , the use of tkis was correlated with a higher response rate , a longer progression - free survival and a better quality of life in patients with advanced nsclc activating egfr mutation .", "eight important studies were conducted to evaluate the efficacy and tolerability of tkis on advanced nsclc in comparison with standard platinum - based chemotherapy ." ], [ "were increased , it was not possible to identify the primary site of localization of the tumor and to reach a definitive diagnosis . given the rapidly progressive impairment of her clinical conditions and performance status , we administered an empirically not targeted chemotherapy with gemcitabine 1,000 mg / m die 1 and oxaliplatin 100 mg / m die 2 q 2 weeks although we did not yet have definitive histopathological results .", "the patient reports a good quality of life and no relevant side effects ( skin toxicity grade 1 ) have been registered .", "however , since a further deterioration of her clinical condition was observed , a biopsy was repeated in order to have an additional sample for molecular analysis .", "a restaging total body ct scan showed a significant improvement of disease , with a partial response > 50% ." ], [ "lcnec is a rare tumor which is usually treated with cisplatin - based chemotherapy as sclc as it shares many characteristics with it . usually , the administration of tkis is considered only for advanced lung adenocarcinoma because the most important studies demonstrating higher activity of tki , in comparison with standard platinum - based chemotherapy , were conducted in patients affected by nsclc with egfr mutations .", "we report the case of a patient affected by lcnec carrying all of the predictive characteristics associated with egfr mutation ( caucasian , female , never - smoker ) .", "when the patient came to our attention she was very symptomatic , so in an attempt to reach a better and faster response , we decided to test egfr mutational status . strikingly , the mutation was present , and we were allowed to administered gefitinib , obtaining an impressive and objective response .", "the prognosis of this tumor with standard chemotherapy is poor , thus we need to evaluate alternative diagnostic strategies such as the investigation of egfr mutational status in order to explore new effective treatments .", "some features are associated with a higher possibility that egfr mutations are present in nsclc .", "the research of egfr mutations is not performed routinely on lcnec since this mutation is not commonly present in this subtype ." ], [] ]

[ [ "residual rv outflow tract obstruction with accompanying pulmonary regurgitation is the most frequently reported sequela after initial surgical correction of tof .", "we herein report a rare case of subaortic stenosis in association with a previous tof surgical repair that was not considered to be a differential diagnosis .", "complications related to surgical repair of tof are clinically relevant and include pulmonary regurgitation , residual obstruction of the right ventricular ( rv ) outflow tract , rv systolic dysfunction , and arrhythmias . among these ,", "tetralogy of fallot ( tof ) accounts for approximately 5% to 7% of all cases of congenital heart disease .", "therefore , a systolic murmur that is audible over the base of the heart is frequently interpreted as a residual rv outflow tract lesion . however , this is not always true .", "discrete subaortic stenosis is generally thought of as a disease of children or young adults ( < 25 years of age ) and is thus rarely reported in subjects older than 25 years , particularly in association with tof ." ], [ "a 29-year - old woman presented for a routine check - up of surgically corrected congenital heart disease . at 7 years of age , she had undergone surgical repair of tof with excision of the infundibular stenosis and closure of a 10-mm ventricular septal defect .", "the patient underwent resection of the subaortic membrane and myomectomy of the lv outflow tract along with aortic valve commissurotomy .", "transthoracic and transesophageal echocardiograms both demonstrated severe subaortic stenosis due to a subvalvular membrane , on which a mobile mass - like structure that was suspicious of a vegetation was noted ( fig ." ], [ "transthoracic and transesophageal echocardiography can assist differentiation of the rv from the lv outflow tract obstruction .", "subaortic stenosis is strongly associated with other congenital heart defects ; however , subaortic stenosis in association with tof , especially in women , is extremely rare . according to a medline database review of the last 30 years", "although subaortic stenosis is the second most - common form of lv outflow tract obstruction , it is predominantly found in children or adolescents [ 4 - 8 ] ." ] ]

[ [ "the current study investigates the ability of crp and tnf- to induce papp - a expression in the pbmcs of healthy volunteers .", "pregnancy - associated plasma protein - a ( papp - a ) is a metzincin metalloproteinase primarily produced by the placental syncytiotrophoblast during pregnancy .", "several studies have shown a similar role for papp - a in modulating site- and event - specific igf signaling during injury repair processes .", "furthermore , inhibitor experiments have been designed to explore the underlying intracellular signaling pathways involved in papp - a expression .", "the focus of these studies is nuclear factor- ( nf- ) b pathways , a major pathway associated with cytokine stimulation in various cell types ." ], [ "resultant solutions were added to cultured pmbcs at defined time intervals ( 2 , 8 , 16 , 24 hours ) and concentrations ( crp : 5 , 10 , or 20 mg / l ; tnf- : 25 , 50 , or 100 ng / ml ; bay11 - 7082 : 20 m ) in the absence or presence of actinomycin d ( 1 g / ml ) , as further described in the following sections .", "the relative intensity of bands of interest was expressed as the ratio to -actin mrna bands . for cell lysates , cells were washed twice with ice - cold pbs and lysed in ripa buffer .", "peripheral blood was collected from the forearm vein of healthy volunteers enrolled in the current study . for each experiment ,", "resultant cells were washed 3 times with pbs and subsequently resuspended in rpmi 1640 ( gibcobrl , grand island , ny , usa ) supplemented with 10% fetal calf serum ( gibcobrl , grand island , ny , usa ) , penicillin ( 100 u / ml ) , and streptomycin ( 100 g / ml ) . cells were then cultured for 24 hours in plastic dishes at 37c in a humidified atmosphere of 5% co2 . upon observation of subconfluent growth , the medium was replaced with fresh medium .", "the pharmacological agents recombinant human tnf- ( perprotech , rocky hill , ct , usa ) , crp , actinomycin d , and bay11 - 7082 ( sigma chemicals , deisenhofen , germany ) were dissolved into solution according to the manufacturer 's instructions .", "human pbmcs were isolated from 30 ml fresh blood samples obtained from healthy volunteers by ficoll - paque ( amersham bioscience , uppsala , sweden ) centrifugation .", "rabbit polyclonal antibodies against human papp - a ( 1 : 1000 , abcam systems , cambridge , usa ) were used as the primary antibody .", "the assay was calibrated using recombinant papp - a calibrated against the world health organization 's international reference preparation 78/610 for pregnancy - associated proteins , by definition containing a papp - a concentration of 100 " ], [ "the basic mechanism by which nfb is activated is through phosphorylation of intrinsic inhibitors , with the ib , subsequently freeing nfb to translocate into the nucleus where it regulates gene expression .", "it is well known that the nfb pathway is the critical mediator of prooxidant stimuli , such as inflammatory cytokines .", "these results showed that crp or tnf- was responsible for new protein synthesis of the papp - a protein .", "20 mg / l ) or tnf- ( 100 ng / ml ) significantly increased papp - a mrna expression , protein expression , and concentrations in culture supernatants . to confirm the role of nfb activation , bay11 - 7082 , which inhibits inducible phosphorylation of ib , was shown to effectively inhibited crp and tnf--stimulated papp - a expression ( figures 4(a ) , 4(b ) , and 4(c ) ) ." ], [ "the current study indicates that papp - a expression in human pbmcs may be regulated by crp and tnf- through the nf-b pathway , a mechanism that may play a critical role in increases in serum papp - a levels during acute coronary syndrome ( acs ) .", "based on this observation , it is possible that the biological consequence of crp- and tnf--induced papp - a expression in human pbmcs was enhanced igf - i bioactivity mediated by papp - a proteolysis of igfbp-4 , thus contributing to the progression of both coronary atherosclerosis and restenosis .", "the current results , however , provide the fundamental mechanistic groundwork for further understanding of the entire mechanism associated with cytokine regulation of papp - a expression and igf bioavailability .", "furthermore , crp and tnf- were indicated to be potent stimulators of papp - a gene expression and protein secretion in human pbmcs , suggesting a link between the increase in local inflammatory cytokine production and papp - a during acs .", "while further studies of the in vivo effects in acs patients will be required to confirm these results , these findings suggest that serum papp - a , hscrp , and tnf- levels may be significantly higher in acs patients than in patients with stable angina pectoris and that increasing papp - a mrna levels in patients with acs may also have a positive association with serum hscrp and tnf- mrna expression .", "serum papp - a levels increase in patients with acs , indicating that papp - a may also be a marker of adverse events [ 1618 ] ." ] ]

[ [ "this study sought to identify the factors contributing to patients ' satisfaction , shed more light on the burden of patients ' dissatisfaction with the consultation in our environment , and help devise strategies for practicing physicians to strive for an improvement in the overall patient care in our cultural context .", "the findings would provide some of the information needed to further fill the knowledge gap about our patient needs in our environment and highlight the need to teach the consultation process at both undergraduate and postgraduate medical training .", "this study comes from a background where patient awareness of their opportunities in the patient doctor encounter is still in its early days , and thus this study brings to the literature a unique perspective of the patients ' views from this environment .", "the core activity in primary care is the consultation irrespective of whether patients consult for cure , services , counseling , prevention , or care .", "there is an increasing interest in the study of the consultation process and patients ' satisfaction with it .", "a widely accepted model views the consultation as a dialogue involving elements of negotiation to create a common reality to which agenda setting is paramount . in the medical consultation" ], [ "the university of calabar teaching hospital is a tertiary hospital located within calabar metropolis , which lies along latitude 4 , 58 north of the equator and longitude 820 east of the greenwich meridian .", "this study was conducted in the general outpatient clinic ( gopc ) of the university of calabar teaching hospital , ( ucth ) calabar .", "the general outpatient clinic ( gopc ) is situated at the permanent site and has fourteen outpatient consulting rooms in which about 1014 doctors ( family physicians or resident doctors in family medicine ) consult from 8 am4 pm on a daily basis .", "three consulting rooms are for consultants , three for doctors dedicated to the hiv clinic , one for consultancy patients , one for patients who are staff , and six consulting rooms are for outpatient consultation by other doctors .", "margaret 's annex , maternity annex , the permanent site , and the comprehensive health centre ( chc ) okoyong .", "data generated in the study was analyzed using the epi info software for analyzing medical data from the centre for disease control , atlanta , georgia , usa .", "the general practice assessment questionnaire was developed in the united kingdom and used to study certain components of the consultation ." ], [ "the patient 's assessment of time spent in the consultation was shown to have a statistically significant influence on the patients satisfaction with the consultation ( p < 0.001 ) .", "seventy - eight percent of the patients who participated in the study and perceived that the encounter had made it possible to cope with the illness were satisfied with their encounter ( table 2 ) . a good majority of the patients perceived that their ability to cope with the illness after the visit influenced the patients ' satisfaction with the encounter ( p < 0.001 ) . ", "this table also shows that the patients preference for a particular physician did not statistically influence the patients satisfaction with the consultation ( p > 0.05 ) .", "the age distribution of the respondents varied with the highest proportion being young adults aged 2640 years ( 44% ) , adolescents aged 1825 years ( 34% ) , middle - aged persons aged 4160 years ( 18% ) , and elderly patients aged 60 + 9 ( 4% ) , table 1 ." ], [ "a patient 's ability to maintain health after a consultation would be addressing one of the core issues in family medicine by promoting prevention of illnesses .", "this study demonstrates a statistically significant effect of a patient 's ability to cope with his illness on his / her satisfaction with the consultation ( table 2 ) .", "however , the study has shown that , despite the various factors that are considered to encourage client satisfaction at primary care consultation , a few of such factors contributed to end of consultation satisfaction in our environment .", "the effect of managed care in this study can not be discussed owing to the low number of patients who were using health care insurance , but studies in the united states have demonstrated that managed care affects neither the perception of time used in the consultation nor patients ' satisfaction with it .", "it is recommended that the physician - related factors that influence the doctor - patient encounter should be further studied .", "teaching of consultation process must take these factors into consideration . to further address effort towards improving patient satisfaction rates in the study centre ," ] ]

[ [ "the aim of this study is to assess the possible reduction in the extent of acute kidney injury after administration of eugenol in an experimental model of acute pancreatitis .", "acute pancreatitis is an inflammatory intra - abdominal process , which in approximately 1520% of patients presents in a severe form , with a gradual establishment of multiple organ dysfunction or local complications , including necrosis , pseudocyst , and abscess .", "severe acute pancreatitis is a condition associated with high mortality , which is characterized by a complex and incompletely understood pathophysiological mechanism [ 2 , 3 ] .", "the prevention of acute kidney injury can be a useful strategy in the prevention of the morbidity and mortality associated with acute pancreatitis .", "it has many pharmacological properties which are mainly analgesic , anti - inflammatory , antioxidant , and vasodilatory action , while it has been shown to ameliorate kidney injury in a model of gentamycin - induced nephrotoxicity ." ], [ "the animals were randomly assigned in 3 groups : sham ( n = 20 ) , control ( n = 46 ) , and eugenol ( n = 40 ) .", "this was achieved with the admixture of pure eugenol in a corn oil solution in a concentration of 1.5 mg eugenol / ml .", "eugenol was administered by a nasogastric catheter in a dose of 15 mg / kg , while the sham and control groups received corn oil solution without eugenol .", "euthanasia was performed at a predetermined time for each animal with the use of ketamine ( narcetan ; vetoquinol , buckingham , uk ) 0.30.6 ml and xylazine ( rompun ; bayer , uxbridge , uk ) 0.10.3 ml , followed by a midline laparotomy and exsanguination of the abdominal aorta .", "106 male wistar rats , aged 3 - 4 months and weighing 220350 gr , were used in this study .", "the results were graded as negative ( 0 ) for < 10% of stained cells , low ( 1 ) for > 10% and < 30% of cells stained , moderate ( 2 ) for > 30% and < 70% cells stained , and high expression ( 3 ) for > 70% cells stained ( table 1 ) .", "immunohistochemical staining was applied to detect the possible expression of inflammatory cytokines like il-6 , tnf- , and myeloperoxidase .", "serum samples for measurement of urea and creatinine as well as specimens from both kidneys for histopathological examination were acquired ." ], [ "eugenol administration resulted in lower serum levels of urea and creatinine especially at the 48- and 72-hour time points , compared to the control group .", "urea and creatinine levels were higher for both the eugenol and control groups , when they were compared to the sham group ( figure 4 ) .", "eugenol administration lowers hyperemia and dilation of renal parenchyma capillaries and the difference was statistically significant for the 48 and 72 hour time points and for the whole sample .", "the difference between the eugenol and control groups is apparent at 48 and 72 hours after induction of pancreatitis ( figures 1 and 2 ) .", "there was a statistically significant difference between the eugenol and control groups 72 hours after induction of pancreatitis , while both groups exhibit higher tnf- expression than the sham group .", "there was no statistically significant difference between the eugenol and control groups for mpo expression , although there was a trend toward higher expression for the control group after 72 hours ." ], [ "the results of this study suggest that eugenol attenuates the intensity of the histopathological changes and the expression of tnf- and mpo in the renal parenchyma , while lowering the values of serum urea and creatinine when administered in a rat acute pancreatitis experimental model .", "in conclusion , the administration of eugenol in a rat model of acute pancreatitis was protective for the kidneys in our experimental model .", "to evaluate the extent of kidney injury , we decided to evaluate serum urea and creatinine levels and the histopathological changes in the kidney , as well as the expression of tnf- , il-6 , and mpo in the renal parenchyma .", "further research is necessary to determine the possible role of eugenol in the management of acute pancreatitis ." ] ]

[ [ "the aim of this study was to measure the levels of bdnf in periodontal tissues from patients with chronic periodontitis .", "the presence of polymorphisms rs6265 and rs4923463 of the bdnf gene and its correlation with inflammatory and clinical parameters were also assessed .", "bdnf is reported to be involved in the joint inflammatory process and its production is increased in response to proinflammatory cytokines . although a role for bdnf in periodontal regeneration has been proposed , no information is available concerning bdnf and periodontal disease .", "setting , neurotrophin brain - derived neurotrophic factor ( bdnf ) has been reported to enhance periodontal tissue regeneration [ 4 , 5 ] .", "periodontal health can be described as a dynamic state where the activity of proinflammatory / antimicrobial cytokines to control infection is optimally balanced by anti - inflammatory mechanisms to prevent unwarranted inflammation . in subjects susceptible to periodontal disease ( pd ) , an imbalance of the inflammatory response results in excessive production of proinflammatory cytokines and the subsequent loss of periodontal attachment . on the other hand ,", "furthermore , the release of tissue regenerating factors may contribute to periodontal regeneration by regulating the function of periodontal ligament cells , endothelial cells , and cementoblasts . in this" ], [ "periodontal examination was performed in both groups of patients , cp and hc , at the initial visit to determine probing depth ( pd ) , clinical attachment loss ( cal ) , and bleeding on probing ( bop ) .", "patients in this study met the following inclusion criteria : previous history of cp , diagnosed according to previously described criteria : ( 1 ) exhibiting more than one tooth with probing depth higher than 5 mm , ( 2 ) exhibiting more than two sites with clinical attachment loss deeper than 6 mm , and ( 3 ) exhibiting lesions distributed in more than two teeth in each quadrant .", "twenty - eight patients with cp , treated at the periodontal clinic , school of dentistry , at universidade federal de minas gerais ( ufmg , brazil ) , were enrolled in this study .", "the control group ( hc ) comprised 29 age and gender matched periodontally healthy patients enrolled for third molar removal surgery .", "periodontal tissue samples from periodontal pockets or healthy oral mucosa extracted during surgery of impacted third molars were fixed in 10% buffered formalin , embedded in paraffin wax , and cut longitudinally ( 3 m ) .", "periodontal tissue samples were also used for determination of myeloperoxidase ( mpo ) activity , a neutrophil enzyme marker , as described earlier ." ], [ "the levels of bdnf and the inflammatory mediators cxcl10 and tnf- were increased in gg genotype of bdnf rs6265 polymorphism ( figures 3(a ) , 3(b ) , and 3(c ) ) , but mpo levels did not alter significantly ( figure 3(d ) ) . in bdnf", "rs4923463 polymorphism the levels of bdnf and mpo did not differ , but the levels of cxcl10 and tnf- were higher in patients with aa genotype ( figures 3(e)3(h ) ) .", "the bdnf and il-10 levels in periodontal tissues were negatively correlated ( r = 0.691 , p = 0.002 ) , whereas no correlation between bdnf and il-17a , tnf- , cxcl10 , or clinical parameters was observed ( pd , cal , and bop ) . following the clinical investigation , the frequencies of polymorphisms ( bdnf ) were assessed in blood samples of hc and cp subjects ( table 2 ) . the frequency of these genotypes agreed with the hardy - weinberg equilibrium ( p > 0.05 ) .", "the levels of il-17a , cxcl10 , il-10 , tnf- , and bdnf in periodontal tissues were greater in cp patients than in controls ( figure 1 ) .", "moreover , the mpo activity and the inflammatory infiltrate in the periodontal tissues , characterized by polymorphonuclear and mononuclear leukocytes , were significantly higher in the cp than in the hc group ( figure 2 ) .", "the clinical features pd , cal , and bop were significantly higher in the cp than in the hc group ( p < 0.0001 ) ( table 1 ) ." ], [ "the present study is the first to demonstrate that bdnf levels were increased in periodontal tissues from chronic periodontitis compared to healthy subjects . in agreement with our findings", "in conclusion , bdnf seems to be related to periodontal pathogenesis and also involved in tissue repair .", ", bdnf was found in high levels in the plasma of patients with osteoarthritis and in patients with rheumatoid arthritis .", "nevertheless , we found that subjects with gg ( rs6265 ) genotype expressed higher levels of bdnf in periodontal tissues , in agreement with a previous report showing that bdnf - m66 variant alters intracellular trafficking and impairs bdnf secretion . on the other hand , rs6265 polymorphism", "we can hypothesize that the concomitant increase of bdnf , tnf- , and cxcl10 in patients with the gg genotype may be an attempt of the host to induce periodontal healing ." ] ]

[ [ "we analyzed information about 634 immigrants from latin america seen at the tropical medicine unit of the ramn y cajal hospital in madrid , spain , during april 1989june 2008 .", "roundworm seroprevalence ( < 68% ) in patients with eosinophilia of unknown cause ( 8) .", "albendazole is the treatment of choice for vlm ; for practical purposes , it could be recommended for presumptive treatment in immigrants from latin america with eosinophilia in whom strongyloidiasis is suspected ( 13 ) ." ], [ "albendazole is an effective and relatively safe drug that could be used to treat suspected vlm and other concomitant nematode infections , including cryptic s. stercoralis threadworm infections .", "vlm may be difficult to diagnose , especially in immigrants from regions in latin america where polyparasitism is endemic .", "empirically described treatment may lead to resolution of clinical symptoms , even though ivermectin is a better treatment for chronic strongyloidiasis .", "positive serologic test results , marked eosinophilia , absence of other helminthic infections , compatible clinical signs , and disappearance of symptoms after specific treatment can help establish a vlm diagnosis , especially in areas of low parasitism .", "vlm should be included in the differential diagnosis of eosinophilia in immigrants ( children and adults ) from tropical areas if respiratory or abdominal symptoms are evident ." ] ]

[ [ "the aim of this study was to investigate possible factors associated with pain intensity among turkish school children with nlbp , aged 1018 years , and to determine the relationship between related factors and pain intensity using the regression tree method .", "although lbp has generally been believed to be uncommon before the age of 20 , the prevalence of lbp among school children and adolescents has been reported to be high in different parts of the world , mostly in western countries , where it varies from 1040% .", "many studies have analyzed the risk factors associated with lbp in children and adolescents to describe risk factors profiles [ 3,58 ] . to our knowledge", "lbp has a significant economic impact on individuals , society , and quality of life .", "there have been no reports on nlbp and related factors among school children in turkey .", "the nhanes ii ( national health and nutrition examination survey series ) reported the onset of lbp before the age of 20 in 11% of the general population .", "these studies show that the prevalence of lbp in children is high , equaling that of adults by the end of the growth period ." ], [ "the dependent variable was pain intensity measured in cm , and the independent variables were bmi , sex , regular exercise habit , studying posture , transportation to / from school , duration of studying , bag handling and type of bed ", "this study was conducted on school children aged 1018 years in the city of denizli , located in the western part of turkey . out of 88 primary and high schools in the city ,", "the regression tree method ( rtm ) was used to determine risk factors that may affect pain intensity .", "the association between risk factors ( x ) and outcome variable ( y ) ( pain intensity , in this study ) are examined by a schematic representation .", "the participants were asked to select 1 of the following studying postures : ( 1 ) sitting on chair and studying on a table , ( 2 ) sitting on ground without chair and table , and ( 3 ) lying in prone or supine position on a bed .", "the visual analog scale ( vas ) was used for measuring the intensity of pain .", "the vas is designed to present to the respondent a rating scale with minimum constraints ." ], [ "two methods of enquiry about nlbp were used , namely a direct question and a pre - shaded manikin question : have you ever had low back pain ? ( look at the drawing ) have you experienced pain in the shaded area which lasted for 1 week , a month , or longer ? students who answered both of the questions as " ], [ "homogeneous groups are constituted according to the adequate cut - off values of the risk factors . at the beginning , all individuals are collected in 1 group called a root node .", "splitting continues until the tree reaches maximum size , and then passing the selection of adequate tree structure stage , called pruning .", "homogeneous groups that come into being based on recursive binary splitting are termed terminal node . the homogeneous group means that this group is sufficiently homogeneous and can not be split any more .", "the association between risk factors ( x ) and outcome variable ( y ) ( pain intensity , in this study ) are examined by a schematic representation .", "the maximum tree is not used for every data set because of its overfit structure . after pruning ,", "the values that take place in the terminal nodes give the mean and variance of that group .", "there is no assumption about distribution shapes of risk factors , but outcome variable should be numeric . in rtm", "the regression tree method ( rtm ) was used to determine risk factors that may affect pain intensity ." ], [ "the overall mean and standard deviation of pain intensity was 2.580.86 ( minimum=1 , maximum=5 ) . among the risk factors used in this study , duration of studying , type of bed , transportation to / from school , and bmi score were found to have a significant effect on pain intensity , while sex , studying posture , regular exercise habit , and bag handling were not significant ( figure 1 ) . as will be seen from figure 1 ,", "these are as follows : group ( id=124 ) : studies less than 4 hours , uses school bus for transportation and has 17.13 < bmi < 20.9 ( mean pain score=1.74 ) .", "the descriptive statistics are shown ( table 1 ) as mean sd and as frequencies and percentages .", "this group is the highest risk group among the 6 groups , giving the highest mean .", "6 homogeneous groups are defined by the rtm according to pain intensity , with an increasing order .", "this group is the lowest risk group among all 6 groups , giving the lowest mean ." ], [ "this shows that quality of sleep is a very important factor affecting pain intensity for subjects who suffer from low back pain .", "we also found that the sex of the children was not an important factor in nlbp intensity .", "lee and chiou found that poor sitting habit were statistically associated with lbp . in our study , studying posture was not found to be an important factor .", "we found also a significant relationship between the type of bed and low back pain intensity .", "duration of studying : we also found a significant relationship between duration of studying and nlbp intensity .", "korovessis et al . in 2004 reported that dorsal pain increased with increasing backpack weight among children ." ], [ "therefore , health care providers should evaluate school children carefully and make accurate observations in terms of risk factors , including duration of studying , type of bed , transportation to / from school , and obesity , to predict any severe musculoskeletal problems , especially nlbp . finally , physical factors and musculoskeletal risk factors are especially important in terms of nlbp in school children .", "results from the literature , as well as our study , show that taking parents and teachers concerns seriously is of vital importance .", "further studies are needed to investigate psychosocial risk factors and their relationships with nlbp in school children ." ] ]

[ [ "this study was developed and approved by the steering committee of the translating research into action for diabetes ( triad ) study and conducted in one of triad 's six translational research centers , kpnc .", "approximately 550 women had no diagnosis of gdm but met the nddg criteria ( equivalent to 4% of the size of our gdm cohort with a diagnosis ) ; women without a diagnosis of gdm were excluded from the analysis . for the first and second aims , the primary outcome was performance of postpartum screening for diabetes by either an fpg test alone or a 75-g , 2-h ogtt . because several weeks may elapse before glucose metabolism returns to normal in most women with gdm ( 15 ) , the american diabetes association ( 16 ) and the american college of obstetricians and gynecologists ( 17 ) both recommend that postpartum glucose screening be performed at 6 weeks postpartum or later .", "therefore , when we report on trends in postpartum conversion to diabetes , we report only on the fasting values detected by either an fpg or an ogtt . for the fourth aim", "we included only women who met the nddg criteria of gdm because , in this clinical setting , the nddg criteria were used for diagnosis of gdm until january 2007 .", "the direct method was used to calculate the yearly age- and race / ethnicity - adjusted rates of ifg and diabetes diagnosed by fpg ." ], [ "the yearly age- and race / ethnicity - adjusted proportion of women with gdm who had postpartum glucose screening and 95% cis were calculated by the direct method , in which the age and race / ethnicity distribution of the entire study population was used as the standard . among women who had postpartum screening ,", "the direct method was used to calculate the yearly age- and race / ethnicity - adjusted rates of ifg and diabetes diagnosed by fpg .", "predictors of postpartum screening were examined in a multivariable logistic regression model adjusted for age , race / ethnicity , education , income , obesity , parity , gestational age at gdm diagnosis , glyburide and insulin use during pregnancy , a macrosomic infant at the index pregnancy , visits to an internal medicine or obstetrics / gynecology provider during the postpartum period , year of delivery , and medical facilities .", "this study was approved by the human subjects committee of the kaiser foundation research institute ." ], [ "we identified 14,448 pregnancies complicated by gdm occurring between 1995 and 2006 among kpnc members who were aged 1544 years and delivered live infants or had still births .", "the percentage of women with gdm pregnancies who received a postpartum glucose screening test increased from 1995 ( 20.3% ) to 2006 ( 55.9% ) . between 1995 and 2006 ,", "the proportion of women with ifg postpartum remained similar over time , but the proportion of women with diabetes decreased from 19951997 to 19982000 and then leveled off ( fig ." ], [ "we identified 14,448 pregnancies complicated by gdm occurring between 1995 and 2006 among kpnc members who were aged 1544 years and delivered live infants or had still births .", "the percentage of women with gdm pregnancies who received a postpartum glucose screening test increased from 1995 ( 20.3% ) to 2006 ( 55.9% ) . between 1995 and 2006 ,", "these pregnancies occurred among 13,547 women , because 901 had more than one pregnancy during the 12-year study period .", "the age of women with gdm increased slightly ( 28.2 5.7 to 28.8 6.0 years ) and the proportion of women with gdm who were hispanic increased markedly .", "changes in the demographics represent changes in the entire population with gdm , regardless of performance of diagnostic screening . after adjustment for age and race / ethnicity , the proportion of women with gdm who received a postpartum glucose screening increased steadily over time from 20.7% ( 95% ci 17.823.5 ) in women who delivered in 1995 to 53.8 ( 51.356.3 ) in women who delivered in 2006 ( fig ." ], [ "unadjusted characteristics of women by postpartum screening status are illustrated in table 1 . in a multiple - adjusted logistic regression model ( table 2 ) , older age , asian or hispanic race / ethnicity , higher education , at least two prior births , earlier gestational age at gdm diagnosis , use of insulin or glyburide during pregnancy , and visits to an internal medicine or", "obstetrics / gynecology provider during the postpartum period were independent and significant predictors of postpartum screening ." ], [ "on the basis of fpg ( either performed alone or as part of the ogtt ) , 3.5% ( n = 191 ) had diabetes and 22.0% ( n = 1,228 ) had ifg .", "the proportion of women with ifg postpartum remained similar over time , but the proportion of women with diabetes decreased from 19951997 to 19982000 and then leveled off ( fig .", "564 were screened at postpartum , and 131 had ifg and 32 had diabetes by fpg ( age- and race / ethnicity - adjusted rates 24.2 [ 95% ci 20.27.8 ] and 6.1 [ 4.28.1 ] , respectively ) . among women who delivered in 20042006 , 2,381 women were screened , and 583 had ifg and 80 had diabetes by fpg ( age- and race / ethnicity - adjusted rates 24.3 [ 22.626.0 ] and 3.3 [ 2.64.0 ] , respectively ) ." ], [ "the proportion of women receiving an ogtt increased from 1995 ( 5.0% ) to 2005 ( 16.6% ) and markedly increased in 2006 ( 71.5% ) . in 2006 , kpnc instituted a nurse managed care program that included greater attention to postpartum screening guidelines . among the 600 women who underwent a 75-g ogtt in 2006 , 16 had diabetes at postpartum .", "of the 188 women who were found to have pre - diabetes ( i.e. , either ifg or igt according to the fasting or 2-h glucose values measured during the 75-g ogtt ) , only 114 ( 60% ) were diagnosed with ifg ; 74 ( 40% ) would have been classified as having normal glucose tolerance on the basis of fpg alone .", "diabetes was diagnosed in 4 ( 25% ) by fpg alone . of the remaining 12 women , 8 ( 50% ) had ifg and 4 ( 25% ) had normal fpg .", "therefore , 78 ( 38% ) of the 204 women with either diabetes or pre - diabetes were identified only by the 2-h glucose measurements ." ], [ "in a managed care plan with a large number of women with gdm pregnancies , we found that between 1995 and 2006 , screening for postpartum diabetes increased from 20.7 to 53.8% .", "a diagnosis of pre - diabetes would identify women at high risk of future maternal diabetes , but this risk could be reduced through the application of interventions such as thiazolidinediones , metformin , or intensive lifestyle modification ( 3,4 ) . we conclude that , among women with a gdm history , postpartum diabetes screening has increased , but screening is still suboptimal .", "the increase in screening performance is not likely to be due to advancing maternal age or changes in the racial / ethnic composition of women with gdm , as this trend in screening performance was similar after adjustment for age and race / ethnicity , and almost the entire population of pregnant women was screened for gdm between 1995 and 2006 . although the proportion of women with ifg on their postpartum screen did not significantly change over time , the proportion of women with diabetes ( diagnosed by fpg levels ) at postpartum decreased by 50% .", "this observed decrease in diabetes among women with postpartum screening is not likely to be a consequence of the small increase ( 3% ) in gdm screening over time .", "postpartum screening and subsequent diagnoses of diabetes affect not only the mothers but also future pregnancies" ] ]

[ [ ", we describe the role of ectophosphatase activities in host - parasite interactions , particularly ectophosphatases in parasitic protozoa and fungi .", "these strategies have brought new perspectives of researches in the areas of biochemistry , physiology , and genetics , providing knowledge about the microorganisms ' life cycles , as well as predicting diagnostic biomarkers , novel drug targets and vaccine candidates against parasitic infections . ", "the balance between the antagonistic activities of protein kinases and phosphatases are responsible for many cellular functions , including metabolic pathways , cell - cell communication , proliferation , and gene transcription . ", "/ threonine / tyrosine residues at the cell surface make this set of enzymes a key tool for the survival of pathogens in hostile environments and escaping the host immune responses [ 19 , 2224 ] . in this review" ], [ "little is still known about the physiological role of protein phosphatase activity in trypanosomatids , even though the first demonstration of this activity in trypanosoma brucei and t. cruzi took place in 1972 .", "t. brucei is an exclusively extracellular parasite that resides in the bloodstream of the mammalian host .", "along with those , cell surface components play a key role in the survival of protozoan parasites in hostile environments and in confrontation with host immune responses . since , these flagellates have an unusual composition of phosphatases with the ptp family being greatly reduced while the stp family is expanded by comparison with human phosphatases .", "t. cruzi invades and replicates in many cell - types , including macrophages , fibroblasts and myocytes ." ], [ "the fungal cell wall is a compact albeit dynamic structure that plays important roles in several biological processes determining cell shape , morphogenesis , reproduction , cell - cell and cell - matrix interactions , osmotic and physical protection .", "it is reasonable the hypothesis that ectophosphatases represent a virulence marker , since these enzymes represent part of the outer layer and are linked to cell differentiation and host cell - pathogen interactions .", "several different cell wall components have been characterized such as specific enzymatic activities , heat - shock proteins , glycosphingolipids ( gsl ) , melanin , histone and integrin - like proteins .", "intriguingly , known activators of signaling pathways and cell differentiation , paf and propanolol , promoted an enhancement of f. pedrosoi ectophosphatase activity suggesting that f. pedrosoi ectophosphatase may be considered a surface marker for morphological transition and infection . in the fungus c. neoformans a thick capsule composed of neutral and charged polysaccharides , can be modulated by different environmental conditions , including the sites of fungal infection inside the host ." ], [ "the balance of phosphorylation - dephosphorylation of serine , threonine and tyrosine residues modulates signaling pathways critical for determining the outcome of multiple cellular functions .", "further studies are warranted to resolve the roles of ectophosphatases in host - pathogen interactions , as well as the possible correlations between the expression of these enzymes and the clinical manifestation of the diseases ." ] ]

[ [ "an association between alexithymia and dissatisfaction with life has been found in some studies of coronary heart disease patients .", "during the recent decade , a number of researchers have described the growing psychosocial risk factors for coronary heart disease ( chd ) , which include depression , anxiety , stress , and alexithymia that decrease the health - related quality of life and protective factors such as social support .", "alexithymia has been shown to be associated with several medical conditions and mental health problems .", "some researchers believe that dysfunction in the limbic system , brain abnormal lateralization , and/or difficulty in the efficiency of hemispheric communication are the causes of its emergence . the prevalence of alexithymia in working age populations has been shown to be about 9 - 17% for men and 5 - 10% for women . at the population level , alexithymia is associated with older age , lower socioeconomic status , fewer years of education , single marital status , and poorer perceived health ." ], [ "this research was a cross - sectional study that examined the causal relationship between alexithymia and dass ( depression , anxiety , stress ) , quality of life , and social support .", "the sample consisted of 398 chd patients ( 166 females and 232 males and age : 40 - 70 years ) , who were randomly selected from the isfahan chamran heart center and isfahan cardiovascular research center ( icrc ) ( 2013 ) and the other heart clinical center .", "this questionnaire was standardized on a sample of 2,956 healthy and 2,936 unhealthy rural and urban inhabitants ( age 30 years and above ) from isfahan , najaf - abad , and arak , who participated in the isfahan healthy heart program ( ihhp ) from two dissimilar iranian provinces , during 2006 .", "the internal consistency reported in a clinical sample from iran , using cronbach 's alpha for the total tas-20 scale and subscales of dif , ddf , and eot , were .", "66 , respectively , and the total validity using test retesting for tas-20 and its subscales dif , ddf , and eot were .", "the patients filled in five questionnaires assessing depression , anxiety , stress ( dass-21 ) , alexithymia ( tas-20 ) , health - related to quality of life ( whoqol-26 ) , multiple scale of perceived social support ( mspss-12 ) , and another questionnaire , which obtained demographic information . before attending the study , each patient had been examined by a cardiologist , who had confirmed the diagnosis as coronary heart disease ." ], [ "patients descriptive characteristics cronbach 's alpha was calculated as 0.74 for the toronto alexithymia scale ( tas ) , 0.89 for the depression , anxiety , and stress scale ( dass ) , 0.87 for the multidimensional scale of perceived social support ( mspss ) , and 0.90 for the world health organization quality of life questionnaire ( whoqol ) . based on the conceptual model", "comparative and parsimonious fit indices according to all the mentioned indicators , the default model presented a good fit for the relationship between alexithymia and depression , anxiety , stress , quality of life , and social support .", "[ figure 1 ] of the study , the structural model of variables ( i.e. , tas , dass , mspss , and whoqol scores ) was presented using the outputs of amos .", "therefore , three main groups of indices ( absolute fit , comparative fit , and parsimonious fit indices ) are used to fit a model ." ], [ "based on the conceptual model [ figure 1 ] of the study , the structural model of variables ( i.e. , tas , dass , mspss , and whoqol scores ) was presented using the outputs of amos .", "the conceptual model of alexithymia according to table 3 [ relative chi - square ( cmin / df ) = 2.580 and df = 58 for default model ] , the model fitted well . even as most experts consider relative chi - square values of 2 - 3 to show a good fitting model , schumacher and lomax expanded the range to 1 - 5 .", "comparative and parsimonious fit indices according to all the mentioned indicators , the default model presented a good fit for the relationship between alexithymia and depression , anxiety , stress , quality of life , and social support .", "therefore , three main groups of indices ( absolute fit , comparative fit , and parsimonious fit indices ) are used to fit a model .", "although in traditional statistical methods , the researcher uses a single measure to verify the null hypothesis , the complexity of the structural equation modeling eliminates this single measure .", "as rmsea < 0.08 is acceptable , our default model fitted well ( rmsea = 0.06 ) . in addition , the holter index of 204 was again indicative of a well - fitting model ." ], [ "the present study has examined the predictive value of alexithymia in changes in depression , anxiety , stress , social support , and quality of life among patients with coronary heart disease . after fitting all the data", "this research showed the relation between alexithymia and ( depression , anxiety , stress ) , social support , and quality of life , as a psychological structural model in chd .", "the limitations of the study were : inability to control the behaviors that were associated with alexithymia and could thus affect the relationship between alexithymia and depression , anxiety , stress , social support , and quality of life", "according to the results of the present study it is important to pay attention to alexithymia as an important variable associated with ( depression , anxiety , stress ) , social support , and quality of life of patients with coronary heart disease .", "it can be concluded that alexithymia is connected with the pathological indicators of cardiac disease ( depression , anxiety , and stress ) and its protective parameters ( social support and quality of life ) ." ], [ "the results highlight the importance of alexithymia as a risk factor associated with neuroticism ( anxiety , depression , and stress ) and social support which reduces the quality of life among coronary heart disease patients . in this", "conducting longitudinal studies in this area may lead to more interesting and favorable results , which is recommended to the researchers interested in this field .", "regard , psychological interventions are recommended to reduce the consequences of this disorder , especially among coronary heart disease patients .", "the present study showed the structural relations between the psychological factors associated with alexithymia in coronary heart disease ." ] ]

[ [ "tumor - induced osteomalacia ( tio ) is a rare paraneoplastic disease in which causative tumor ( generally of mesenchymal origin ) gives rise to an oncogenic osteomalacial syndrome , whose underlying pathogenetic mechanism is related to the tumor s production of a phosphaturic factor that reduces the renal reabsorption of phosphates and causes renal phosphate leak . the tumors are generally small , slowly growing and non - invasive .", "most are localized at long bone level , but they are frequently impossible to locate and the correct diagnosis may take 5 - 7 years .", "the consequent rehabilitation treatment must consider the complexity of the clinical - functional picture of the patient , especially if a substitution megaprothesis surgery is needed .", "the clinical picture is characterized by non - specific symptoms , such as hyposthenia , worsening myalgia and bone pain ( mainly affecting load - bearing areas ) , and gait alterations ( anserine gait ) . until a correct diagnosis has been made patients usually undergo symptomatic treatments without success .", "the elective surgical treatment of tio is tumor resection , which normally leads to a complete regression of the osteomalacial syndrome .", "those patients history is characterized by numerous pathological fractures , periprothesical fractures and prothesis mobilizations ." ], [ "the clinical picture is characterized by non - specific symptoms , such as hyposthenia , worsening myalgia and bone pain ( mainly affecting load - bearing areas ) , and gait alterations ( anserine gait ) . until a correct diagnosis has been made patients usually undergo symptomatic treatments without success .", "the consequent rehabilitation treatment must consider the complexity of the clinical - functional picture of the patient , especially if a substitution megaprothesis surgery is needed .", "the elective surgical treatment of tio is tumor resection , which normally leads to a complete regression of the osteomalacial syndrome .", "those patients history is characterized by numerous pathological fractures , periprothesical fractures and prothesis mobilizations ." ], [ "because of the persistence of the painful symptoms , a bone biopsy of the humeral lesion was performed ; that led to the diagnosis of a spindle cell mesenchymal tumor , morphologically arising from a glomus tumor . given the suspicion of tio , the patient underwent octreotide scintigraphy , which revealed increased tracer uptake at the level of the medio - proximal third of the right humerus . in january 2005 , she underwent a first surgical intervention that involved curettage of the lesion , an autograft from the ipsilateral tibia , and a bone biopsy , thus allowing the final diagnosis of a phosphaturic mesenchymal tumor . as a result of an accidental fall in july 2005 , the patient suffered a subcapital fracture of the right femur and a bifocal fracture of the previously treated right humeral diaphysis .", "the clinical history of pm ( born in 1945 ) began in 2000 , when she consulted her general practitioner because of widespread costal and vertebral pain of no known traumatic cause , mainly localized in the dorso - lumbar region ." ], [ "those lesions can lead to pathologic fractures , which , if treated without removing the neoformation or with a partial excision , may recur subsequently , along with loosening or displacement of prothesis components .", "for this reason , the worsening pain and progressive loss of functional capacities can reduce the compliance with treatment and affect patient mood .", "the tumor - induced osteomalacia is a paraneoplastic syndrome , which causes osteomalacy , causing small dimension lesions , characterized by a slow growth without any specific anatomic localization .", "the lesions can be studied with x - rays , computed tomography , magnetic resonance imaging , concreotide tri - phasic whole - body scintigraphy and f-18 fluorodeoxyglucose positron - emission tomography .", "having confirmed the nature of the lesion , treatment of a phosphaturic - secreting mesenchymal tumor is its surgical removal with broad margins by means of unconventional techniques such as a large resection and prosthetic implantation . in absence of a correct diagnosis ,", "the rehabilitation treatment of patients with tio was initially based on reducing / containing the painful symptoms and asthenia , and is naturally not beneficial ." ], [ "the protocol developed at the gaetano pini orthopedic institute with the collaboration of the rehabilitation and orthopedic team has demonstrated to be effective in the case above described .", "the functional pictures which result are often complex for the long diagnostic - therapeutic pathway and for the highly invasive surgery needed .", "the scientific research has not validated any standard rehabilitation protocol or any specific guidelines yet ." ] ]

[ [ "therefore , the objectives of this community - based study were to investigate the prevalence of porcine cysticercosis and associated risk factors in pigs within study area . moreover , findings of this study will assist to develop the control strategies of porcine cysticercosis for the public health aspect .", "human neurocysticercosis ( ncc ) is caused by larval stage of zoonotic tapeworm taenia solium ( pork tapeworm ) which remains a major public health problem in developing and some developed countries .", "porcine cysticercosis is the cause of human taeniasis and neurocysticercosis is a consequence of taeniasis .", "due to lacking of information on porcine cysticercosis in myanmar up to now , it is important to investigate the prevalence and associated risk factors .", "one of the main obstacles to control the t. solium infections is the lack of adequate epidemiological data on cysticercosis / taeniasis ." ], [ "the cross - sectional studies were conducted from january to march and june to july 2014 , to investigate the prevalence of taenia solium cysticercosis in slaughtered and farmed pigs within pyinmana , lewe , and tatkon townships , nay pyi taw area .", "the questionnaire interviewed data were analyzed for the relationship between the prevalence of t. solium cysticercosis and hypothesized risk variables such as age , gender of pigs , husbandry system , feed type , environment of pig farm ( accessibility of human feces ) , personal hygiene of owners , pork consumption , cooking and eating habit of pork , use of anthelmintics in pigs and owners , and knowledge on taeniasis .", "blood collected from the jugular vein of farmed pig was conducted for the seroprevalence and a structured questionnaire with both closed and open - ended questions was administered to owners to obtain management practices in pig husbandry .", "an expected prevalence of 30% with a confidence level of 95% was used in this unit . in this study , 300 slaughtered pigs and 364 farmed pigs from the study area were examined although calculated samples were 298 and 323 , respectively ( table 1 ) .", "a questionnaire was developed and used to collect information on hypothesized risk factors and other related pieces of information from sampled pig owners .", "it is a technique for developing a research sample where existing study subjects recruit future subjects from their acquaintances ." ], [ "univariate analysis of hypothesized risk factors of gender ( or = 3.0 ; 95% ci = 1.75.4 ) , increased age ( or = 2.3 ; 95% ci = 1.24.2 ) , husbandry system ( or = 5.1 ; 95% ci = 2.411.2 ) , feed type ( or = 16.9 ; 95% ci = 2.3124.3 ) , no hand washing habit before feeding ( or = 31.5 ; 95% ci = 4.3230.9 ) , not using anthelmintic in pigs ( or = 11.9 ; 95% ci = 5.028.5 ) and owner ( or = 2.5 ; 95% ci = 1.44.4 ) , and pork consumption of owner ( or = 37.4 ;", "seroprevalence of porcine cysticercosis in farmed pigs was 15.93% ( 58/364 ) in the study area .", "prevalence of households with pigs infected with t. solium cysticerci by ab - elisa examination was 23.15% ( 47/203 households ) .", "95% ci = 9.0156.1 ) was significantly associated with cysticercus cellulosae infection ( p < 0.05 ) .", "the prevalence in slaughterhouses of pyinmana , lewe , and tatkon townships was 22% ( 44/200 ) , 23.33% ( 7/30 ) , and 28.57% ( 20/70 ) , respectively .", "the distribution and odds ratio of significant risk factors concerning porcine cysticercosis are shown in table 2 .", "all the infected pigs presented parasites located in the tongue . only in one pig ," ], [ "the present study is the first report of t. solium cysticercosis in pigs in myanmar .", "pigs in the study area positive for cysticercosis have been exposed to t. solium eggs . among the 17 hypothesized risk factors ,", "the gender of pigs ( being female ) was significantly associated with porcine cysticercosis in this study .", "most farms are having the habit of feeding waste materials such as swill and kitchen leftover , broken rice , rice bran , groundnut meal , sesame meal and local forage , and poor sanitation .", "this prevalence with relatively high percentage of porcine cysticercosis ( 15.93% ) in ab - elisa and 23.67% in slaughtered pigs indicates the presence of human taeniasis and it also leads to the associated risk of human cysticercosis and neurocysticercosis .", "all farmers did not have the knowledge on taeniasis and cysticercosis and they have never seen the cysts in the pork in the study area . the presence of zoonotic agent , cysticercus cellulosae , may depend on intrinsic factors : age , gender , and extrinsic factors : pig husbandry system , hand - washing habit of owner , use of kitchen waste as pig feed , not using anthelmintic in pigs and owners , and pork consumption of owner in the study area" ] ]

[ [ "the conference was divided in two sections : a gathering of experiences , of paths where science meets metaphysics to have a new language born , made of images and movement , and a panel to understand how taiji quan , the arts of movement and meditation , can prolifically meet cognitive sciences and neurosciences .", "modern science , which paved the way for an outlook of reality considering the universe as a whole , in which all parts and phenomena are connected among them , can be integrated to the ancient eastern wisdom for the control of the mind and to the body arts ( taiji quan , qi gong , yoga ) to develop a new ecological awareness , an awareness based on nature and on the dynamic relation among all living creatures .", "organized by nei dan school , european school of taiji quan and by the tao and science studies centre , under the aegis of the provincia di bologna and the partnership of asi ( alleanza sportiva italiana ) and luni editrice .", "science , philosophy , medicine and body arts of the ancient east are reunited together to create a new ecological awareness of body and mind .", "speakers during the tao and science conference were : andrea pezzi ( presenter and tv author ) ; professor edwin l. cooper professor , laboratory of comparative neuroimmunology , department of neurobiology , david geffen school of medicine , university of california los angeles , editor - in - chief , the journal : evidence based complementary and alternative medicine , oxford university press ; professor carlo ventura ( professor of molecular biology at the faculty of medicine , university of bologna ; director of the laboratory of molecular biology and stem cell bioengineering , national institute of biostructures and biosystems by the institute of cardiology of santorsola malpighi hospital in bologna ) ; professor angelo marzollo ( professor of systems theory , faculty of sciences , university of udine ; vice general secretary of the international centre for mechanical sciences ; unesco ex - person in charge for mathematics and now consultant ) ; professor giovanni sambin ( professor of logic mathematics , university of padova ) ; dottor matteo luteriani ( publisher , journalist and master of martial arts ) , dottor massimo mori ( doctor , poet and master of taiji quan ) and eng .", "flavio daniele ( writer and master of taiji quan ) the following guests took part in the conference through their representatives : professor james k. gimzewski ( department of chemistry and biochemistry , university of los angeles ", "goodwill of the conference is to act as a starting point to develop a net of experts , doctors and scientists , who will investigate the dynamic interactions between spiritual insight and scientific analysis to come to the creation of a new paradigm of modern science ." ], [ "cognition , the process of knowledge , and it is identical to the process of life self . nevertheless , beyond the dialectics coming from the differences , it is more and more important to reintroduce a principle , acting as basis for the man universally , a principle which is internal and unconventional , an equal able to give the equal to all psycho - biological behaviors of the human being . in italy", "master flavio daniele emphasized as most advanced research of the last decades of the past century in the field of cognitive sciences and neurosciences led to a new theory , revolutionizing the traditional cartesian concept of mind .", "carlo ventura , md , phd : western science has long been entangled with increasing reductionism and the development of field restricted approaches to understand cell biology and the molecular basis of disease .", "disease has always been of enormous concern in human society . from prayers and spells to the birth of medicine as a rational science , man has developed all sorts of medical treatments to combat different illnesses and chronic ailments : according to the chinese proverb : life is worth more than a thousand gold pieces. the first objective in a serious approach to complementary and alternative medicine ( cam ) should be to obtain a broad understanding , with a minimum of detail , of how cam fits into the pattern of biology of the way in which the nervous , endocrine and immune systems coevolved , their function and coordination with other body systems , and their development from the embryo onwards including aging . at the same time , such an outline should provide an adequate background for easy application of cam ideas to the detail of practical cam work in public health , clinical and medical practice , and yet not stray far away from its essence , the very biology that under girds it .", "galilei was the first to propose that the laws of nature are written in the language of mathematics ." ] ]

[ [ "different electrocardiographic abnormality may be seen in dialysis patients , such as st , t change , ventricular and supra - ventricular arrhythmia and qt interval prolongation . in the electrocardiogram ,", "although there are some studies about qtc and qtc dispersion in hemodialysis ( hd ) patients with different results ; however , there are only a few studies concerning relationship of qtc internal and qtd with echocardiography findings , so the aim of this study was the evaluation of these relationship in dialysis patients .", "different cardiovascular disorders , such as left ventricular hypertrophy ( lvh ) , coronary artery diseases , congestive heart failure ( chf ) , and arterial hypertension are commonly seen in these patients .", "some predisposing factors of cardiac disorders in dialysis patients are secondary hyperparathyroidism , long term hypertension , and anemia .", "moreover , qt interval may be a predictor of ventricular arrhythmia and cardiovascular mortality in chronic kidney disease and dialysis patients ." ], [ "in a cross - sectional study , 60 hd patients with age > 18 years and the dialysis duration > 3 months were enrolled .", "the patients were on hd , by fresenius digital machine ( 4008b , germany ) and gambro digital machine ( ak95 and ak96 , sweden ) , 2 - 3 times / week , as a regular method ( 4 - 4.5 h with blood flow of 250 - 350 ml / min , dialysate flow of 500 ml / min and ultra - filtration based on the patient 's condition ) .", "also , qtd was measured by mentioned formula ( qtd = qtmax qtmin ) in 12 leads ecg .", "the used buffer was bicarbonate powder , and the type of filters were intermediate and high efficient polysulfone membrane ( r5 , r6 ) made by soha factory under license of fresenius company .", "exclusion criteria were : antiarrhythmic drugs consumption , history of cardiac diseases such as arrhythmia , heart block or chf . before dialysis session , electrocardiography ( ecg ) and echocardiography", "all data and information were confidential , and for ecg and echocardiography taking an informed consent was taken from each patient . in echocardiography , left ventricular ejection fraction ( lvef ) , lvh , pulmonary artery pressure ( pap ) and valvular disorders were evaluated .", "echocardiography and ecg were done before the dialysis session and by single cardiologist and technician respectively ." ], [ "severity of valvular disorders in the patients mr = mitral regurgitation , tr = tricuspid regurgitation , ai = aortic insufficiency echocardiographic findings and their association with qtc and qtd qtc = corrected qt , qtd = qt dispersion , pap = pulmonary artery pressure , lvef = left ventricular ejection fraction , lvh = left ventricular hypertrophy , mr = mitral regurgitation , tr = tricuspid regurgitation , ai = aortic insufficiency , pe = pericardial effusion", "in addition , no significant relation was found between qtc interval and qtd with mr , tr , ai , lvh , septal thickness ( st ) and pap [ table 3 ] . qtc interval and qtd has also no correlation with serum pth or ca , k or hco3 .", "mean urea reduction ratio in men and women were 68.14% 9.34% and 68.22% 3.88% ; however , kt / v was 1.45 0.17 and 1.49 0.16 among men and women , respectively . characteristics of patients and their association with qtc and qtd sd = standard deviation , bmi = body mass index , pth = parathyroid hormone , qtc = corrected qt , qtd = qt dispersion there was no statistically significant relationship between qtc interval or qtd with duration of dialysis , bmi , age , and gender ( p > 0.05 ) .", "qtd in all of the patients was 64.17 25.93 ms , however in men and women were 62.70 28.05 ms and 66.52 22.48 ms respectively ( p = 0.87 ) .", "mitral regurgitation ( mr ) , tricuspid regurgitation ( tr ) , and aortic insufficiency ( ai ) were found in 54 , 47 , and 11 patients respectively [ table 2 ] .", "mean body mass indexes ( bmis ) ( post dialysis ) and duration of dialysis were 21.77 3.6" ], [ "furthermore , there was no relationship between qtc interval and qtd with serum ca , k , hco3 , pth . in hd patients , cardiac abnormalities such as vascular calcification", "our findings revealed that , in hd patients , qtc interval and qtd had not any correlation with valvular disorders ( mr , ai , and tr ) , lvh or other echocardiographic findings such as pap and st .", "we could not find any study on the correlation of qtc interval with lvh or valvular heart disease in hd patients ; however , there are some studies related to the correlation of qtc and lvh with other diseases or conditions .", "similar to our study , the changes in serum ca or k of the patients during dialysis were not associated with the qtc interval in this study . moreover , in hekmat et al.s study on 49 hd patients , qtc interval had not correlation with serum electrolytes and blood gas findings . in voiculescu", ", use of a low - calcium dialysate may predispose hd patients to ventricular arrhythmias ." ], [ "by our knowledge , this is one of the first studies on the correlation of qtc or qtd with valvular abnormality and lvh in hd patients .", "there were a few studies about the relationship of qtc and lvh in nonrenal patients , so we could not compare our results with other studies .", "based on our results , in hd patients , qtc interval or qtd was not correlated with echocardiographic findings or laboratory exam results .", "therefore , it can be concluded that qtc interval prolongation probably has not any correlation with cardiac mortality of the hd patients ." ] ]

[ [ " and significantly overestimate ( or less commonly , underestimate ) the remaining amount of active asthma rescue medication in mdis without dose counters , that the techniques used to guesstimate whether a recue mdi is effectively empty are unreliable , and how having a rescue mdi with an integrated dose counter mechanism can improve the health and quality of life of patients with asthma .", "asthma is a chronic inflammatory condition of the airways , characterized by limited airflow and punctuated by acute symptoms related to hyperresponsiveness to a variety of triggers , such as allergens or fumes ( 1 ) .", "accurately assessing the doses in an mdi is critically important for bronchodilating medications used for rescue from acute asthma symptoms .", "most asthma medications are delivered as orally inhaled products in order to achieve local effects in the lung and to minimize systemic adverse effects . inhaled asthma medications are categorized into two general classes : long - term control medications ( also known as preventive or maintenance medications ) , which are taken regularly to achieve and maintain control of persistent asthma , and rapid - acting drugs ( also known as rescue medications ) taken as needed to provide prompt reversal of acute airflow limitation and relieve bronchospasm .", "if lifestyle changes do not successfully prevent and control asthma symptoms , pharmacologic therapy can reduce the frequency and severity of asthma exacerbations , and reverse airflow obstruction during acute attacks ( 2 ) ." ], [ "we searched embase and medline english literature up to july , 2012 with search terms dose counter and asthma and dose counter and metered dose inhaler . when pertinent articles were identified , we searched for relevant references used in those papers . for environmental reasons , inhalers with chlorofluorocarbon ( cfc ) propellant", "were no longer sold in the us from 2009 , and the propellant in current mdis is hydrofluoroalkane ( hfa ) ; however , much of the research reviewed here was conducted on mdis with cfc propellant ." ], [ "moreover , physician inspection of dose counters at office visits may provide a means of evaluating patient adherence to treatment and present an opportunity to discuss appropriate use of the mdi and proper inhalation technique .", "in addition to relieving anxiety , reliable knowledge of when to replace an mdi can improve asthma management and , in turn , improve patients quality of life ( 25 ) . because they are preferred by patients ( 22 )", "activating a nearly empty or an altogether empty mdi to deliver orally inhaled asthma medication appears to be a common occurrence when patients use an mdi without a dose counter ( 12,14,15 ) .", "is both costly and wasteful , relying on rescue medication from a depleted mdi during acute bronchospasm can be life - threatening . in the study by holt and colleagues , collected mdis labeled to contain 200 salbutamol doses", "thus , it is not surprising that patient satisfaction studies consistently show wide acceptance and approval of dose counters on mdis ( 2224 ) . patients rate dose counters among the top 5 best features of their mdi ( 14,23 ) ." ], [ "the invention of the metered - dose valve led to development of mdis in the 1950s ( 13 ) .", "the dosing and performance and , consequently , drug efficacy may be directly dependent on the design of the mdi .", "in addition to the bronchodilating drug , the formulation contains a liquefied gas propellant ( hfa ) and may contain nonactive excipients . with current valve designs , it is not possible for an mdi to cease delivering drug doses completely at an exact point .", "shown here is a proair metered - dose inhaler ( manufactured by teva pharmaceutical industries , ltd . , horsham , pa ) .", "shown here is a proair metered - dose inhaler ( manufactured by teva pharmaceutical industries , ltd .", "mdis continue to deliver a spray , which may not be within the labeled specifications for the active drug , for up to twice the nominal number of recommended doses ." ], [ "studies conducted to assess the accuracy of asthma patients ability to gauge doses remaining in their mdis have consistently shown high error rates ( 14,15,20,21 ) . as noted , the only way to reliably determine the number of remaining doses in an mdi with no dose counting feature is by carefully and consistently tracking each dose , then subtracting it from the labeled number of doses .", "it has been suggested that floating an inhaler in water , known as a float test , can provide a measure of the inhaler s useful contents ( 20 ) .", "however , no universal flotation status accurately reflects when a device has reached the maximum recommended number of actuations ( 15 ) .", "moreover , this test is not only unreliable since some inhalers will float when they are full , it may damage the mdi by obstructing the metering valve ( 1517 ) .", "estimations of whether an mdi requires replacement based on the weight of the inhaler , or on the force , sounds , and taste of the actuation , are often made based on the volume of the remaining propellants and excipients and not on the remaining doses of active medication meeting therapeutic specifications ( 15,17 ) . in a study by rubin and durotoye of pediatric asthma patients , 72% of the children ( or their parents ) reported using an mdi until they could no longer ", "however , many people are not even aware of the recommended number of drug doses in their mdis . in a study conducted to investigate how asthma sufferers determined when to replace their mdis", "other methods by which patients estimate remaining medication in their mdis are not reliable ( 1315 ) ." ], [ "holt and colleagues asked patients receiving asthma treatment to return their mdis , when deemed empty , to their physicians ( 21 ) .", "is both costly and wasteful , relying on rescue medication from a depleted mdi during acute bronchospasm can be life - threatening . in the study by holt and colleagues , collected mdis labeled to contain 200 salbutamol doses", "most of these 87 patients ( 82% ) considered their mdi empty only when nothing came out of it , making it likely that they were inhaling only propellant for many doses , thereby increasing their risk of prolonged bronchoconstriction and airflow limitation requiring urgent care .", "a bronchodilator prescription typically requires refill only a few times a year , yet almost 20% of patients reported refilling their inhaler at least once a month .", "the authors speculated that the excessive number of bronchodilator refills might be due , in part , to throwing away partially used inhalers to forestall the prospect of finding an inhaler empty during an acute asthma event ( 14 ) . \n", "in practice , patients who are not tracking rescue medication doses often either discard an mdi that may still contain acceptable metered doses of drug , or continue to use a product that may no longer contain the labeled within - specification dosage ." ], [ "when asked , many patients report that not knowing how much medication is left in their mdis makes them anxious about receiving a subtherapeutic dose or no medication at all ( 22,24 ) .", "thus , it is not surprising that patient satisfaction studies consistently show wide acceptance and approval of dose counters on mdis ( 2224 ) . patients rate dose counters among the top 5 best features of their mdi ( 14,23 ) .", "dose counters are , therefore , likely to alleviate patient anxiety about running out of asthma medication in emergency situations .", "moreover , physician inspection of dose counters at office visits may provide a means of evaluating patient adherence to treatment and present an opportunity to discuss appropriate use of the mdi and proper inhalation technique .", "in addition to relieving anxiety , reliable knowledge of when to replace an mdi can improve asthma management and , in turn , improve patients quality of life ( 25 ) . because they are preferred by patients ( 22 )" ], [ "in 2003 , the us food and drug administration issued a guidance to industry emphasizing the importance of ( but not requiring ) integrated dose counters or dose indicators on mdis for orally inhaled medications targeted to the lungs ( 16 ) .", "dose indicators that rely solely on a color coded display or indicator symbol to signal when the mdi is nearing the end of its recommended doses are less precise than dose counters that use a numeric display ( figure 2 ) . typically , discarding an mdi", "if there is a down - side to integrated dose counting mechanisms on mdis , it may be that they are more expensive to produce than mdis without them .", "the expiration date for a rescue inhaler is generally 1 year after the prescription is filled ( 26 ) or after the foil pouch is opened ( 27 ) . at present , the only available albuterol rescue inhalers with integrated dose counting mechanisms are proair hfa ( teva pharmaceutical industries , ltd . ) ( 26 ) and ventolin hfa ( glaxosmithkline ) ( 27 ) .", "after 2008 , generic albuterol inhalers stopped being made because they contained cfc propellant ( it is unknown when generic albuterol inhalers may be available again ) .", "nevertheless , dose counters may reduce health care costs by decreasing asthma - related morbidity and attendant medical costs ( 14,17 ) .", "the estimated annual expenditure related to health care and lost productivity due to asthma was more than $ 20 billion according to the national heart , lung , and blood institute ( 28 ) .", "for example , inhalation of rescue medication rather than propellant to control acute bronchospasm and quell acute asthma symptoms may avoid the cost of an emergency room visit ( 29 ) ." ], [ "although there have been relatively few studies conducted to assess the use of mdis , they consistently show patients frequently overestimate the amount of active asthma rescue medication in mdis without dose counters .", "dose counters provide the only accurate and practical method of ascertaining the remaining number of effective doses in an mdi . by ensuring that patients do not use a rescue mdi beyond the recommended number of actuations and that they are receiving the appropriate metered dose of asthma medication", ", dose counters can improve asthma management and potentially decrease asthma - related morbidity and mortality , and improve patients quality of life .", "for these reasons , integrated dose counting mechanisms should be required on mdis that deliver asthma rescue medication ." ] ]

[ [ "for all 3 mutations of eis associated with kanamycin resistance , rrs was wild type .", "* miru - vntr , mycobacterial interspersed repetitive unit variable number tandem repeat ( original 12-loci profile ) . included genotypes found in > 5 isolates only ; mit , miru vntr international type ; mdr , multidrug - resistant tuberculosis ( conventional resistance to isoniazid and rifampin ) ; na , not applicable .", "the cluster of s 256 ( miru profile 233325153325 ) was the most common among primary mdr tb isolates from yakutia and was fully 86% mdr ( table 1 ; technical appendix ) ." ], [ "this work characterizes severe isoniazid monoresistant and mdr tb in eastern siberia among patients with no history of tb treatment .", ". however , regionally specific genotypic patterns and resistance mutations were identified . as expected , in irkutsk primary mdr tb", "in eastern siberia , > 25% of primary tb was mdr , equivalent to the highest proportion reported from the russian federation ( 2 )", "was driven by strains of beijing lineage ( 5,6 ) . yet in the more geographically isolated population of yakutia , a strain previously unidentified in the russian federation , s 256 , had a miru profile recently found among canadian aboriginal populations ( 11 ) . in yakutia ," ], [ "phylogenetic trees of mycobacterium tuberculosis from patients with primary tuberculosis , yakutia and irkutsk , russian federation ." ] ]

[ [ "a total of 400 individuals from fpc syndrome families were genotyped and the frequencies of the founder mutations were compared with a set of healthy control subjects representative of the polish population .", "therefore , the aim of this study was to establish the prevalence of ten polish founder mutations in brca1 , chek2 , nbs1 , and palb2 among individuals from families with familial paca syndrome and to assess their possible association with the fpc risk in poland .", "the results of our previous case / control studies showed that these mutations in brca1 , chek2 , nbs1 , and palb2 are associated with the cancer risk at different sites of origin [ 4 - 12 ] .", "these syndromes arise as a result of germline mutations in the cdkn2a ( famm ) , stk11 ( peutz - jeghers syndrome ) , brca1 , brca2 , atm ( hboc ) , prss1 ( hp ) , mlh1 , and msh2 ( hnpcc ) genes .", "ten founder mutations in four cancer predisposing genes have been identified in poland [ 4 - 6 ] .", "a hereditary predisposition to different cancers , which is characteristic of the aforementioned genes , suggests that there could be a potential link between polish founder mutations and a predisposition to fpc ." ], [ "the study involved 400 probands from families with a diagnosis of fpc syndrome , who were either healthy individuals ( n=295 ) or fpc patients with cancer ( n=105 ) . table 1 lists the characteristics of the individuals included in the study . each of the 400 study participants came from a family , in which there were two or more cases of paca among the first - degree relatives .", "the recruitment of individuals for this study was conducted between 2002 and 2014 . the majority ( 80% ) were patients of our center , living in north - western poland , as well as in other cities of the country : biaystok , krakw , ld , olsztyn , opole , rzeszw , widnica , zielona gra , kielce .", "all ten mutations were analyzed successfully in 398 of the 400 fpc cases ( 99.5% ) .", "the two recurrent truncating mutations of palb2 ( 509_510delga and 172_175delttgt ) were detected using a taqman assay ( life technologies , carlsbad , ca ) using a lightcycler 480 real - time pcr system ( roche life science , mannheim , germany ) .", "sanger direct sequencing was undertaken to confirm the presence of mutations , using a bigdye terminator v3.1 cycle sequencing kit ( life technologies ) , according to the manufacturer s protocol .", "samples of cord blood from unselected infants were forwarded to the study center in szczecin ." ], [ "the study involved 400 probands from families with a diagnosis of fpc syndrome , who were either healthy individuals ( n=295 ) or fpc patients with cancer ( n=105 ) . table 1 lists the characteristics of the individuals included in the study . each of the 400 study participants came from a family , in which there were two or more cases of paca among the first - degree relatives .", "the recruitment of individuals for this study was conducted between 2002 and 2014 . the majority ( 80% ) were patients of our center , living in north - western poland , as well as in other cities of the country : biaystok , krakw , ld , olsztyn , opole , rzeszw , widnica , zielona gra , kielce .", "the mean age of the participants enrolled in this study was 49.44 years ( range , 19 to 91 years ) .", "a family history of cancer was taken either by the construction of a family tree or the completion of a standardized questionnaire .", "this study was conducted in accordance with the declaration of helsinki and all participants signed an informed consent document prior to donating the blood samples . furthermore , this study was approved by the ethics committee of the pomeranian medical university in szczecin , poland ." ], [ "the first consisted of 2,000 newborn children from 10 hospitals throughout poland ( szczecin , biaystok , gorzw , katowice , wrocaw , pozna , opole , ld , and rzeszw ) collected between 2003 and 2004 .", "the allele frequencies of the 10 alleles was computed separately for the adult and neonatal control groups and compared to determine if there were any differences in allele frequencies .", "a sample of dna was forwarded to the reference laboratory without any identifying information . to ensure comparability of the control groups ,", "samples of cord blood from unselected infants were forwarded to the study center in szczecin .", "the third group consisted of 1,000 adults from szczecin who submitted blood for paternity testing .", "the second group was taken from adult patient lists of three family doctors practicing in the szczecin region ." ], [ "the two recurrent truncating mutations of palb2 ( 509_510delga and 172_175delttgt ) were detected using a taqman assay ( life technologies , carlsbad , ca ) using a lightcycler 480 real - time pcr system ( roche life science , mannheim , germany ) .", "sanger direct sequencing was undertaken to confirm the presence of mutations , using a bigdye terminator v3.1 cycle sequencing kit ( life technologies ) , according to the manufacturer s protocol .", "all ten mutations were analyzed successfully in 398 of the 400 fpc cases ( 99.5% ) .", "the ivs2 + 1g > a and i157 t variants in chek2 were detected using restriction fragment length polymorphism pcr analysis , and the 1100delc mutation was analyzed using allelespecific oligonucleotide pcr .", "briefly , brca1 mutations , 4153dela and 5382insc were detected using the allele - specific oligonucleotide polymerase chain reaction ( pcr ) , and c61 g was detected using the restriction fragment length polymorphism pcr .", "the two that failed to be analyzed due to the poor quality of dna were discarded from statistical analysis .", "ten founder mutations in the brca1 , chek2 , nbs1 , and palb2 genes were genotyped , as described previously ." ], [ "the ors were generated from two - by - two tables and the statistical significance was assessed using a chi - square or fisher exact test with a yates correction ." ], [ "a founder mutation in one of the four genes studied was observed in 44 out of 398 fpc cases ( 11.06% ) and in 283 out of 4,000 controls ( 7.08% ) ( p=0.011 ; or , 1.56 ; 95% confidence interval , 1.12 to 2.18 ) .", "table 2 provides details of the prevalence of founder mutations studied among individuals from fpc families and in the population control group . in the group of all fpc individuals , the largest and statistically significant difference compared to the population control group", "two ( 5382insc , c61 g ) of the three polish founder brca1 mutations were detected in three of the 105 fpc cases with cancer ( 2.86% ) ( or , 6.72 ; p=0.006 ) compared to 17 of the 4,000 controls ( 0.42% ) .", "was observed for palb2 172_175delttgt ( 0.5% ; or , 10.05 ; p=0.048 ) . when the genotyping results were classified according to the health status of the probands , statistically significant differences were observed for the brca1 , palb2 and chek2 genes only in the group of fpc cases with cancer .", "palb2 mutations were observed in two of the 105 fpc cases with cancer ( 1.90% ) ( or , 9.52 ; p=0.014 ) compared to eight of the 4,000 controls ( 0.20% ) ." ], [ "this study observed a significant correlation between the prevalence of the polish founder mutation 172_175delttgt of palb2 gene and the fpc .", "in addition , an increased incidence of changes was observed in genes brca1 ( three founder mutation combined : p=0.006 ; or , 6.72 ) and chek2 ( four chek2 mutations combined : p=0.008 ; or , 2.26 ) , particularly the chek2 \n i157 t mutation ( p=0.03 ; or , 2.17 ) among the cancer - affected individuals from the fpc syndrome families . the fact that brca1 and palb2 mutations might be causative of fpc in a small subset of families is relatively new [ 14 - 16 ] .", "furthermore , the results are consistent with the observations that palb2 and brca1 mutations are reported in fpc , especially in the families with a history of breast cancer .", "breast cancer was also observed among the first degree relatives of one of the palb2 172_175delttgt and one of the brca1 5382insc mutation carriers from fpc .", "our previous study conducted among 383 paca patients reported that the polish founder mutation in nbs1 ( 657del5 ) is associated with an increased risk of paca ( or , 3.80 ; p=0.002 ) . while the results of the current study , including almost 400 cases from fpc families presented here , did not show a relationship between the nbs1 and fpc syndrome .", "the feature of the founder mutations in the chek2 gene is the multiorgan cancer risk among carriers ." ], [ "this case control study indicated that mutations in palb2 ( 172_175delttgt ) appear to increase the risk of fpc in heterozygous carriers from the polish population .", "in addition , the fpc risk appears to be increased in carriers of brca1 ( two of the three occurring : 5382insc , c61 g ) and chek2 founder mutations ( particularly chek2-i157 t missense variant ) .", ". studies in slavic and other populations should be performed to confirm this association and evaluate the utility of testing these genes for fpc in cancer genetic counselling .", "therefore , in the polish population , founder mutations in the genes , brca1 , palb2 , and chek2 , cause a small percentage of familial paca" ], [] ]

[ [ "in addition to being warm blooded , mammals also were adept at performing adaptive thermogenesis , giving them the ability to further increase their metabolic rates when conditions would otherwise result in hypothermia . from the perspective of humans in 2015 , it is easy to forget that thermoregulation , in all of its dimensions , was a critical part of mammalian history", "in addition , there are examples of experiments in mice where certain mutations have caused very robust increases in energy expenditure and thermogenesis , but where the levels of ucp1 mrna and protein are unchanged .", "adaptive thermogenesis can also be activated directly by cold in beige adipocytes and by other stimuli that may signal independently from the -adrenergic receptors .", "thermogenesis comes from chemical reactions in which the liberated free energy is not captured in other molecules ( e.g. , atp or creatine phosphate ) or used for work .", "this process is typically thought of as being indirectly activated by cold , via the sympathetic nervous system ( sns ) ." ], [ "thus , it appears that both thermogenic cell types depend on prdm16 , but , at least in early life , the classical brown fat has a second factor that can support development , prdm3 .", "the role of prdm16 in the classical brown fat in vivo is interesting and somewhat more complex .", "ucp1 brown fat has long been known to occur in two distinct anatomical locations in rodents .", "consistent with this , primary cultures of classical brown fat express low levels of certain genes characteristic of skeletal muscle ( 11 ) .", "however , fat cells are also able to directly sense cold , though the mechanism is not well understood ( 9 ) . in both anatomical situations , brown fat cells have multiple small lipid droplets , numerous mitochondria , and rich innervation and vascularization . despite these similarities , it is now clear that the classical brown fat cells and the inducible beige fat cells come from different developmental lineages and are , in fact , distinct cell types ." ], [ "the nuclear hormone receptor peroxisome proliferator activated receptor ( ppar ) is necessary and sufficient for the development of all fat cells ( 21 ) .", "a number of other factors have also been shown to play roles in this biology , but a comprehensive review is beyond the scope of this article .", "harnessing the therapeutic potential of brown and beige fat requires a detailed understanding of the molecular mechanisms responsible for the determination and maintenance of each cell type ." ], [ "the combination of insufficient hair , fur , and insulation , along with a high body surface area - to - mass ratio make babies and small mammals particularly susceptible to hypothermia . as a result", "until fairly recently , brown fat was thought to be present in meaningful amounts only in human infants and small mammals .", ", they have developed significant interscapular brown fat , which defends body temperature by adaptive thermogenesis .", "research has increasingly suggested that adult human brown fat shares features of the inducible beige fat described in rodents .", "these studies made use of [ f]-fdg pet to confirm that adults have glucose - avid tissue with imaging characteristics of adipose in deposits in the supraclavicular and spinal regions . as assayed by [ f]-fdg pet ," ], [ "as a deeper understanding of brown and beige fat has emerged , researchers have turned to strategies to induce the activity of these tissues as a possible therapy for obesity and metabolic diseases .", "an increasing understanding of the relevant modifications of prdm16 and the upstream signaling pathways involved may provide new opportunities for therapeutic targeting of brown and beige fat .", "a recent publication ( 42 ) described the development of controlled - release mitochondrial protonophores that can apparently safely uncouple in the liver , and in rats these compounds can improve insulin resistance , diabetes , hypertriglyceridemia , and hepatic steatosis .", "mouse studies suggest that prdm16 is a key control point in brown and beige fat phenotype ." ] ]

[ [ "in a recent issue of critical care , meyer and colleagues report interesting surveillance data from icus in 30 german hospitals , based on a large amount of microbiology and pharmacy data gathered between 2001 and 2008 .", "one of the main study findings is a decreasing rate of methicillin - resistant staphylococcus aureus ( mrsa ) and a dramatic increase of third generation cephalosporin ( 3gc ) resistant enterobacteriaceae over the study period . in recent years", "the current study confirms this worrisome finding and also shows an increase in carbapenem , 3gc and fluoroquinolone use in german icus with a stable volume of overall antibiotic use .", "the latter two antibiotic classes have been repeatedly identified as risk factors for carriage of multidrug resistant gram - negatives .", "the fact that two icus in 2008 reported carbapenem resistant k. pneumoniae in the current study raises the concern that these strains might already be more common in central europe than previously assumed since detection of these strains may be difficult with routine laboratory techniques ." ], [ "3gc : third generation cephalosporin ; esbl : extended - spectrum betalactamase ; mrsa : methicillin - resistant staphylococcus aureus ." ], [], [ "preparation of this commentary was supported in part by the 6th and 7th framework programme of the european community in the context of the projects ' changing behaviour of health care professionals and the general public towards a more prudent use of anti - microbial agents ' ( champ , contract sp5a - ct-2007 - 044317 ) and ' impact of specific antibiotic therapies on the prevalence of human host resistant bacteria ' ( acronym saturn , agreement fp7-health-2009-n241796 ) ." ] ]

[ [ "primary malignant tumors of the hypopharynx are predominantly squamous cell carcinomas ( sqccs ) , as primary small - cell carcinoma ( smcc ) of the hypopharynx is rare .", "we herein report a the case of a patient with primary combined smcc with an sqcc element and investigate the expression of specific proteins for molecular - targeted therapy .", "combined primary smcc and sqcc of the hypopharynx , referred to as composite tumor of the hypopharynx , is even more rare , with only 3 cases previously reported ( 13 ) ." ], [ "to predict the prognosis of this patient , we evaluated the expression of epidermal growth factor receptor ( egfr ) .", "furthermore , to evaluate the possibility of using molecular - targeted therapy for combined smcc and sqcc , the expression of proteins such as platelet - derived growth factor receptor ( pdgfr ) , vascular endothelial growth factor receptor 2 ( vegfr2 ) and kit was examined .", "our case was negative and not considered as a high - risk hpv status ( fig .", "comparison of this sequence variation with the single - nucleotide polymorphism ( snp ) database revealed the presence of a known snp at codon 567 of pdgfr ( 9 ) .", "the hpv status was determined using the hpv typing set ( takara bio . , tokyo , japan ) , a pcr primer set specifically designed to identify hpv genotypes 16 , 18 , 31 , 33 , 35 , 52 and 58 in genomic dna .", "on immunohistochemical analysis , the smcc element was strongly positive for kit and pdgfr ; however , egfr and vegfr2 were not expressed ( fig .", "the sqcc element was mildly positive for pdgfr and egfr ; however , kit and vegfr2 were not expressed ( fig ." ], [ "furthermore , to evaluate the possibility of using molecular - targeted therapy for combined smcc and sqcc , the expression of proteins such as platelet - derived growth factor receptor ( pdgfr ) , vascular endothelial growth factor receptor 2 ( vegfr2 ) and kit was examined .", "we observed 2 components in the lesion : a poorly differentiated sqcc and a small - sized smcc with finely granular , hyperchromatic nuclei , inconspicuous nucleoli and scanty cytoplasm .", "microscopic sections from the larynx revealed a combined tumor , composed predominantly of smcc localized in the upper side and sqcc localized in the lower side ( figs . 1 and 2a ) .", "the metastatic potential of the lesion was further supported by the smcc component found to infiltrate lymphatic vessels ( fig .", "diffuse cd56 positivity in the smcc component in the cervical lymph nodes supported the histological diagnosis ( fig .", "immunoreactivity to ki-67 was seen in the nuclei of tumor cells . in the smcc component ," ], [ "microscopic sections from the larynx revealed a combined tumor , composed predominantly of smcc localized in the upper side and sqcc localized in the lower side ( figs . 1 and 2a ) .", "we observed 2 components in the lesion : a poorly differentiated sqcc and a small - sized smcc with finely granular , hyperchromatic nuclei , inconspicuous nucleoli and scanty cytoplasm .", "furthermore , to evaluate the possibility of using molecular - targeted therapy for combined smcc and sqcc , the expression of proteins such as platelet - derived growth factor receptor ( pdgfr ) , vascular endothelial growth factor receptor 2 ( vegfr2 ) and kit was examined .", "the metastatic potential of the lesion was further supported by the smcc component found to infiltrate lymphatic vessels ( fig .", "diffuse cd56 positivity in the smcc component in the cervical lymph nodes supported the histological diagnosis ( fig .", "the tumor extended superiorly to involve the right supraglottis and exhibited variable gross morphology , ranging from ulcerated , to nodular , to plaque - like growth ." ], [ "comparison of this sequence variation with the single - nucleotide polymorphism ( snp ) database revealed the presence of a known snp at codon 567 of pdgfr ( 9 ) .", "tokyo , japan ) , a pcr primer set specifically designed to identify hpv genotypes 16 , 18 , 31 , 33 , 35 , 52 and 58 in genomic dna .", "our case was negative and not considered as a high - risk hpv status ( fig .", "analysis of exon 12 of pdgfr from other normal tonsillar tissues revealed a similar ag change at the 1849 nucleotide position .", "genomic dna was extracted from frozen tumor specimens using the qiaamp dna mini kit ( qiagen , hilden , germany ) , according to the manufacturer 's protocol . a molecular genetic analysis of kit ( exons 9 , 11 ,", "13 and 17 ) and pdgfr ( exons 12 , 14 and 18 ) was performed using the polymerase chain reaction ( pcr ) direct sequencing method , as previously reported ( 58 ) ." ], [ "combined smcc of the larynx has only been reported in 17 cases in the literature to date .", "combined smcc of the hypopharynx is extremely rare and is often difficult to pathologically diagnose prior to surgical treatment .", "to the best of our knowledge , a molecular - targeted therapy for treating combined smcc of the hypopharynx and larynx has not yet been reported .", "multi - modality therapy should be performed for combined smcc of the head and neck region .", "moreover , the majority of the patients succumbed to the disease within 2 years of diagnosis , even with adjuvant radiation and chemotherapy ( 1214 ) . despite the rarity of these tumors , the clinical behavior of combined smcc of the larynx appears to be similar to that of the hypopharynx .", "our case is the first to report kit and pdgfr expression in combined smcc in the hypopharynx and larynx ; if similar results are obtained from larger series , these data may have management and prognostic implications through the possible use of targeted biological therapy in these tumors . at present ,", "metastasis from a primary lung smcc must be carefully distinguished from a primary hypopharyngeal or laryngeal smcc by imaging studies of the lung ( 15 ) . in this case ," ] ]

[ [ "the bvdv gbk strain is an adventitious bvdv2 isolated from cells of the bovine kidney cell \n line gbk .", "( a ) four amino acid substitutions , d136 g , i2623v , d3148 g and \n d3502y , were found in the gbk_e virus in comparison with the \n gbk_e virus .", "( a ) four amino acid substitutions , d136 g , i2623v , d3148 g and \n d3502y , were found in the gbk_e virus in comparison with the \n gbk_e virus .", "measurements of type i interferon production in bvdv - infected cells were performed using a \n previously described plaque reduction method with vsv as a challenge virus , with some modifications . in brief , the supernatants \n from bvdv - infected cells were inactivated by exposure to uv light ( 254 nm ) in the uv \n crosslinker ( atto corporation , tokyo , japan ) under the condition of 500 mj / cm . \n", "( b ) three recombinant viruses with combinations of amino \n acid substitutions were generated in the gbk_e backbone by site - directed \n mutagenesis and in - fusion techniques .", "cloning of a pair of end and end viruses from viral \n stocks : a reverse plaque formation technique was used to obtain a pair of end and end viruses from \n viral stocks as described previously .", "the full - length genome \n amplification strategy was employed to obtain a \n full - length pcr amplicon for in vitro rna transcription ." ], [ "cloning of a pair of end/ end viruses from the bvdv gbk \n strain and determining their whole genome sequences : a pair of end \n and end viruses ( gbk_e and gbk_e , respectively ) was \n cloned from the bvdv gbk strain by means of reverse plaque formation techniques and limited \n dilution .", "detection of irf-3 in cells infected with the parental or mutant viruses : \n to investigate the expression levels of irf-3 in bvdv - infected cells , irf-3 in the lysates \n of bfm cells infected with gbk_e , gbk_e , vgbk_e or one \n of the three mutant viruses was detected by western blotting ." ], [ "our results indicate that a single mutation in the trash motif at position \n 136 of bvdv n abolishes its interaction with bovine irf-3 and halts the \n degradation of irf-3 .", "we cloned a pair of \n end and end viruses ( gbk_e and gbk_e ) from \n the bvdv gbk strain using reverse plaque formation techniques [ 5 , 19 ] .", "this result demonstrates that the single aspartic acid residue in the \n zinc - binding trash motif of n , which occurs at position 136 of the genome of \n the gbk_e virus , is the key to determine viral capacity to inhibit type i \n interferon production and display the end phenomenon .", "moreover , the mutation of the amino acid residue at position 136 of \n gbk_e restores its function as an interferon antagonist , as shown for csfv . \n" ] ]

[ [ "golden \n delicious , were the first isoforms for which the dna sequence \n was determined and are identical at the amino acid level . here", "immunologic investigations of naturally \n occurring mal d 1 isoforms revealed only small differences of their \n ige binding capacities and it appears that divergent allergenicities \n of apple strains are predominantly determined by different mal d 1 \n expression levels . whereas the \n immunological properties of mal d 1 suggest that this \n protein has a three - dimensional structure and ige binding epitopes \n that are similar to those of bet v 1 and other members of the pr-10 \n protein family , experimental structural data for mal d 1 have not \n been available to date . as a first step toward structural characterization , \n we recently assigned the nmr backbone and side chain h , c , and n chemical shifts of the isoform mal \n d 1.0101 .", "along with mal d 1.02 , and depending on the cultivar , isoforms from \n the mal d 1.01 cluster are by far the most abundant isoforms found \n in apples . within the mal d 1.01 cluster , \n", "mal d 1 is encoded by a multigene family , \n and a number of isoforms \n of mal d 1 have been identified to date , which are clustered into \n four groups on the basis of their dna sequence similarities , that \n is , mal d 1.01 , mal d 1.02 , mal d 1.03 , and mal d 1.04 .", "pcr screening and mass spectrometric studies \n showed that mal d 1 isoforms are not cultivar specific and that mixtures \n of isoforms are present in apple fruits ." ], [ "the dna of mal d 1.0101 ( genbank nucleotide \n code x83672 , protein code caa58646 ) was cloned into the expression vector pet28b \n by using the restriction sites ncoi and xhoi .", "the coordinates \n of the mal d 1.0101 structures were deposited in the protein data \n bank under the accession code number 5mmu .", "were included for backbone amide protons , if the n edited noesy - hsqc spectra did not show a water exchange \n cross peak . of 100 generated structures , the 20 lowest energy structures \n were picked and further refined in explicit solvent with the amber14 \n simulation package using pmemd.cuda and the amber force field 99sb - ildn . each structure was soaked into a truncated octahedral \n solvent box of tip3p water molecules with a minimum wall distance \n of 10 . for the refinement , hydrogen atoms and water molecules \n were minimized with fixed heavy atoms . the temperature was increased \n from 0 to 300 k , where the structures were simulated using the noe \n distance restraints , minimized again , and validated using the protein \n structure validation software ( psvs ) suite ( table 1 ) .", "nmr resonance assignments of mal d 1.0101 were made using standard \n triple - resonance methods and were deposited \n at the biological magnetic resonance data bank ( bmrb ) under accession \n no .", "nmr data were processed using nmrpipe and analyzed with ccpnmr . for measuring protein translational diffusion , we \n employed a stimulated \n echo pulsed field gradient nmr experiment .", "construct integrity was ensured by \n dna sequencing ( microsynth ag , balgach , switzerland ) , and the protein \n was expressed in escherichia coli bl21 \n star ( de3 ) .", "experimental details were identical to those reported for bet v \n 1 . for the determination of the hydrodynamic \n radius of mal d 1.0101 , we used dioxane as a standard reference under \n identical buffer conditions , assuming a hydrodynamic radius of 2.12 \n ." ], [ "epitope grafting \n was used to characterize the role of the bv16 epitope in mal d 1 by \n recreating this epitope on the mal d 1 surface , confirming its importance \n for ige binding and cross - reactivity with bet v 1 . in an orthogonal approach , several mal d 1 stretches encompassing \n residues that are crucial for ige binding were transferred to bet \n v 1 to investigate the role of these structural segments for cross - reactivity , and chimeras of bet v 1 and mal d 1 were created \n to map the epitope of a human monoclonal ige , which was isolated from \n a phage library , to the c - terminus of bet v 1 . in addition , epitope grafting provides access to chimeric \n allergens with fine - tuned antigenic properties , such as reduced ige \n binding capacitites , for molecule - based allergy diagnosis and specific \n immunotherapy .", "in addition , grafting of conformational \n epitopes by transferring stretches of residues between homologous \n allergens has become a valuable experimental tool .", "the three - dimensional \n structure of mal d 1.0101 presented here provides the biophysical \n basis for elucidating the molecular details of immunological cross - reactivity \n in great detail .", "these data thus \n provide a structural rationale for the observed allergic cross - reactivity \n between birch pollen and apple allergens .", "it is clear that high - resolution structural data provide \n the basis \n to determine and compare structural details of ( cross - reactive ) binding \n epitopes in allergenic proteins .", "knowledge of the structural \n details of these allergens elements is required to generate correctly \n folded chimeras , because transfer of ( partly ) mismatching stretches \n of secondary structure between different allergens may well be the \n reason for a loss of protein fold and , consequently , reduction of \n ige - binding capacities ." ] ]

[ [ "head and neck oncological resections may result in composite oro - mandibular defects involving the oral mucosa ( lining ) , mandibular bone and the skin ( cover ) .", "existing literature , however , provides conflicting views about the use of a particular side and orientation of the fibula flap for achieving the optimal outcome .", "there is always a possibility of using the bone flap in a more efficient fashion for the reconstructive need .", "the purpose of this study is to confirm anatomically the effect of bone , soft tissue and vessel orientation on the ease of doing reconstruction .", "anatomically , the fibula bone has a triangular cross section , it has a lateral surface where peroneal muscles are attached , this is a broad flat surface and is ideal for fixing the reconstruction plate during mandibular reconstruction , at the lower end of this peroneal surface is the posterior crural septum through which the peroneal artery perforators supplying the skin paddle run , this septum has variable length and mobility , which determines the movement of the skin paddle . on the posterior and medial facet of this triangle , originates the flexor hallucis longus ( fhl ) muscle and on the supero - medial aspect is the origin of the tibialis posterior muscle and between these two run the vascular pedicle . due to this unique three - dimensional anatomy", "we also propose an algorithm for choosing the correct side of the fibula for a particular reconstructive need and at the same time minimising the donor side morbidity ." ], [ "following variables were considered : \n placement of the vascular pedicle the pedicle needs to be placed anteriorly if the microvascular anastomosis is to be done on the opposite side due to vessel paucity in the ipsilateral neck.type of associated soft tissue defect ", "composite fibula flaps of the same dimension were harvested from both legs of a fresh cadaver .", "the harvested flaps were used to reconstruct the mandibular defect in different orientations , and the best configuration for each reconstructive requirement was assessed .", "the defect could be a mucosal defect ( lining ) , the skin defect ( cover ) or a combined mucosa and skin defect . \n ", "the pedicle needs to be placed anteriorly if the microvascular anastomosis is to be done on the opposite side due to vessel paucity in the ipsilateral neck .", "the defect could be a mucosal defect ( lining ) , the skin defect ( cover ) or a combined mucosa and skin defect ." ], [ "keeping the peroneal surface for plating , that is , facing outwards , four different configurations of the fibula flap are possible for a given mandibular defect . implications of each one for reconstruction are discussed below .", "contralateral fibula with pedicle posterior this configuration leads to a tissue orientation similar to that discussed in point 1 ( ipsilateral fibula flap placing vascular pedicle posterior and thus is not particularly suited for intra oral reconstruction and skin paddle is best utilised outside [ figure 4 ] .", "ipsilateral fibula with pedicle anterior the fhl muscle is supero - medial to the bone and lies within the oral cavity thus it can be easily utilized for intraoral lining ." ], [ "ipsilateral fibula with pedicle posterior the fhl muscle lies at the submandibular region with the vascular pedicle lying on its superior aspect and therefore pulling the muscle inside for intraoral reconstruction kinks the vascular pedicle .", "the skin paddle comes out from the lower and outer border of the reconstructed mandible because of the anatomical position of the posterior crural septum [ figure 1 ] . if this skin paddle has to be taken inside the oral cavity , it has to travel over the plated surface of the fibula , which wastes about 3 - 4 cm of skin paddle width .", "the length of the posterior crural septum being variable also restricts the inside movement of the skin paddle ." ], [ "ipsilateral fibula with pedicle anterior the fhl muscle is supero - medial to the bone and lies within the oral cavity thus it can be easily utilized for intraoral lining .", "in this situation , the septum location becomes superior and medial in relation to the bone .", "hence , the skin paddle does not have to go around the bone to come inside and thus we do not lose skin paddle width when we turn it inside .", "it can thus be used for providing mucosal lining more easily . for moving the skin paddle outside to provide skin cover , it has to travel over the plated surface of the fibula although the wastage of skin paddle width is not much [ figure 2 ] ." ], [ "this configuration leads to a tissue orientation similar to that discussed in point 2 ( ipsilateral fibula flap placing the vascular pedicle anterior and thus is suited for intra oral reconstruction [ figure 3 ] ." ], [ "this configuration leads to a tissue orientation similar to that discussed in point 1 ( ipsilateral fibula flap placing vascular pedicle posterior and thus is not particularly suited for intra oral reconstruction and skin paddle is best utilised outside [ figure 4 ] ." ], [ "of all the reconstructive options available for the complex mandibular defect , the free fibula osteo - cutaneous flap is the most widely used one", ". however , there is conflicting literature regarding the ideal donor side of the fibula .", "an anteriorly placed pedicle may be considered in case of a vessel depleted neck or for a ramus reconstruction , when one needs to reconstruct ramus of the mandible and plans to keep the vascular pedicle posteriorly , there is a possibility of acute kink of the vessels if we choose to anastomose the vessels in the neck and if we choose to anastomose the vessels with superficial temporal vessels , one has to grapple with the problem of size mismatch between the donor and recipient vessels with an increased potential of failure . in other situations ,", "put forth that there is no donor side specificity of fibula free flap for complex oro - mandibular reconstruction ." ], [ "if the pedicle is positioned anteriorly , such a defect would be adequately reconstructed with an ipsilateral fibula with the fhl muscle ( as described in point 2 ) .", "the donor area skin can be closed primarily because no skin is harvested . in a posteriorly placed pedicle ," ], [ "when the pedicle is positioned anteriorly , such a defect would need an ipsilateral fibula with optimal sized skin paddle ( as described in point 2 ) .", "the skin paddle may be used to cover the skin defect and the fhl muscle for reconstructing the mucosal defect . however , if the size of the defect is beyond the dimension which could be covered by fibula , such defects are reconstructed with double flaps using the fibula skin paddle for one defect and a second free / regional flap for the other defect .", "buccal mucosal defect extending to the upper alveolus and secondary reconstructions of the mandible would necessitate a contralateral neck anastomosis .", "the donor area skin may be closed primarily , with a soleal propeller flap or skin graft . in a posteriorly placed pedicle ,", "this concept enables us to reduce the donor site defect by choosing the side of fibula flap , which has the skin paddle that will fall into an anatomically correct position to reconstruct the soft tissue defect ." ], [ "these defects are most optimally reconstructed with the ipsilateral fibula if the pedicle has to be brought posteriorly ( point 1 ) or with the contralateral fibula if the pedicle has to be brought out anteriorly ( point 4 ) ." ], [ "such defects can be reconstructed with a configuration described in points 2 and 3 . the skin paddle may be used to cover the skin defect and the fhl muscle for reconstructing the mucosal defect . however , if the size of the defect is beyond the dimension which could be covered by fibula , such defects are reconstructed with double flaps using the fibula skin paddle for one defect and a second free / regional flap for the other defect .", "this concept enables us to reduce the donor site defect by choosing the side of fibula flap , which has the skin paddle that will fall into an anatomically correct position to reconstruct the soft tissue defect .", "closure of smaller defects primarily or with propeller flaps result in superior aesthetic outcome [ figures 5 and 6 ] ." ], [ "the algorithm based selection of appropriate sided fibula flap facilitates complex mandibular reconstruction by placing the right kind of tissue at the right place and helps in reducing the donor site morbidity by allowing the surgeon to harvest only the required amount of skin ." ] ]

[ [ "therefore , we intended to analyze the effect of -511 c / t polymorphism on il - i secretion from lps - induced lymphocytes in an attempt to reveal the possible role of this particular polymorhism in the etiopathogenesis of mtle - hs .", "mesial temporal lobe epilepsy with hippocampal sclerosis ( mtle - hs ) is the most common type of partial or localization - related seizure disorder in humans .", "there is increasing evidence to support the role of il-1 in reducing seizure threshold and epileptogenesis in the pilocarpine status epilepticus model of epilepsy .", "mesial temporal sclerosis ( mts ) with prominent neuronal loss and gliosis in the hippocampus is the most common pathology in temporal lobe epilepsy ( tle ) .", "although the pathogenesis and epileptogenesis of hippocampal sclerosis ( hs ) has been studied for years , the information available so far still does not fully explain the situation ." ], [ "diagnosis of mtlehs was based on clinical history , electroencephalography , magnetic resonance imaging , and , in some patients , on histopathological findings after the selective amgydalahippocampectomy and anterior temporal lobectomy .", "thirty patients with mtle - hs admitted to the akdeniz university hospital neurology department , turkey , were enrolled in this study .", "the -511 region of il-1 gene has been genotyped with polymerase chain reaction - restriction fragment length polymorphism ( pcr - rflp ) using 2 mg of genomic dna as template . by using the primers for -511 c / t polymorphism described below", "pcr products acquired from those with a cc genotype were cleaved into two fragments of 190 and 114 bp by ava i enzyme , whereas the pcr products of people with tt genotype was not digested at all , yielding a product of 304 bp .", "dna was extracted from blood samples using the robotic system magnapure ( roche ) and the amount of dna was measured by spectrophotometer .", "peripheral venous blood samples ( 3 ml ) were collected from each subject into vacutainer tubes containing edta .", "oligonucleotides used for pcr : forward primer : 5-tggcattgatctggttcatc reverse primer : 5-gtttaggaatcttcccactt peripheral blood of patients and healthy individuals was drawn into heparinized tubes , and lymphocytes were isolated with a density gradient method and pipetted into plates ( 210 cells each well ) and incubated for 24 h ( 5% co2 , 37c ) in an rpmi 1640 culture medium including 10% fcs with ( 0.5 ng / ml ) or without lps . the cells were precipitated by centrifuge at 1600 rpm for 10 min after 4 and 24 h. the supernatants were transferred to another tube and stored at 80c until elisa analyses ." ], [ "diagnosis of mtlehs was based on clinical history , electroencephalography , magnetic resonance imaging , and , in some patients , on histopathological findings after the selective amgydalahippocampectomy and anterior temporal lobectomy .", "a control group of 32 healthy volunteers with matching age , gender ratio and ethnic origins was also included .", "the control subjects had no history of seizures or neurological disorders and no central nervous system or other infections at the time of blood sample collection .", "thirty patients with mtle - hs admitted to the akdeniz university hospital neurology department , turkey , were enrolled in this study ." ], [ "pcr products acquired from those with a cc genotype were cleaved into two fragments of 190 and 114 bp by ava i enzyme , whereas the pcr products of people with tt genotype was not digested at all , yielding a product of 304 bp .", "the -511 region of il-1 gene has been genotyped with polymerase chain reaction - restriction fragment length polymorphism ( pcr - rflp ) using 2 mg of genomic dna as template . by using the primers for -511 c / t polymorphism described below ,", "dna was extracted from blood samples using the robotic system magnapure ( roche ) and the amount of dna was measured by spectrophotometer .", "the gels were stained with ethidium bromide and the dna fragments were visualized by an uv transluminator .", "each pcr product was then cleaved by ava i enzyme and the digested pcr products were subjected to agarose gel electrophoresis .", "peripheral venous blood samples ( 3 ml ) were collected from each subject into vacutainer tubes containing edta ." ], [ "peripheral blood of patients and healthy individuals was drawn into heparinized tubes , and lymphocytes were isolated with a density gradient method and pipetted into plates ( 210 cells each well ) and incubated for 24 h ( 5% co2 , 37c ) in an rpmi 1640 culture medium including 10% fcs with ( 0.5 ng / ml ) or without lps . the cells were precipitated by centrifuge at 1600 rpm for 10 min after 4 and 24 h. the supernatants were transferred to another tube and stored at 80c until elisa analyses .", "il1 levels in cell culture supernatants were studied according to the manufacturer s protocol ( ebioscience , cat . n. 88 - 7010 ) ." ], [ "tests for differences in allelic and genotypic frequencies were performed using 2 test and fisher s exact test .", "all statistical analysis was carried out using statistical package for social sciences ( spss ) windows version 15.0 ( spss inc . ," ], [ "since il-1-511 t allele has been suggested to be associated with increased in vitro production of il-1 and that il-1 is involved in hs pathogenesis , we also analyzed the il-1 secretion between the patients and control individuals who carry the t allele at position -511 of the il-1 gene .", "there was no significant difference between the mtle - hs patients and controls according to genotype and allele frequencies of il-1-511 .", "in addition , despite the fact that both spontaneous and stimulated secretion levels of il-1 were higher in mtle - hs patients who carry the t allele with respect to those patients who do not , the difference was not statistically significant ( figure 2 ) .", "levels of secreted il-1 from the cultured lymphocytes incubated either with or without lps were measured at three different time frames during the culture period ( basal , 4 h and 24 h ) .", "however , although spontaneous secretion levels of il-1 were higher in mtle - hs patients , there was no significant difference between the groups ( figure 1 ) ." ], [ "in this study , we found that neither the il-1 -511 c / t polymorphism nor the secreted il-1 from the cultured lymphocytes were associated with mtle - hs in a group of turkish patients . in our study , the average age of onset of seizures and gender were similar to those presented in other studies . on the other hand ,", "cytokine levels in peripheral blood seem to reflect the central nervous system s production of cytokines , but these are not always correlated .", "thus , besides ( -511 ) polymorphism , a combination of different haplotypes and many other transcription factors binding to different sites should impinge on the transcriptional activity . in conclusion , in experimental studies , activation of cytokines has been observed especially in areas of onset of seizures and spreading of discharge . in clinical studies ,", "il-1-511 t single nucleotide polymorphism has been thought to be associated with mtlehs and febrile seizures .", "previously showed no association between il-1 gene polymorphism and tle with hs in turkish ancestry in a larger group ." ] ]

[ [ "this study was therefore designed to investigate the subjective ratings of dental anxiety levels among dental , medical and engineering jordanian university students .", "lack of educational courses specialized in increasing dental awareness amongst non - dental university students in jordan , in addition to shortage of information about correlation between field of study and dental anxiety levels in the dental literature have raised the idea of investigating the level of dental anxiety among the different student populations .", "in addition , the present study aimed to explore the sources of dental anxiety and the impact of gender on the perceived dental anxiety .", "the presence of high levels of dental anxiety amongst dental care seekers yielded patients with negative attitudes towards dental treatment and rendered dental treatment more difficult to accomplish successfully4,16 .", "the modified dental anxiety scale will be , therefore , used to measure dental anxiety in the current study .", "dental anxiety might also affect patient - dentist relationship and obscure proper diagnosis of the actual dental problem8,25 ." ], [ ". however , the modified version of das was used21 where an extra item has been included referring to the respondent 's feelings toward local anesthetic injection with especial reference to the site of the injection , because the pain experienced with local anesthetic injections varies according to its location in the mouth14 .", "anxiety related to dental treatment was assessed by means of corah 's dental anxiety scale ( das )", "the scores for each of the 5 item responses were summed up to give an estimated value of dental anxiety .", "statistical significance was based on the probability values of p= 0.05 . furthermore , as a total score of 15 or more almost indicates highly anxious patient19 , the frequencies of subjects with a score of 15 or more in the 3 student groups were also reported .", "the questionnaire was distributed to the third to fifth year undergraduate dental , medical and engineering students at the jordan university of science and technology .", "if you were about to have a local anesthetic injection in your gum , how would you feel ?" ], [ "the total number of the participants in the current study was therefore 535 , which accounts for a response rate of 89.2 percent .", "surprisingly , medical students were found to be the most frequent among those who scored 15 or above .", "table 2 presents the means and standard deviations of individual items and total scores of the modified corah dental anxiety scale with the results of one - way anova analysis comparing the various groups based on the field of study . out of the several anxiety scale items , the highest anxiety score ( 3.4 )", "however , there were no statistically significant differences between medical and engineering students in relation to these items ( table 2 ) .", "as expected , dental students scored the lowest total dental anxiety scores ( table 2 ) which were significantly lower than those scored by either medical or engineering students ( f = 14.13 , p = 0.00 ) ." ], [ "this study revealed that dental students do have lower levels of dental anxiety than their engineering and medical counterparts ( p < 0.01 ) .", "presence of suitable dental health education and knowledge seems to be capable , to some extent , of overruling the effect of stress and personality factors on dental anxiety among dental students .", ", it appears that further dental health education measures are required to be applied among the jordanian non - dental university students and the population in general in order to control the levels of dental anxiety and thus improve patient dental attitudes and compliance .", "pre - university as well as non - dental university curricula should include dental health education in order to help reduction of dental anxiety among the population .", "the mean total scores for the mdas showed that severe dental anxiety was mostly associated with drilling and intraoral local anesthetic injection .", "suitable standards of dental health knowledge and education could overcome the negative effects of personality and reduce dental anxiety ." ], [ "although the current study utilized the modified anxiety scale and investigated the levels of dental anxiety among university students from different fields of study and the sample size was representative and large , further studies are required to investigate the effect of various correlates on dental anxiety ." ] ]

[ [ "we report a case of ten which was induced by multiple drugs some of which have been rarely implicated in the causation of ten .", "toxic epidermal necrolysis ( ten ) is a rare life threatening idiosyncratic mucocutaneous drug reaction characterized by widespread epidermal necrosis followed by epidermal detachment .", "drug - induced ten is the commonest cause and antiepileptics , antibiotics , nonsteroidal anti - inflammatory drugs ( nsaids ) and allopurinol are the most commonly implicated agents . here" ], [ "a 42-year - old woman was referred to medical emergency with extensive epidermal detachment and ocular , genital , and oral lesions of 5 days duration leading to a diagnosis of toxic epidermal necrolysis ( ten ) .", "the patient showed steady improvement with the therapy given and was discharged , after 8 days , without any sequelae .", "seven days prior to this admission , she had presented to a general practitioner with symptoms of vertigo , anxiety , and restlessness . although no provisional or differential diagnosis was found in the documents provided by the patient , she was prescribed antihistamines ( cinnarizine and dimenhydrinate ) , paracetamol / metoclopramide combination and multivitamins ." ], [ "this is most likely a case of drug - induced ten as other causes like upper respiratory tract infection , viral infection , or malignancy were not present .", "there have been no case reports of ten due to a combination of both the drugs , nor have there been any reports regarding ten being caused by antihistamines or multivitamins .", "there have been two case reports of ten caused by paracetamol and a case control study showing increased risk of sjs or ten with paracetamol use .", "as this was an acute presentation , which occurred right after the drugs were administered , systemic lupus erythematosus ( sle ) and rheumatological disorders were ruled out ." ], [ "ten in this patient was probably caused by paracetamol and metoclopramide , but a possibility of an interaction as well as the role of other drugs can not be ruled out ." ] ]

[ [ "i feel strongly that seeing cell structures at the em level still is the only way to fully grasp their molecular architecture , and that seeing changes in their molecular architecture at this level is the only way to truly understand their function .", "helping to eclipse the routine em that i enjoyed so much have been all the tremendous advances in light microscopy , coupled with all the advances in digital camera recording of live - cell dynamics ( not to mention the burgeoning field of superresolution light microscopy , crowned this year with the nobel awards ) .", "the result was our so - called liquid helium cooled cryopress ( renamed to avoid the distressing idea of a delicate piece of tissue being slammed against anything albeit , it 's the abruptness of contact and the superfast extraction of heat from the sample by the copper block that gives such good freezing in the first place ) . fast - forward to today , and we find that freeze substitution is still the backbone of modern efforts to image cells in the electron microscope , and indeed preserves the structure of cells far better than the techniques of fixation and plastic embedding developed by the pioneers of thin - section em . when combined with thicker sections , higher em voltages , and modern tomographic reconstruction techniques , it yields really outstanding images .", "after hyping deep - etch electron microscopy ( em ) for my whole career ( heuser , 2011 ) , i 'll take this invitation to write an ascb award essay to talk it up some more !", "people not familiar with em should be reminded that porter 's 1945 images opened the door to cell biology , and his development of thin - sectioning techniques for cells in the following 10 years really put cell biology on the map . but back to replicas ." ], [ ", pietro will love that huge neuromuscular junction ; fulvio will be amazed by that quality of membrane preservation in freeze - substituted yeast ; ursula will be psyched by that run of axonemal dynein ; tom will be impressed with such a clear view of actin branchpoints . ", "it 's for showing to someone who immediately comes to mind as soon as that field pops into view in the electron microscope . oh", "maybe a new postdoc or a close collaborator who really needs to look over my shoulder to see how his or her prep came out . anyway , i want each of my real or imaginary viewers to like that picture , to think it 's a good picture attractive , clear , understandable , useful , illuminating , that is , illuminating something about the subject ( be it a personal portrait or a picture of a cell interior or a molecule ) .", "( of course , they 're not actually there , they may be continents away , but i 'm imagining them being there and already planning how i will get that picture to them and what i 'll tell them about it as soon as it 's in the computer . )", "i want my audience 's appreciation ! my whole drive of focusing all my work on improving techniques of preparation for em has come from wanting to take better pictures and get more of that appreciation .", "sharing , mutual appreciation , communion that has been the whole name of the game for me in my research career ." ] ]

[ [ "the purpose of this study was to investigate the association of sdf-1and nf-b expression with clinicopathological parameters of cervical cancer and to evaluate the prognostic value of sdf-1and nf-b expression in cervical cancer patients .", ", we used tissue microarray and the immunohistochemistry method to detect the expression of sdf-1and nf-b in 105 cases of human cervical cancer tissues and their paired adjacent tissues .", "however , to the best of our knowledge , the final role of sdf-1and nf-b in cervical cancer remains unclear . in the present study", "in women , cervical cancer is the second most common malignant tumor worldwide and is one of the leading causes of cancer - related death in developing countries .", "human papillomavirus ( hpv ) is considered the major cause of cervical cancer , but viral infection alone is not sufficient for its development .", "therefore , it is important to better understand molecular events in the invasion and metastasis of cervical cancer and to develop novel prognostic markers and therapeutic strategies ." ], [ "a standard immunohistochemistry method was used to study sdf-1and nf-b expression in cervical cancer tissues and the adjacent tissues .", "we analyzed a total of 105 formalin - fixed , paraffin - embedded cervical cancer tissues and the adjacent tissues at the time of operation from january 2002 to november 2013 at east hospital , tongji university .", "the expression of sdf-1 and nf-b in cervical cancer and adjacent cancer tissues was compared with the paired wilcoxon test .", "important related clinicopathological parameters of the patients , such as age , tumor size , figo stage , lymphatic metastasis , stromal invasion , differentiation , and survival time , were obtained from each patient s medical records and are shown in tables 1 and 2 .", "chi - square test and fisher s exact test were used to assess the association between clinical characteristics of cervical cancer patients and sdf-1and nf-b expression .", "the prognosis of cervical cancer and sdf-1and nf-b expression were determined using kaplan - meier survival analysis and log - rank test for univariate analysis ." ], [ "we analyzed a total of 105 formalin - fixed , paraffin - embedded cervical cancer tissues and the adjacent tissues at the time of operation from january 2002 to november 2013 at east hospital , tongji university .", "the survival time was calculated from the date of surgery to the date of death , or the last known follow - up .", "important related clinicopathological parameters of the patients , such as age , tumor size , figo stage , lymphatic metastasis , stromal invasion , differentiation , and survival time , were obtained from each patient s medical records and are shown in tables 1 and 2 .", "all these cancer tissues were confirmed as cervical cancer by medical examination and hematoxylin and eosin staining after surgical resection .", "none of the patients received adjuvant chemotherapy , radiation therapy , or other anti - tumor therapies .", "all cervical cancer tissue samples included in this investigation were obtained with patients written informed consent ." ], [ "a standard immunohistochemistry method was used to study sdf-1and nf-b expression in cervical cancer tissues and the adjacent tissues . briefly , the tumor tissues and adjacent tissues were fixed in 10% formaldehyde and embedded in paraffin and then we cut the paraffin sections into 4-m sections .", "results are presented as the percentage of the staining cells ( 0 to 100% ) in tissues .", "staining under 20% of the tissue cells or no staining was included in the negative group ( ) , while the others belonged to the positive group ( + ) .", "all the sections were assessed under an optical microscope by 2 independent investigators , and any discrepancy in immunohistochemistry was resolved by consensus .", "afterwards , we washed the sections with phosphate - buffered saline ( pbs ) and developed them with 3 , 3-diaminobenzidine ( dab ) for 5 min and counterstained them with hematoxylin .", "we washed the sections with buffer solution for 5 min and then added the primary antibody into them at 4c overnight ." ], [ "the expression of sdf-1 and nf-b in cervical cancer and adjacent cancer tissues was compared with the paired wilcoxon test . chi - square test and fisher s exact test were used to assess the association between clinical characteristics of cervical cancer patients and sdf-1and nf-b expression .", "the prognosis of cervical cancer and sdf-1and nf-b expression were determined using kaplan - meier survival analysis and log - rank test for univariate analysis ." ], [ "therefore , the results demonstrate that higher sdf-1 and nf-b expression in cervical cancer tissues is positively correlated with tumor metastasis and cancer progression , suggesting that sdf-1and nf-b play important roles in the progression . to further evaluate the relationship between sdf-1and nf-b expression and prognosis of cervical cancer , we performed log - rank survival analysis according to the sdf-1 and nf-b expression level and patient survival data .", "furthermore , a multivariate cox regression analysis demonstrated that sdf-1 expression and lymph node metastasis are independent predictors of the os in cervical cancer patients .", "the survival analysis demonstrates that the cervical survival rate of the patients with negative sdf-1 and nf-b expression is significantly better than that of the patients with positive ones ( p<0.05 , figures 3 , 4 ) .", "the relationship between patients clinical parameters and the expression of sdf-1and nf-b is shown in tables 1 and 2 , respectively , showing that the expression of sdf-1 in the cervical cancer tissues is significantly correlated with tumor size ( =10.794 , p=0.001 ) and figo histology grade ( =7.000 , p=0.008 ) . however , there was no statistical correlation between sdf-1 expression and patient age , lymph node metastasis ( lnm ) status , stromal invasion , or tumor differentiation ( p>0.05 ) .", "typical immunohistochemistry images of sdf-1 and nf-b in cervical cancer tissues and paired adjacent non - tumor tissues are shown in figures 1 and 2 .", "the positive percentage of sdf-1 expression in cervical cancer and adjacent non - tumor tissues were 68.6% ( 72/105 ) and 8.6% ( 9/105 ) , respectively . the positive percentage of nf-b expression in cervical cancer and adjacent non - tumor tissues were 60.0% ( 63/105 ) and 5.7% ( 6/105 ) , respectively .", "the chi - square test was used to confirmed that the difference in the expression level of sdf-1and nf-b between cervical cancer tissues and paired adjacent non - tumor tissues was statistically significant ( p<0.05 ) ." ], [ "the positive percentage of sdf-1 expression in cervical cancer and adjacent non - tumor tissues were 68.6% ( 72/105 ) and 8.6% ( 9/105 ) , respectively . the positive percentage of nf-b expression in cervical cancer and adjacent non - tumor tissues were 60.0% ( 63/105 ) and 5.7% ( 6/105 ) , respectively .", "typical immunohistochemistry images of sdf-1 and nf-b in cervical cancer tissues and paired adjacent non - tumor tissues are shown in figures 1 and 2 .", "the chi - square test was used to confirmed that the difference in the expression level of sdf-1and nf-b between cervical cancer tissues and paired adjacent non - tumor tissues was statistically significant ( p<0.05 ) ." ], [ "the relationship between patients clinical parameters and the expression of sdf-1and nf-b is shown in tables 1 and 2 , respectively , showing that the expression of sdf-1 in the cervical cancer tissues is significantly correlated with tumor size ( =10.794 , p=0.001 ) and figo histology grade ( =7.000 , p=0.008 ) .", "therefore , the results demonstrate that higher sdf-1 and nf-b expression in cervical cancer tissues is positively correlated with tumor metastasis and cancer progression , suggesting that sdf-1and nf-b play important roles in the progression .", "however , there was no statistical correlation between sdf-1 expression and patient age , lymph node metastasis ( lnm ) status , stromal invasion , or tumor differentiation ( p>0.05 ) .", "similarly , the expression of nf-b in the cervical cancer tissues was significantly correlated with tumor size ( =7.421 , p=0.006 ) , figo histology grade ( =10.182 , p=0.001 ) , and lymph node metastasis ( lnm ) status ( =4.762 , p=0.029 ) .", "however , there was no statistical correlation was found between nf-b expression with patient age and stromal invasion and tumor differentiation ( p>0.05 ) ." ], [ "to further evaluate the relationship between sdf-1and nf-b expression and prognosis of cervical cancer , we performed log - rank survival analysis according to the sdf-1 and nf-b expression level and patient survival data .", "the survival analysis demonstrates that the cervical survival rate of the patients with negative sdf-1 and nf-b expression is significantly better than that of the patients with positive ones ( p<0.05 , figures 3 , 4 ) .", "furthermore , a multivariate cox regression analysis demonstrated that sdf-1 expression and lymph node metastasis are independent predictors of the os in cervical cancer patients ." ], [ "the expression of sdf-1 was positively correlated with the expression of nf-b ( r=0.201 , p=0.040 ; table 3 ) ." ], [ "many studies have revealed that the over - expression of sdf-1 is found in various malignancies , including lung cancer , prostate cancer , breast cancer , and pancreatic cancer .", "the results of this study indicate that the expression of sdf-1 is increased in cervical cancer tissues and is correrated with tumor size and figo histology grade .", "we found that the expression of nf-b is increased in cervical cancer tissues and is correrated with tumor size , figo histology grade , and lymph node metastasis .", "the sdf-1/crcr4-nf-b pathway participates in the regulation of cell prliferation , apoptosis , and angiogenesis in cervical cancer .", "the increased expression of vegf and mmps caused by sdf-1-cxcr4 interaction and many nf-b - related biological macular - involved cell cycle , apoptosis , and chronic inflammation responses may mediate the initiation and progression of cervical cancer [ 3032 ] .", "substantial evidence indicates that sdf-1 can mediate the activation of sdf-1/crcr4-pi3-mark - nf-b pathway , pi3k / akt , wnt , and erk pathways , and further promotes the invasion and progression of cancers [ 1719 ] ." ], [ "results of our study indicate that the expression of sdf-1 is significantly associated with tumor size and figo histology grade .", "the expression of nf-b is significantly associated with tumor size , figo histology grade , and lymph node metastasis .", "we also found that positive sdf-1 or nf-b expression is significantly correlated with poor prognosis ." ] ]

[ [ "oral manifestations include obtuse gonial angle , grooved palate , anterior cross - bite , malpositioned teeth associated with increased incidence of dental caries and periodontitis , hypoplastic maxilla , receded chin , delayed eruption of permanent teeth , delayed exfoliation of deciduous teeth and hypoplasia of root - obliterated pulp spaces .", "pycnodysostosis was first reported in 1923 by montanari , and he called it as atypical achondroplasia .", "the main characteristics are short stature , cranial dysplasia , increased bone density and fragility ." ], [ "a 47-year - old man reported to the department with a complaint of deformed lower jaw for the past 10 years .", "orthopantomograph revealed generalized bone loss , multiple missing teeth and obtuse gonial angle with loss of bone structure on the left side of the mandible involving the body and ramus [ figure 9 ] .", "subsequently , there was frequent exfoliation of teeth with fracture at different sites in the lower jaw ." ], [ "the patient presents with characteristic facies , dwarfism , beaked nose , prominent head and generalized increase in the density of bones not sufficient to obliterate medullary canals or cranial orifices .", "intraoral clinical presentation included altered pattern of exfoliation of deciduous teeth and eruption of the permanent dentition .", "our patient showed evidence of sequestrum in relation to the tooth 46 as a result of osteomyelitis ." ], [ "as pycnodysostosis is associated with inappropriate bone remodeling , it can pose a challenge for a dental health care professional to provide treatment as there can be serious complications , such as osteomyelitis arising as a result of dental infections .", "now - a - days , symptomatic treatment is provided for patients with pycnodysostosis , with the main intention of prevention of fractures .", "tooth extractions in these patients demand certain special care , such as carrying out the surgery atraumatically with proper asepsis . oral hygiene practices and frequent visits to" ] ]

[ [ "metals considered herein are antimony ( sb ) , arsenic ( as ) , cadmium ( cd ) , lead ( pb ) , mercury ( hg ) , silver ( ag ) , and uranium ( u ) .", "we offer a brief summary of the ways in which the c. elegans model has shed novel insights on the various mechanisms of metal detoxification .", "the particular metals considered in this review , antimony , arsenic , cadmium , manganese , mercury , silver , and uranium , are among the classes of essential nutrients , as is the case with copper and manganese , as well as the nonessential , naturally occurring metals , such as arsenic , cadmium , and mercury , all of which can induce toxicity depending on the concentration level and exposure duration . over time", "recently , the role of c. elegans as a biomonitor in environmental risk assessment has also been explored [ 2528 ] . ", "the accumulation of metals in the environment , stemming from their origination in the earth 's crust , as well as from anthropogenic sources , creates the potential for significant human exposures and subsequent health hazards ." ], [ "furthermore , the mt - pcs-1 triple mutant was found to display an additive sensitivity toward cadmium .", "gsh levels were found to be increased in worms subjected to acute exposure , whereas worms subjected to chronic exposure exhibited depleted levels of gsh . in their hormetic model , helmcke and aschner demonstrated an increase in gst-4::gfp expression after low concentration , acute exposure , a finding which indicates that gst-4 may be involved in the hormetic response to mehg . taken together , the data from these studies suggest that gst-4 contributes to the response to mehg exposure , but that knockdown of this gene does not affect with overall lethality . in a study examining the role of pcs in the elimination of cadmium , vatamaniuk and colleagues reported that the c. elegans pcs-1 gene encodes a functional pc synthase critical for heavy metal tolerance . using double stranded rnai against pcs-1 , this group showed that , although the progeny of worms injected with the dsrnai and exposed to cadmium ( 525 m ) managed to reach adulthood , these worms were small , necrotic , sterile , and had a much shorter lifespan than did the wild - type controls . after being exposed to 50 and 100 m concentrations of cadmium , the pcs-1 worms arrested at the l2l4 stage were necrotic and died by day 6 .", "the results were definitively dependent on the presence of cadmium , because pcs-1-deficient worms , in the absence of cadmium exposure , responded identically to the wild - type controls . ", "results confirmed that oxidative stress plays a role in arsenic - induced toxicity by mutating glutamylcysteine synthetase ( gcs ) ( gcs-1 ) , the rate - limiting enzyme in gsh synthesis , in worms .", "glutathione peroxidase ( gpx ) catalyzes the oxidation of gsh to gssg in the presence of ros ( figure 1 ) ." ], [ "mts bind both metals of physiological importance such as copper and zinc , as well as xenobiotics including arsenic , cadmium , mercury , and silver .", "metallothioneins ( mts ) belong to a family of cysteine - rich low - molecular - weight metal - binding proteins ( mw 3,50014,000 da ) involved in metal detoxification and homeostasis .", "the protective roles of mts can be ascribed to their three primary functions : ( 1 ) metal homeostasis , ( 2 ) heavy metal detoxification , and ( 3 ) protection from oxidative stress . additionally , these proteins have been identified as contributors to the hormetic response [ 39 , 61 ] . ", "understanding the factors that modulate mt expression will allow for the improved understanding of metalloid toxicity and will provide more effective therapeutic approaches to metalloid - based chemotherapy .", "indeed , mts have been associated with a protective effect in cells under numerous states of disease and stress . ", "binding of metals by mts may be transient , as mts are capable of rapidly releasing metal ions ." ], [ "bacterial arsa atpase is the catalytic component of an oxyanion pump that is responsible for resistance to arsenite and antimonite . in this study ,", "the role of multidrug resistance - associated protein ( mrp ) in arsenite and cadmium toxicity was explored in a study by broeks and colleagues .", "tseng and colleagues investigated the arsa protein - mediated detoxification of the metalloids , as(iii ) and sb(iii ) .", "au and colleagues studied the divalent - metal transporter ( dmt1 ) following exposure to manganese .", "in addition , the rnai knockdown of tir-1 , an upstream component of the p38 mapk pathway in the pgp-5 transgenic reporter strain , was shown to significantly reduce pgp-5 induction following exposure to cadmium ." ], [ "further , exposure to cadmium ( 1 ppm ) induced a detectable production of -galactosidase without inhibiting feeding behavior .", "results showed that cadmium inhibited feeding behavior significantly but not completely , as a minimal rate of feeding continued at high cadmium concentrations .", "mercury also was shown to inhibit feeding at concentrations similar to those necessary for the induction of a stress response ; however , the difference in this instance was less than two fold .", "the hsp16 family of stress proteins is produced in c. elegans only under stress conditions [ 8082 ] . in a study examining the effects of mehg exposure , hsp-4::gfp was measured immediately following the treatment of l1 worms for 30 minutes and l4 worms for 15 hours with this toxicant . after 30 minutes of acute exposure to mehg ,", "the stress response was induced at a concentration of cadmium that was ten times lower than the lc50 .", "jones and candido exposed nematodes to cadmium or mercury and measured feeding behavior . for these studies , transgenic lines containing the promoter sequence for hsp16 genes which regulate the production of e. coli-galactosidase were used . accordingly , to measure stress , levels of this protein were assessed ." ], [ "the c. elegans model system will be critical for these investigations , as knockouts are easily generated and provide a wealth of information about metal detoxification in a genetically retractable , inexpensive , and in vivo model .", "future studies are necessary in order to enhance our understanding of the complex interplay of multiple - cell detoxification systems in response to exposure to different metals .", "the selectivity and sensitivity of each of these proteins is highlighted in the large body of accumulated research on different metal toxicities as well as various systems of metal detoxification .", "the use of c. elegans as an experimental model has produced considerable insight and valuable information regarding the multiple and varied processes of metal detoxification .", "however , the overall mechanisms , temporal activation , and interplay between different cell detoxification systems remain elusive .", "conclusive biochemical evidence has indicated that different metals are not handled in the same capacity ." ] ]

[ [ ". therefore , we investigated whether the lep gene g2548a polymorphism and lepr gene 668a / g ( q223r ) polymorphism might be involved in the pathogenesis of obesity .", "has been reported as a major risk factor for individuals . with the increasing prevalence of obesity , studies on candidate genes for obesity", "obesity is a complex heterogeneous disease that is caused by genes , environmental factors , and the interaction between the two .", "obesity is also a multifactorial condition , and many endocrine and inflammatory pathways are involved in its development and in obesity - related diseases .", "obesity results from the combined effects of genes , lifestyle , and the interactions of these factors , and both familial and nonfamilial factors play an important role in its development . a genetic predisposition to obesity", "the lipostat system , mediated by leptin and its hypothalamic receptor , reduces food intake and increases thermogenesis [ 10 , 12 ] . the leptin ( lep ) and leptin receptor ( lepr ) genes have been evaluated for polymorphisms that could potentially be related to the pathophysiology of obesity and its complications . although the polymorphisms in these genes have been evaluated [ 1315 ] , the association of these polymorphisms with obesity is still controversial", "most obesity - predisposing genes encode the molecular components of physiological systems related to energy balance ." ], [ "this study included 127 obesity patients ( 93 women , 34 men ) and 105 controls ( 62 women , 43 men ) provided from the department of internal medicine , gazi osmanpaa university in tokat , turkey .", "lep g2548a and lepr 668a / g polymorphisms were analyzed by polymerase chain reaction based restriction fragment length polymorphism ( pcr - based rflp ) methods . the pcr protocol consisted of an initial melting step of 2 ", "the frequencies of the alleles and genotypes ( hardy - weinberg equilibrium ) in patients and controls were compared with analysis , and 95% confidence intervals were calculated .", "all patients received a complete clinical evaluation , and all individuals in the control group were healthy and were selected by excluding the diagnosis of obesity .", "min at 94c , followed by 35 cycles of 30 s at 94c , 30 s at 55c ( for lep ) , 30 s at 60c ( for lepr ) , and 30 s at 72c , and a final elongation step of 5 min at 72c .", "genomic dna was isolated from white blood cells by a kit procedure ( invitrogen life technologies , carlsbad , ca , usa ) and stored at 20c ." ], [ "the lep / lepr gg / gg combined genotype was found to increase the risk of obesity compared to the controls ( p < 0.05 ) ( table 4 ) . in the combined genotype analysis based on the mean bmi of obesity patients", "patients and controls were genotyped for both the g2548a polymorphism in the lep gene promoter and the 668a / g polymorphism in the lepr gene .", "we found no statistically significant difference in the genotype frequencies of the lep gene polymorphism in patients and control groups ( p > 0.05 ) .", ", there was no association of the lep / lepr combined genotype and obesity between patients with a bmi 35 kg / m and patients with a bmi near 30 kg / m ( p > 0.05 ) ( table 4 ) .", "allele frequencies in the lepr gene showed no statistically significant association ( p > 0.05 ) ( table 3 ) . the lepr gene a allele was 61.4% in patients and 69.5% in the control group , while the g allele frequency was 38.5% in patients and 30.4% in the control group . in the combined analysis of the lep and lepr genes ," ], [ ", we analyzed the frequencies of lep g2548a and lepr 668a / g polymorphisms in obesity patients in a turkish population .", "our findings indicate that the lep g2548a polymorphism is not a relevant obesity marker and that the lepr 668a / g polymorphism may be related to obesity in a turkish population . additionally , the lep / lepr gg / gg combined genotype was found to increase the risk of obesity in patients compared to controls", "there was no statistically significant difference between the groups with respect to the lep genotype distribution ( p > 0.05 ) and allele frequencies ( p > 0.05 ) .", "our results showed a statistically significant difference between groups with respect to the distribution of the lep / lepr gg / gg combined genotype .", "obesity results from both gene - gene and gene - environment interactions , and in our study we examined the gene - gene interactions of the lep / lepr genes and their link to obesity ." ] ]

[ [ "susceptibility weighted imaging ( swi ) is a relatively new magnetic resonance ( mr ) technique that provides innovative sources of contrast enhancement visualising the changes in magnetic susceptibility that are caused by different substances like iron , haemorrhage or calcium .", "latest advances have allowed the technique to be refined , thereby expanding its clinical applicability to brain imaging as a complementary source of information to conventional t1-weighted and t2-weighted imaging sequences .", "the basic concept of this technique is maintaining phase information into the final image , discarding phase artefacts and keeping just the local phase of interest .", "thus , deoxyhaemoglobin can behave like a contrast agent with long tes for differentiating arteries from small veins , which can be as small as 100200 m and therefore difficult to detect with conventional mr angiography techniques , such as time of flight ( tof ) or phase contrast ( pc ) ." ], [ "at our institution , mr imaging ( mri ) is performed by using a 1.5-t system ( magnetom avanto ; siemens , erlangen , germany ) with a 12-channel head coil .", "the swi sequences are reconstructed with the minimum intensity projection algorithm ( minip ) and multiplanar reformation ( mpr ) techniques to obtain images with thickness ( 310 mm ) and position comparable to those of conventional sequences . the minip algorithm has the characteristic to enhance the visualisation of veins while attenuating the signal from the brain tissue ( fig . 1 ) . \n", "swi has been investigated at 3 t with excellent results , especially concerning brain tumours and detection of cerebral microbleeds [ 6 , 7 ] ." ], [ "sporadic cerebral amyloid angiopathy ( caa ) is a common small - vessel disease associated with ageing , dementia and alzheimer s disease , that can only be diagnosed histopathologically following biopsy or at post - mortem examination .", "swi has been proposed in the evaluation of clinical response to anti - angiogenetic drugs and in the differential diagnosis with pseudo - progression after chemo- and radiotherapy .", "this technique has been proved to be useful for the assessment of tissue viability in patients with hyperacute cerebral ischaemia , as it provides functional information about the ischaemic penumbra . in acute arterial stroke ,", "a correlation with mr pwi has also been attempted . however , larger comparative studies of pwi and swi are still needed to determine a more precise role of the new techniques in the grading of cerebral neoplasms .", "it consists of deposition of amyloid protein within the small and medium - sized cerebral arteries , which is likely responsible for increased vessel fragility and it is one of the major causes of lobar intraparenchymal haemorrhages in the elderly .", "swi plays a substantial role in the identification and characterisation of cerebral vascular malformations , first of all improving their detection rate . on the other hand , allowing simultaneous visualisation of the different compartments of cerebral avms and of the relationship with one another and with the brain parenchyma , it is particularly valuable for therapeutic planning ." ], [ "hypertensive encephalopathy and especially posterior reversible encephalopathy syndrome ( pres ) , when the signal abnormalities of the white matter are more symmetrical and located in parieto - occipital regions , should be taken into consideration for differential diagnosis .", "sporadic cerebral amyloid angiopathy ( caa ) is a common small - vessel disease associated with ageing , dementia and alzheimer s disease , that can only be diagnosed histopathologically following biopsy or at post - mortem examination .", "computed tomography ( ct ) and conventional mr techniques are usually unable to show cerebral microbleeds ( cmbs ) , which can be frequently observed on t2 * -weighted gradient - echo mri and have a typical lobar distribution .", "it consists of deposition of amyloid protein within the small and medium - sized cerebral arteries , which is likely responsible for increased vessel fragility and it is one of the major causes of lobar intraparenchymal haemorrhages in the elderly ." ], [ "histologically they represent focal accumulations of haemosiderin - containing macrophages in the perivascular space of small brain vessels , indicating previous extravasation of blood , and are often associated with the presence of a symptomatic haemorrhage in the corresponding area . the number of cmbs , which remain detectable for years , is significantly associated with bp levels . moreover , the presence of deep cmbs can be a useful marker of bp - related small vessels disease , helping in the differential diagnosis with caa . \n", "hypertensive encephalopathy is characterised by multiple cmbs which are usually silent and can be discovered when the patient is investigated with mri in order to understand the cause of an intraparenchymal haemorrhage located outside the basal ganglia .", "they can be recognised bilaterally in the basal ganglia and in the subcortical temporal white matter ( arrows )", "cmbs are usually discovered both in deep basal ganglia and subcortical white matter ( fig . " ], [ "the ability to measure the amount of ferritin in the brain can be used for a better understanding of the progression of the disease and is also helpful in predicting the treatment outcome .", ", there is evidence of increased iron in the substantia nigra , swi sequences can be proposed as a useful imaging tool to identify iron deposition as a biomarker for disease progression , although longitudinal studies are required to support the usefulness of this specific application .", "accurate localisation of the subthalamic nucleus can also be achieved in the swi phase maps at 3 t , allowing safe direct targeting for placement of electrodes in the treatment of parkinson s disease . in 7098% of patients with alzheimer s disease ,", "iron deposition increases in the brain as a function of age , primarily in the form of ferritin and particularly in oligodendrocytes , but also in neurons and microglia .", "abnormally elevated iron levels are evident in many neurodegenerative disorders , including parkinson s disease , alzheimer s disease , huntington s disease and amyotrophic lateral sclerosis ." ], [ "the visualisation of draining veins within areas of impaired perfusion allows the identification of penumbral brain tissue in a different way from the current perfusion - weighted imaging ( pwi ) techniques ( fig . 5 ) . \n", "this technique has been proved to be useful for the assessment of tissue viability in patients with hyperacute cerebral ischaemia , as it provides functional information about the ischaemic penumbra . in acute arterial stroke ,", "the evaluation of the intravascular content of deoxyhaemoglobin in hypoperfused brain is one of the most interesting applications of swi .", "swi is also capable of identifying the acute intravascular clot in the main and distal branches of the cerebral arteries ." ], [ "swi is also capable of identifying the thrombosed pial vein , which is responsible for the development of oedema into the white matter , due to its high sensitivity in the demonstration of an intravascular clot .", "swi has become a functional method for evaluating cerebral venous sinus thrombosis ( cvst ) by demonstrating engorgement of the venous system as a result of venous hypertension and collateral slow flow .", "dural sinus thrombosis causes an increase in deoxyhaemoglobin concentration in the veins involved that appears as a prominent area of hypointense signal intensity on swi ; if cvst is treated successfully , this effect will disappear ." ], [ "cerebral arteriovenous malformations ( avms ) are easily displayed by conventional mri and mr angiography because of their characteristic high flow , whereas venous malformations such as cavernomas , developmental venous anomalies and capillary telangiectasias can not be adequately visualised without contrast medium administration and ge sequences , as they mainly consist of slow - flow small vessels .", "swi plays a substantial role in the identification and characterisation of cerebral vascular malformations , first of all improving their detection rate . on the other hand , allowing simultaneous visualisation of the different compartments of cerebral avms and of the relationship with one another and with the brain parenchyma , it is particularly valuable for therapeutic planning .", "for the evaluation of high - flow vascular malformations ( i.e. avms and dural arteriovenous fistulas ) the use of both minip and mip post - processing techniques can improve the image quality .", "the elevated diagnostic accuracy of swi compared with digital subtraction angiography ( dsa ) has been recently reported for the detection of arteriovenous shunting ( avs ) in brain avms . \n" ], [ "haemorrhagic dai lesions on swi can be six - times better detected than t2 * -weighted conventional ge sequences and the recognisable volume of haemorrhage is approximately twofold greater ( fig . ", "reformatted swi images in the sagittal plane are particularly helpful in the assessment of corpus callosum haemorrhages . both number and volume of haemorrhagic lesions correlate with neuropsychological deficits . \n fig . 13diffuse axonal injury in a 14-year - old boy who had severe tbi following a motorcycle crash .", "a flair image identifies multiple hyperintense lesions in the splenium of the corpus callosum and in frontal subcortical and periventricular white matter ." ], [ "swi has been proposed in the evaluation of clinical response to anti - angiogenetic drugs and in the differential diagnosis with pseudo - progression after chemo- and radiotherapy .", "a correlation with mr pwi has also been attempted . however , larger comparative studies of pwi and swi are still needed to determine a more precise role of the new techniques in the grading of cerebral neoplasms .", "kim et al . recently assessed the added value provided by swi in the differential diagnosis of solitary enhancing brain lesions compared with the use of conventional mri alone .", "ce - swi has been found to be equivalent or even superior to ce - t1 images in the evaluation of most tumours with necrotic areas ( figs . " ], [ "swi , which is a combination of ge techniques with phase information , represents a useful tool for the identification and characterisation of vascular malformations and for a better understanding of cerebrovascular diseases . despite some inherent limitations", ", swi has increasing indications for neuroradiology and should be included in the routine imaging protocols of trauma and vascular abnormalities .", "further investigation is still needed into its extensive clinical application in neurodegenerative diseases and tumoural pathological conditions ." ] ]

[ [ "shallots ( wild garlic / osghordion ) with the scientific name of allium hertifolium , is one of the most famous plants from the alliaceae family . for a long time , shallots have been used as a source of food and medicine in iran .", "this study was conducted to compare shallots in the traditional and modern medicine in order to make a better use of this precious plant .", "the active ingredients of the plant could be referred to agapentagenin , allicin , omega-3 , omega-6 , and minerals such as potassium , sodium , magnesium , iron , copper , zinc , and manganese ." ], [ "subsequently , the findings were reviewed , classified , and reported in a tabular format .", "to collect appropriate data , resources and articles in trustworthy databases ( e.g. cochrane library , pubmed , google scholar ) and traditional literature ( e.g. makhzan - ul - adwiah , canon , zakhireh - ye khwarazmshahi ) were studied ." ], [ "shallots are rich in fatty acids and minerals with many pharmacological effects such as its effect on the respiratory and nervous system and blood dilution , as reflected in the modern medicine", ". however , certain effects as mentioned in traditional medicine ( e.g. anti - warts , anti - lipoma , anti - kidney stone , and its diuretic effects ) are not covered in research studies of the modern medicine ." ], [ "some of these effects have been investigated in modern medicine ; however , further evaluation of its safety and dosages for clinical use is necessary .", "depending on its natural habitats , shallots have different pharmacological effects for which many usages are mentioned in traditional medicine .", "furthermore , some cases have not been studied in modern medicine , which could be the basis for future research ." ] ]

[ [ "the objective of this paper is to review the current literature and to discuss evidence on clinical , paraclinical , magnetic resonance imaging ( mri ) , and cerebrospinal fluid ( csf ) markers as predictors of disability progression in ms .", "multiple sclerosis ( ms ) is a chronic idiopathic disorder of the central nervous system ( cns ) sustained by a multifocal inflammatory process predominantly affecting myelin - sheathed axons .", "although traditionally viewed as a white matter ( wm ) demyelinating disorder , ms is characterized by acute and chronic axonal and neuronal loss , as shown for long by pathological and neuroimaging studies [ 1 , 2 ] .", "given that ms is mostly diagnosed in subjects in the third and fourth decade of life , the availability of reliable predictors of long - term prognosis is extremely important . ", "acute inflammation causes the development of plaques , characterized by blood - brain barrier ( bbb ) breakdown , perivascular cellular infiltration , demyelination , and axonal degeneration ." ], [ "the typical clinical course of ms is relapsing - remitting ( rr ) , characterized by an initial event of acute or subacute neurological disturbance , generally indicated as clinically isolated syndrome ( cis ) followed by recurrence of symptoms over time .", "cis is the type of onset in around 85% of ms cases , while the remaining 15% of patients have a progressive disease from onset ( primary progressive ( pp ) ms ) .", "in addition , it has been shown that the progressive phase of ms is an age- rather than a disease duration - dependent process , since age at pp and sp ms onset overlaps significantly in large observational studies and subsequent disability progresses along a common age - driven trajectory independent of onset epoch and previous clinical course . in this perspective , older age at onset may be viewed as a favourable prognostic factor , meaning a longer disease - free interval before ms symptoms occurrence in life and an older age at which significant disability milestones are reached , compared to early onset", "conversely , ciss generally recover well and may remain monophasic for a long time interval before conversion to clinically definite ms occurs . since cis represents the earlier clinical manifestation of rr ms , this patient population is of great value for identification of predictive and prognostic disease markers compared to definite ms cases who are necessarily in a more advanced stage .", "indeed , edss , which is the most largely used disability scale in ms clinical practice , is clearly unbalanced towards ambulation impairment .", "progressive onset is an unfavourable prognostic predictor per se , since motor , sphincter control , and cognitive impairment are prominent features of the clinical picture , neurological disability continues to worsen over time , and no effective treatment exists ." ], [ "all together these studies confirmed that neurological and neuropsychological disability in ms are likely the consequence of both visible and invisible wm and gm damage .", "the strength of correlation between gm tissue loss and progression of disability exceeds that related to wm lesions or atrophy ( table 2 ) .", "however , while it may seem obvious that patients who develop new wm lesions are worse off than those without new lesions , conventional mri has been shown to have a prognostic value only in patients at disease onset : high t2-weighted lesion load in patients with a cis has been associated with an increased risk of subsequent conversion to clinically definite ms and long - term disability accumulation [ 101 , 102 ] . by contrast , in a more advanced phase of the disease , the strength of relationship between conventional mri measures and subsequent disability progression is rather weak [ 33 , 34 ] . in a recent study including 548 placebo - treated rr ms patients , the multivariate analysis indicated just edss score and t2 lesion load as factors independently predicting the clinical progression", "unfortunately , gm damage is poorly evaluated by conventional mri and to achieve more accurate estimates of such a damage it requires multiparametric mri approach including unconventional and quantitative mri techniques , many of which are not yet available or practicable in routine diagnostics .", "given its increased availability and its sensitivity in detecting ms lesions , conventional mri has become the main imaging tool in the ms diagnostic work up as well as in monitoring treatment response to disease - modifying drugs ." ], [ "the examination of csf represents a valuable procedure in investigating a number of inflammatory and degenerative neurological disorders .", "in addition to the classical biochemical and electrophoretic approaches , the proteome complexity of csf can be tackled today by a number of methods , hence , indicating that scientists involved in this frontier are fishing in the right pond . however , in a disorder with a complex pathogenesis , such as ms , individual biomarkers , taken singly , are likely to reflect only isolated components of ongoing neuroinflammation and neurodegeneration , hence , lacking prognostic significance . moreover , most of the investigated ms biomarkers , while of invaluable diagnostic help , are currently unsuitable for predicting disease progression . according to their biological role ,", "several csf markers of inflammation have been investigated for potential prognostic value in cis and early ms patients .", "csf tau concentration in ms patients with both relapsing and progressive forms of the disease has been reported to be higher compared to controls in several studies [ 110 , 115119 ] , although other researchers did not replicate this finding [ 120122 ] ." ], [ "research will need to focus on large longitudinal observational studies and clinical trials exploring the correlation of unconventional mri measures and selected csf proteins with the development of irreversible neurological disability .", "which is not straightforward in all cases , clinicians have to be prepared for the challenge of prognostic predictions in order to give adequate responses to patients concern about their future life with ms . among the determinants of ms burden ,", "therefore , prognostic markers of long - term disability progression are strongly needed in ms .", "on the other hand , research on csf biomarkers has gathered convincing preliminary evidence only for nfh and nfl as predictors of disability progression .", "development of irreversible neurological disability , particularly when affecting motor and cognitive functions , has the highest impact on patients quality of life and health system costs ." ] ]

[ [ "the excitability of the rectified model neuron was initially tested with the original model data obtained from the neuron modeldb corresponding to the model of a cortical pyramidal cell by hu et al .", "the current to the center of the n - th compartment of the model neuron consists of the following components : capacitive current , ion currents across the membrane and ohmic currents to the left and right neighbors .", "this model incorporates tapering diameters , uneven channel distribution within compartments of one type as well as a reduced membrane capacity of 0.02 f / cm in order to simulate myelination .", "we assumed a monopolar spherical electrode in an infinite homogeneous extracellular medium with a resistivity of e=300 cm . under quasi - static conditions" ], [ "in contrast to experimental recording , computer simulation allows snapshots of membrane voltages as functions of neuron 's length coordinate ( fig .", "according to the activating function concept ( rattay , 1986 , 1999 ) the slopes of membrane voltage at the beginning of the stimulus pulse reflect the first response of the applied electric field and these slopes are proportional to fictive current pulses injected individually in each of the compartments .", "starting at rest , first compartment responses are proportional to the activating function which is independent of the ion channel composition ( rattay , 1986 , 1999 ) .", "( 1)the distal end of the axonal initial segment with high nav1.6 channel density is very sensitive to cathodic stimulation and this is the site of spike initiation in many cases.(2)however , the neuron is even more excitable at the third and fourth node of ranvier , in spite of essentially lower ion channel densities .", "the distal end of the axonal initial segment with high nav1.6 channel density is very sensitive to cathodic stimulation and this is the site of spike initiation in many cases .", "4f ) . note that this rather small difference in activating function minima favors nodal excitation in spite of half nodal nav1.6 channel densities when compared to the other activating function side lobe in the unmyelinated axon . increasing the cathodic stimulus of the subthreshold case of fig .", "the decrease in the maximum sodium conductance gnav1.6 ( from 320 to 160 ms / cm ) for compartments of type nr compared to those of type ais , the firing threshold is further reduced by 5% to 7.7 a and cathodic block threshold appears again at 24 a . above the center of the second internode ( xelectrode=518 m , zelectrode=27.6 m ) threshold current increases for propagating spikes to 21.8 a and blockade threshold to 45 a . when the electrode is shifted in constant distance along the axis of the neuron , several phenomena" ], [ "the aim of the study was to study the effects of external low current stimulation on a cortical model neuron with respect to changing microelectrode position and configuration . in order to enlighten the neural elements which are activated ,", "nonetheless we observed an alternative activation of the cell when the electrode is placed in the vicinity of the dendrites . shortening the electrode - fiber distance allows indirect spike generation in the ais ( fig .", "the electrode has been shifted in the axial direction , showing a varying , non - uniform excitation pattern along the neural axis . a model based on recently reported nav1.2 and nav1.6 channel distribution ( hu et al . , 2009 ) has been used to calculate thresholds for different pulses and varying distances to the electrode by radial offset . during simulations we identified the spike initiation sites with special emphasis on spikes generated in the dendrite by direct stimulation .", "starting at the resting state , we have demonstrated that regular dendritic spikes need an excited region of minimum size to obtain enough intracellular current for the neighboring segments to reach threshold . in case of external point source stimulation" ] ]

[ [ "peptide- and protein- hydration is the dominant factor in the stabilization of spatial molecular structure , in the process of protein folding by gating hydrophobic residues , and in the mechanisms of peptide and protein mediated reactions [ 14 ] .", "we present here , for the first time in the international literature , a comparative investigation of literature d , c , n , and o nmr and crystallographic data in order to provide a coherent hydration model of amino acids and selected derivatives at different ionization states in aqueous solution and in the crystal state .", "investigation of the structural and functional role of water molecules , bound to proteins and peptides , requires a sufficient understanding of the hydration process of their building blocks [ 1 , 2 ] .", "the hydration of amino acids and their derivatives at a molecular level , therefore , is of great importance and has been extensively studied with x - ray crystallography [ 1 , 3 ] and a variety of spectroscopic techniques including multinuclear magnetic resonance spectroscopy [ 2 , 813 ] , ir and raman spectroscopy [ 1416 ] , icr mass spectrometry , and laser ablation in combination with microwave spectroscopy .", "water molecules , therefore , can be considered as an integral component of biomolecular systems with dynamic , functional , and structural roles [ 47 ] ." ], [ "crystal structure databases provide a rich source of information to extract details on the architectures and interactions of molecules .", "the concept of five- and six - membered conjugated rings , along with three - center ( bifurcated ) and 4-center ( trifurcated ) hydrogen bonds , has been acknowledged and accepted widely as an important factor in determining the structure and function of molecules ranging from inorganic to organic and biological molecules [ 1 , 3539 ] .", "this kind of search provides the opportunity to examine the formation of intramolecular and intermolecular hydrogen bond in small molecule crystal structures [ 33 , 34 ] .", "furthermore , port and pullman studied theoretically the formate ion - water interaction as a prototype of the carboxylate group .", "three energetically favourable hydration sites were obtained , two equivalent sites on the carboxylate oxygens at the exterior of the ion and one water bridging the two oxygen atoms ." ], [ "computational methods complement the experimental results by providing information on the microscope and physicochemical details on the interplay between water and the biomolecule of interest [ 4447 ] . for example , introduction of solvent effects into molecular dynamics can provide an atomic description of the folding and unfolding of a protein .", "furthermore , there is an array of theoretical approaches that have been utilized for treating nmr shieldings in solution , that can be classified as continuum models [ 49 , 50 ] and molecular dynamics simulations .", "\n o shielding changes of amino acids as a function of molar fraction of dmso / h2o , the decrease in the longitudinal relaxation times ( t1 ) of c d and c , and the increase in line widths of n and o at acidic ph relative to those at neutral ph may be interpreted with the hypothesis that the cationic form of amino acids is more hydrated by 1 to 3 molecules of water than the zwitterionic form .", "constructively , the tentative models illustrated in figure 8 should be further validated by in silico and experimental approaches ." ] ]

[ [ "selective rie and buffered oxide etching through these multilayer stacks ( diluted pi / trilayers of inorganic materials / trilayers of inorganic materials / diluted pi ) formed mesh structures that enabled release of active layers from the temporary substrate by dissolving the pmma layer in acetone .", "photolithography and buffered oxide etching created vertical interconnect access ( via ) holes for electrical connections between layers .", "another trilayer of sio2 ( ~300 nm)/si3n4 ( ~400 nm)/sio2 ( ~300 nm ) served as encapsulation , with openings at the locations of the sensing electrodes and peripheral contact pads for interfacing to an external daq system .", "releasing , retrieving and transferring the doped si nms onto a temporary substrate , consisting of si wafer with a bilayer coating of pi / pmma , followed procedures similar to those described for passive electrode arrays .", "patterning a mesh structure across the multilayer ( i.e. pi , sio2 , pi and pmma ) by rie followed by immersion in buffered oxide etchant exposed the base layer of pmma to allow its dissolution in acetone .", "photolithography and lift off in acetone defined a patterned layer of mo ( sputter deposited , thickness ~300 nm ) for the gate electrodes and metal interconnects .", "# smi-22r , covance , princeton , nj ) , and anti - ionized calcium binding adapter molecule 1 ( iba-1 , 1:1000 , cat ." ], [ "transfer onto a film of plga ( ~30 m thick ) , facilitated by heating to temperatures close to the glass transition of the plga ( 55~60 c , lactide / glycolide ratio of 75:25 composition ) , followed by elimination of the top layer of pi by rie completed the fabrication .", "patterning a mesh structure across the multilayer ( i.e. pi , sio2 , pi and pmma ) by rie followed by immersion in buffered oxide etchant exposed the base layer of pmma to allow its dissolution in acetone .", "retrieval onto a slab of pdms enabled removal of the bottom exposed layer of pi by rie .", "bonding an acf cable to the terminal regions of the si nm interconnects yielded connection points for interfaces to external data acquisition ( daq ) systems .", "spin casting and patterning a top coating of pi ( ~300 nm thick ) placed the si nm electrodes and interconnects near the neutral mechanical plane .", "plasma enhanced chemical vapor deposition ( pecvd ) formed a layer of sio2 ( thickness 100 nm ) as encapsulation . patterned etching with buffered oxide etchant removed the sio2 from the electrode regions .", "photolithography and reactive ion etching ( rie ) defined a pattern of electrodes and interconnects in the si nms .", "fabrication of the passive electrode arrays began with solid state phosphorus doping ( ph-1000n source , saint gobain , usa , 1000 c for 10 minutes ) of p - type device si on a si on insulator ( soi , top si ~300 nm , soitec , france ) wafer . removing the buried oxide layer of the soi by wet etching with concentrated hf released the device si as a si nm , retrieved with a slab of the elastomer poly(dimethylsiloxane ) ( pdms ) and transfer - printed to a spin - cast bilayer of poly(methylmethacrylate ) ( pmma , ~800 nm thick ) and polyimide ( pi , ~300 nm thick ) on a si wafer ." ], [ "selective rie and buffered oxide etching through these multilayer stacks ( diluted pi / trilayers of inorganic materials / trilayers of inorganic materials / diluted pi ) formed mesh structures that enabled release of active layers from the temporary substrate by dissolving the pmma layer in acetone .", "photolithography and buffered oxide etching created vertical interconnect access ( via ) holes for electrical connections between layers .", "another trilayer of sio2 ( ~300 nm)/si3n4 ( ~400 nm)/sio2 ( ~300 nm ) served as encapsulation , with openings at the locations of the sensing electrodes and peripheral contact pads for interfacing to an external daq system .", "transfer printing steps followed , according to procedures similar to those for the passive electrode fabrication .", "releasing , retrieving and transferring the doped si nms onto a temporary substrate , consisting of si wafer with a bilayer coating of pi / pmma , followed procedures similar to those described for passive electrode arrays .", "deposition of a trilayer of sio2 ( ~300 nm)/si3n4 ( ~400 nm)/sio2 ( ~300 nm ) by pecvd formed the interlayer dielectric ." ], [ "a craniotomy exposed a 48 mm region of cortex in either left or tight or in both hemispheres .", "all recordings were taken in reference to a distant stainless steel bone screw inserted through the skull during the surgery . a commercial stainless steel microwire electrode ( ~100 um stainless steel wire from california fine wire ) placed at 0.5 mm depth from the cortical surface in close proximity to the bioresorbable electrodes served as a control during acute recordings .", "2 is representative of four different acute experiments , each of which lasted 5 - 6 hours .", "the procedures , which were approved by the institutional care and use committee of the university of pennsylvania , involved an anaesthetized rat with its head fixed in a stereotaxic apparatus .", "the animal was anesthetized with initially ketamine / xylazine and then isoflurane throughout the craniotomy and neural recordings .", "neural data was acquired by a fhc multi - channel neural amplifier ( fhc inc , bowdoin , me , usa ) and an acquisition system ( 16 bit axon instruments digidata 1322a , axon instruments , foster city , ca ) ." ], [ "brief electrical currents ( ~250 - 600 a , 1 ms / phase , biphasic pulse ) were passed between the electrodes to activate the intrinsic muscles of the vibrissae , causing a visible protraction of the whiskers .", "a pair of needle stimulating electrode were inserted into the left mystacial pad at various locations .", "current amplitude and electrode spacing was adjusted for focal activation , usually 1 - 4 whiskers .", "a skull screw was placed in the left frontal bone to serve as the reference electrode for the recordings .", "one 150-g , sprague - dawley rat was anesthetized with a ketamine ( 60 mg / kg ) , dexdomitor ( 0.25 mg / kg ) solution and placed in a stereotaxic frame .", "the following procedures were approved by the institutional care and use committee of the university of pennsylvania ." ], [ "a screw electrode was placed contralaterally to the experimental array , with another such electrode placed posterior to lambda as a ground and reference .", "the electrode was placed on the exposed dura and a slurry of gel foam and saline was layered on top of the electrode .", "eeg signals were collected continuously from 3 channels on the array and from the screw .", "after 1 week the animal was placed in a cage for video / eeg recording .", "the rat was given meloxicam for postoperative pain and allowed to recover on a heating pad .", "the skull and electrodes were then covered with dental cement and the connecting plug was secured on top ." ], [ "# smi-22r , covance , princeton , nj ) , and anti - ionized calcium binding adapter molecule 1 ( iba-1 , 1:1000 , cat .", "# a-21141 , and alexa fluor 568 goat anti - rabbit igg , 1:1000 , cat .", "# bm-220 , boston bioproducts , ashland , ma ) , followed by 4% paraformaldehyde ( pfa , cat .", "# gs-0500 , equitech - bio inc . , kerrville , tx ) for one hour at room temperature ( rt ) and then incubated overnight at 4 c with the following primary antibodies : anti- glial fibrillary acidic protein ( gfap , 1:1000 , cat .", "# a-11011 , invitrogen by life technologies , grand island , ny ) . after the final washes ( 3 20 min in pbs )", "after 320-minute washes in pbs , sections were incubated with the corresponding fluorescent secondary antibodies ( alexa fluor 488 goat anti - mouse igg2b , 1:1000 , cat .", "control sections were incubated with omission of one or both primary antibodies , adding only the secondary antibodies to exclude false - positive labeling .", "serial sections , spanning the entire craniotomy site , were mounted on charged slides and stored at 20c until use . for immunostaining ," ], [] ]

[ [ "the aim is to explore how home care workers coordinate their daily work , identify coordination issues in situ and discuss possible actions for supporting seamless and integrated elderly care at home .", "integrated care is a common concern for health and social care systems throughout the world .", "this definition suggests that there is a need for both inter- and intra - organisational cooperation since multiple organisations and professionals must cooperate and coordinate their services in order to provide care to an individual . when discussing integrated care , elderly care is often in focus [ 25 ] .", "the definition that is used in this study describes integrated care as the .co - ordinated set of services which are planned , managed and delivered to individual service users across a range of organisations and by a range of co - operating professionals and informal carers [ 2 , p. 14 ] .", "the challenges concerning the complicated elderly care situation involve demographic changes , elderly with multiple care demands and the endeavour to accommodate the care needs of elderly at home for as long as possible [ 6 , 7 ] .", "what is more , the trend towards deinstitutionalisation in combination with the move towards advanced palliative care , which previously was provided by the hospital , into the patients home , increases the number of home care interventions [ 810 ] .", "in addition , information technology ( it ) is often suggested as a way to improve cooperation and coordination and support integrated care [ 10 , 15 , 16 ] ." ], [ "for example , cscw has highlighted the importance of supporting awareness ( awareness is here understood as the way in which cooperative actors make sense of and act upon their joint endeavours ) . in addition , it has been shown that human actions are both situated and flexible according to the social and physical conditions that are in place . as a response to the latter finding , cooperative work is most often explored through workplace studies in situ .", "the concept of cooperation has a long history within the fields of social sciences and sociology . in recent years", "cscw research has highlighted several important aspects of the nature and requirements of cooperative work .", ", cooperation has also been a focus within the field of computer supported cooperative work ( cscw ) .", "the main endeavour with cscw research is to understand the nature and requirements of cooperative work with the objective of designing computer - based technologies for cooperative work arrangement [ 19 , p. 5 ] . while some of this research focuses on the first part of the cscw acronym , other centres focus mainly on the social aspect in different kinds of cooperative work arrangements [ 21 , 22 ] .", "furthermore , in this work , the analysis of the cooperative work focuses on the coordination activities that take place in order to provide integrated care .", "these workplace studies often use an ethnographic approach that focus on the work , actions , interactions and technologies typical of complex organizational settings ." ], [ "the group discussions focused on four themes : problematic issues concerning the inter - organisational division of labour and the division of responsibility between home help service and home health care , problematic issues concerning work activities , problematic issues concerning cooperative activities and , finally , general issues concerning information needs and tools .", "for this paper , two coordination activities are identified as particularly important for providing integrated care : planning the process and coordination during home care . the work , actions , interactions and relevant technology used in these two activities are described in the result section .", "the present study was carried out in an inter - organisational home care setting in a county in southern sweden during 20022004 . at the studied county , home health care", "the aim when analysing data was to identify and categorise common themes , activities and/or issues which can explain how cooperative work and coordination is accomplished in the examined work domain .", "the study was part of a broader project with the general aim to support the cooperative work in home care with mobile it tools .", "the actual methods used to collect data may vary in ethnographic studies . in the present study , data were gathered through observational studies , interviews and group discussions . to gain a general overview of the work domain ,", "field notes were taken and transcribed the day after the observations . in order to obtain a more comprehensive understanding of the views and perceptions of the home care workers , group discussions were conducted ." ], [ "coordination of the home care process can be divided into two main activities ; planning the process and coordination during home care . in this paper , these two activities are considered as crucial when providing integrated elderly care at home . the first activity is the starting point for the cooperation between all parties involved while the second describes how the home care workers share information and communicate their efforts during the home care process . during the observations", ", the empirical findings clearly show that the tools used for information and communication do not fully support coordination during the home care process , thus forcing care workers to make additional coordination efforts .", ", the care providers and the care receiver with relatives discuss the home care process .", "svop is an acronym for coordinated health care and care planning ( in swedish : samordnad vrd- och omsorgs planering ) .", ", some interesting situations occurred , which in the group discussions with the care workers were found relevant when improving cooperation and coordination in this setting ." ], [ "in order to deliver integrated elderly care at home , the municipalities and the county councils are required to follow the requirements from the national board of health and welfare .", "one of these requirements concerns information sharing between care providers while the other deals with cooperative care planning before discharge from hospital .", ", the care providers and the care receiver with relatives discuss the home care process .", "therefore , when an individual is scheduled to receive care at home after hospital discharge , a care plan meeting with all parties involved is mandatory . during this meeting", "however , the care workers also stated that sometimes the unit chiefs or care administrators bend the rules in the best interest of the care receiver and sometimes both the home help service and home health care workers actually conduct care interventions beyond those agreed upon during the care plan meeting ." ], [ "the binder is placed in the care receiver s home and consists of several documents and material which provide the care workers with information for administering home care interventions , for supporting involved individuals in daily work situations and for facilitating communication between the care workers involved .", "svop is an acronym for coordinated health care and care planning ( in swedish : samordnad vrd- och omsorgs planering ) .", ", the empirical findings clearly show that the tools used for information and communication do not fully support coordination during the home care process , thus forcing care workers to make additional coordination efforts .", "the home help service groups from all shifts store information about the care receiver and the approved care interventions separately in non - digital form ." ], [ "the most crucial issue here is , who should assume responsibility for care interventions defined as self - treatment by home health care .", "coordinating home care interventions where home care is divided between two organisations is not a straightforward process .", "the present study has identified the planning activity , specifically during the care plan meeting , as a particularly problematic subject .", "bend the boundaries regarding the issue of self - treatment in the best interest of the care receiver . with this in mind , care workers have invented additional tools and routines to support cooperation and coordination in the workplace .", "another possible solution for improving the quality of home care that has been discussed is the merger of the home help service and home health care into one organisation . in 2004 ,", "this shows that it is difficult to demarcate between treatments considered as health care interventions and treatments that are considered as possible for the patient himself / herself to conduct ." ], [ "the most crucial issue here is , who should assume responsibility for care interventions defined as self - treatment by home health care .", "this shows that it is difficult to demarcate between treatments considered as health care interventions and treatments that are considered as possible for the patient himself / herself to conduct .", "coordinating home care interventions where home care is divided between two organisations is not a straightforward process .", "the present study has identified the planning activity , specifically during the care plan meeting , as a particularly problematic subject .", "another possible solution for improving the quality of home care that has been discussed is the merger of the home help service and home health care into one organisation . in 2004 ," ], [ "the second issue considers the care workers need to coordinate their efforts not only between organisations , but also within their own organisation across space and between work shifts .", ", the binder supports the core aim of the cooperation and coordination between home care workers , which is the care of the care receiver .", "additionally , the empirical findings also show that home help service workers lack the mobile phones necessary for communicating effectively with other care providers . providing home help service workers with mobile phones ,", ", the most direct way of facilitating information and communication between care workers may be the introduction of it tools that improve information access and asynchronous communication .", "unfortunately , the present study suggests , like , that the svop binder fails to fully serve the need for effective dissemination of information and coordination during the home care process .", "however , the empirical findings show that the information in the binder is equally important for the intra - organisational coordination taking place between dayshift and nightshift . in this light", "thus , coordination during the home care process is clearly not only an organisational matter , but primarily a technical challenge . from this perspective" ], [ "bend the boundaries regarding the issue of self - treatment in the best interest of the care receiver . with this in mind , care workers have invented additional tools and routines to support cooperation and coordination in the workplace .", "the core aim in the studied setting is to provide the care receiver with good - quality care , and the actors must coordinate their efforts regardless of their organisational belonging to achieve this aim .", "this further emphasises the findings of , which show that the context of elderly care at home involves coordination also with other care providers as well as the inclusion of the care receiver himself / herself and relatives .", "furthermore , the present study also stresses the fact that new care providers might visit the care receiver at home in the future .", "the ethnographic workplace study was conducted in order to understand how coordination is carried out in the daily work , to identify coordination issues in situ and possible actions that may be taken to improve coordination in the studied setting ." ], [ "two important issues of the studied home care setting must be addressed to support seamless and integrated care : the division of care interventions that are defined as self - treatment and the coordination difficulties that arise from the fact that workers are distributed in time and/or space .", "however , since informing and communicating between time shifts within an organisation was shown to be more difficult than between organisations , this may not help resolve the second issue . a more effective solution to this issue may be the introduction of it tools that support distributed access to information and communication between all care workers involved , regardless of organisational belonging .", "the first issue concerns the fact that care is provided by two organisations and can be resolved through policymaking or through the merger of the home help service and home health care into one organisation .", "cooperative work goes beyond organisational boundaries and integrated care must be developed with this situation in mind , beyond organisational boundaries . in view of this , a core subject for future practice and research is to develop it tools that reach beyond formal organisational boundaries and processes while remaining adaptable in view of future structure changes .", "the findings of this paper thus suggest that integrated care needs to be developed not only between organisations but also within each organisation . in the daily work , cooperation and coordination" ], [ "yves couturier , mss , phd , researcher at the geriatric institute of the sherbrooke university and at the research centre for research in youth , science teaching and learning , department of social services , university of sherbrooke , sherbrooke , canada alison petch , dr . director research in practice for adults , blacklers , dartington hall trust , totnes , uk isabella scandurra , phd , medical informatics , chief science officer , apri | ehealth , sjlevad , sweden and maria hgglund , phd , medical informatics , karolinska institutet , health informatics centre , stockholm , sweden" ] ]

[ [ "\n aspergillus species are ascomycetes that are classified in the form subdivision deuteromycotina , as many of them do not show a sexual reproductive phase .", "generally , they are common ubiquitous saprophytes in soil and on dead organic substrates . being classic opportunistic pathogens , invasive infections by aspergillus species almost exclusively develop in immunocompromised patients , while localized infections and allergic bronchopulmonary aspergillosis occur in individuals without immunosuppression . generally , the species aspergillus fumigatus represents the most common inducer of invasive and allergic manifestations , followed by a. terreus , a. flavus , and a. niger [ 1 , 2 ] .", "the fatality of ia is high and depends on the degree of immunosuppression and on the affected organs . without treatment , the mortality is nearly 100% , while under treatment the overall case - fatality rate is nearby 60% and rises to more than 90% in cases of cns aspergillosis [ 1 , 6 , 26 ] .", "the most important path of aspergillus infections is via inhalation of the conidia into the respiratory tract .", "furthermore , ia is the most expensive opportunistic infection in immunosuppressed patients , with annual treating costs in europe of approximately 200 million . in -" ], [ "regulatory factors control and modulate its activity , and cellular receptors mediate the interaction between complement factors and immune cells . representing a potent component of the innate host defence and an interface to adaptive immunity", "furthermore , the antimicrobial effector mechanisms of the complement system might also harbour harmful consequences for the affected host . as known from several infectious and noninfectious diseases , chronic or exceeding complement - mediated inflammation", "the potency of complement represents a valuable tool to attack invading pathogens and to defend the host against penetration and dissemination .", "the most outstanding roles are the direct and indirect defence against infections , the stimulation and regulation of b- and t - cell response , and the disposal of debris [ 2731 ] ." ], [ "further evidence for the crucial role of mbl arises from findings in patients with chronic necrotizing pulmonary aspergillosis and mouse models of pulmonary aspergillosis [ 52 , 53 ] ; these facts suggest mbl as a promising molecule for prophylaxis and therapeutical treatment ( see below ) . ", "after seroconversion , anti - aspergillus antibodies in the serum can trigger the start of the classical complement pathway .", "mbl generally seems to be a molecule of high significance for innate defence against a range of pathogens . in several studies", ", it was shown to bind to various sugars on the surfaces of viruses , bacteria , yeasts , fungi , and protozoa [ 4851 ] ." ], [ "the antimicrobial potency of the complement cascade appears to be independent from direct killing via formation of a mac ; presumably , the thick fungal cell wall block the formation of a pore by the c9 polymers and the subsequent lysis of the cells .", "the thesis that complement represents a central tool in antifungal host defence is supported by several findings .", "this conclusion is strongly indicated by the fact that the level of complement deposition on different aspergillus species correlates inversely with their pathogenicity : highly virulent species like a. fumigatus and a. flavus bind less c3 on their surface than nonpathogenic species like a. glaucus or a. nidulans .", "low doses of this soluble complex were shown to bind to the membrane of a range of cell types , thereby triggering various effects like activation , rescue from apoptosis , and secretion of prostaglandins , which are important regulators of the immune response [ 6367 ] ." ], [ "aspergillus has developed a complex repertoire of effector mechanisms for this purpose ( table 1 ) . ", "single or multiple abscess formation is a characteristic feature of aspergillosis , particularly in the central nervous system ( cns ) .", "the potency of aspergillus to cope with the complement system and to undermine its mechanisms for elimination determines how successful the fungus can establish an infection .", "fungal brain abscesses may arise from these sites of localized parenchymal infection . in this case , white blood cells collect in the affected part of the brain , and fibrous tissue forms around this area , creating a mass ." ], [ "thus , the supply of amino acids in the infected host might downmodulate the secretion of the relevant fungal protease that cleaves the complement factors of the host .", "the high morbidity and lethality of invasive aspergillosis strongly demands for an expansion of the current treatment options . the antimycotic therapy might be completed by new approaches aiming to strengthen the host immune response against the fungus .", "appropriate strategies that target the complement system may aim to the following . our own studies about cerebral aspergillosis showed a clear correlation between the complement levels in the csf and the capacity of csf to opsonize fungal hyphae and designate them for phagocytic killing", ". a therapeutic increase of mbl concentrations in invasive aspergillosis might be an appropriate approach , since patients with chronic necrotizing pulmonary aspergillosis show more frequently mbl haplotypes that encode for low levels of the protein than healthy control persons .", "our own results open the possibility to neutralize the fungal protease(s ) that is / are secreted by aspergillus to degrade complement proteins ." ], [ "the multifaceted interactions between complement and aspergillus represent promising approaches for future therapeutic strategies that may help to improve the outcome of invasive aspergillosis .", "they hide from recognition , acquire complement regulatory molecules from the host , and secrete proteases to degrade complement factors . ", "despite new antifungal drugs and improved medical treatment , invasive aspergillosis remains a dangerous threat for immunocompromised patients , as the innate immune defence is the most crucial weapon against this infection .", "the complement system is of particular importance , as it harbours multiple effects against infectious diseases , bridges the elements of the human defence network by a multitude of factors , and helps to preserve the homeostasis of the body .", ". however , highly virulent aspergillus species have evolved mechanisms to evade the attack by complement ." ] ]

[ [ "mitochondria prepared in this way were active for at least \n 56 h , as determined by their ability to maintain a stable transmembrane \n potential in the presence of oxidizable substrates .", "mitochondria ( 0.2 mg / ml protein ) were added to 1.5 ml of the basic \n incubation medium , which contained 125 mm kcl , 5 mm \n mgcl2 , 10 mm tris , 10 mm hepes ( ph adjusted \n to a particular value between 6 and 8 with koh or hcl ) , 10 m \n egta , 5 mm succinate or 5 mm glutamate , and 5 \n mm malate as oxidizable substrates . due to a tendency of \n precipitation at alkaline ph in the presence of inorganic phosphate , \n concentration of mgcl2 was reduced to 0.5 mm .", "the deposit of \n mitochondria was homogenized in isolation buffer ii at a final protein \n concentration of 20 mg / ml and stored on ice until use .", "the fraction containing the mitochondria located between 42 and 24% \n percoll was carefully withdrawn by a syringe and washed from percoll twice by \n pelleting in isolation buffer i. the resulting mitochondrial suspension was \n diluted in isolation medium ii , which was similar to isolation buffer i , \n except for the concentration of edta ( 0.1 mm ) and lack of albumin , \n and spun down at 12,000 g for 10 min .", "mitochondrial \n transmembrane potential ( m ) was estimated \n using fluorescence quenching of the cationic dye safranin o that is \n accumulated and quenched inside energized mitochondria .", "h2o2 generation was \n calibrated by constructing calibration curves using known \n h2o2 concentrations in the standard incubation buffer \n together with amplex red and horseradish peroxidase but without mitochondria \n at all ph values 68 . at acidic ph ,", "hydrogen peroxide hydrogen peroxide was measured using a2 \n m concentration of the fluorescent amplex red dye in the \n presence of 1 unit / ml horseradish peroxidase as previously described \n ( 26 ) .", "the protein \n concentration in the mitochondrial samples was determined using a protein \n assay kit ." ], [ "to study the ph - dependent component in the mechanism of reactive oxygen \n species generation in mitochondria , we used three types of incubation media \n with different impacts on the ph and electrical components of proton motive \n force through the inner membrane : condition 1 , the medium without permeant \n anions , such as pi ; condition 2 , the medium of condition 1 \n supplemented with pi ; condition 3 , the medium of condition 2 \n supplemented with nigericin .", "8 shows that upon \n application of rotenone , regardless of depolarization , the rate of ros \n generation increased with the increase of medium ph .", "in addition to the use of \n pi and nigericin , application of the ionophores fccp and \n valinomycin can be instrumental in manipulating matrix ph to study its role in \n mitochondrial ros generation . both of these ionophores can decrease membrane \n potential ; however , protonophore fccp acidifies the matrix by increasing \n proton leak , whereas valinomycin causes increase of matrix ph by carrying \n k into the matrix , decreasing and , thus , facilitating \n the proton ejection by the electron transport chain . to stress the \n qualitatively different effects of these ionophores", "these data show that our mitochondrial preparations are good in \n coupling between respiration and phosphorylation in physiological range of ph . \n ", "thus , all presented data \n show the same pattern of ros production increase in conjunction with the \n alkalization of medium ." ], [ "here we show that \n mitochondrial matrix ph is one of the factors controlling ros signaling .", "the whole set of experiments presented here supports the proposed \n ph - dependent mechanism of ros generation in mitochondrial respiratory chain \n and its link with mitochondrial permeability transition .", "our results clearly show that even in the absence \n of ph gradient ( figs . \n ", "the activation of ucps can down - regulate the level of ros by controlling the \n current of protons into the matrix without considerable compromise of \n mitochondrial atp production . to demonstrate the phenomenon of ph regulation of ros production by the \n respiratory chain", "effect of medium ph on rate of ros release ( a ) and level of \n membrane potential of mitochondria oxidizing complex i substrates glutamate \n and malate ( b and c ) .", "3a \n ( triangles and circles ) and \n 5 ) , thus indicating that in \n these circumstances the effect of ph dominates over the opposite effect of \n . figure 7.effect of medium ph on rate of ros release ( a ) and level of \n membrane potential of mitochondria oxidizing complex i substrates glutamate \n and malate ( b and c ) .", "this resulted in a substantial \n decrease of ros release , which requires functional integrity of the \n mitochondrial membrane ( figs . \n ", "matrix ph was shown to be an essential factor in \n induction of permeability transition \n ( 38 ) .", "steep inhibition of respiration observed in condition 1 at ph 7.5 and 8 , in \n all likelihood , is the consequence of the loss of cytochrome c in the \n course of permeability transition ." ] ]

[ [ "myositis is an acute , sub - acute , or chronic inflammation of skeletal muscles ." ], [ "arboviral titers for west nile virus was negative and so was the rocky mountain spotted fever titers . on the day 3 of his hospitalization ,", "a previously healthy 12-year - old boy was admitted to driscoll children s hospital in corpus christi , tx , usa , with a 9 day history of fever , and 7 day history of pain and weakness in the lower extremities .", "he was discharged home on doxycycline to complete a 10 day course and prednisone was discontinued .", "three days prior to admission , he was seen by a nurse practitioner and diagnosed with otitis media and pharyngitis .", "a diagnosis of myositis was made and the patient was given analgesics and oral prednisone as dermatomyositis and polymyositis were amongst the differential diagnosis ." ], [ "myositis can be caused by strenuous activity , muscle trauma , illicit drug injections , genetic diseases , connective tissue disorders , diabetes and infections .", "it has been known that murine typhus resolves even without treatment . to our knowledge , this is the first pediatric case reported of murine typhus associated with myositis and paraparesis .", "rhabdomyolysis was considered as one of the top differential diagnosis for our patient and given intravenous fluids ." ], [ "physicians practicing in or near rickettsia typhi - endemic areas need to consider this in the differential diagnosis of children with evidence of myositis .", "making this diagnosis may have a significant impact on the course of the disease because of the availability of antimicrobial therapy against rickettsial organism ." ] ]

[ [ "the various attributes of m comprehensive data and metadata , uniform normalization , access to raw data dumps , a computable structure , versioning of the database and web - based analysis tools facilitate both efficient human interrogation of the dataset and machine - based computational analysis .", "importantly , experimental metadata in m is human curated from each microarray publication converting each chemical and growth attribute into a structured and computable set of experimental features with consistent naming conventions and units . finally , all versions of the database builds are maintained and accessible in perpetuity on the website to facilitate the future interpretation and comparison of results published on m data .", "a set of web - based browsing and analysis tools is provided to facilitate efficient interrogation of the dataset without extensive computational skills .", "moreover , the consistency and uniformity of the dataset facilitates downstream comparison of results and findings based on the dataset ." ], [ "a geo dataset contains a collection of biologically and statistically comparable microarray samples processed using the same platform .", "large microarray depositories like geo and arrayexpress focus on the archiving of expression data as used in specific publications .", "thus , all builds are labeled with a version number that references the underlying mysql schema of the database and a build number that denotes the particular set of microarray data ( e.g. e_coli_v3_build_2 uses mysql schema version 3 and is the second compendium built for e. coli ) .", "figure 1.all of the available e. coli affymetrix antisense2 expression data for the transcription factor lexa and its known target reca were downloaded from ncbi geo profiles ( a ) and from m compendium e_coli_v3_build_1 ( b and c ) .", "all of the available e. coli affymetrix antisense2 expression data for the transcription factor lexa and its known target reca were downloaded from ncbi geo profiles ( a ) and from m compendium e_coli_v3_build_1 ( b and c ) .", "ncbi geo profile data is derived from ncbi geo datasets that contain only a subset of the data in geo , therefore many more samples were available for plotting from m ( 445 ) than from geo ( 85 ) ." ], [ "the experimental condition information underlying each microarray sample is the most under - utilized aspect of compendia collected from multiple disparate sources . in scientific language there are typically multiple units that can be used to describe a particular aspect of an experiment . for example , the amount of glucose added to a media can be described in weight / volume , as a percent solution , or using molarity . to promote large - scale analyses of the relationship between experimental conditions and the expression values of each gene , we provide the quantitative and qualitative features of each experimental condition cataloged in a consistent framework suitable for computation .", "we use human curation to convert the condition metadata in each publication into consistent units and naming conventions , and we use computer validation to provide data integrity ." ], [ "to facilitate large - scale computational analyses of compendium data , we provide bulk downloads of the normalized expression data in m. for each build , we provide separate files containing normalized data for all genes , all genes + intergenic regions , and all genes + intergenic regions + control probes .", "we also provide flat files containing the gene names , probe set names and curated experimental condition information .", "in addition , we provide the raw cel files as a tar archive for researchers interested in using or developing other normalization methods ." ], [ "this page guides the user step - by - step through the process of database selection , experiment selection , gene selection , visualization , analysis and download . at each step ,", "custom datasets constructed on m can be visualized with scatterplots ( a ) , histograms of individual genes ( b ) , heatplots ( c ) , histograms of collections of genes ( d ) and in their genome context using a genome browser ( e ) .", "m currently provides heat plots ( with and without clustering ) , expression histograms ( for individual genes and groups of genes ) , scatter plots and a genome browser for visualization of expression in a genome context ( figure 2 ) ( 13 ) . \n", "all browsing , analytical and download features of m3d are accessed from the same page , the analysis page , on the website .", "figure 2.custom datasets constructed on m can be visualized with scatterplots ( a ) , histograms of individual genes ( b ) , heatplots ( c ) , histograms of collections of genes ( d ) and in their genome context using a genome browser ( e ) .", "for more targeted analysis and data exploration , m allows the flexible construction , visualization and download of custom datasets ." ], [ "the url syntax for this and other plots can be found by clicking the help tab on the main menu of m.", "m provides a simple mechanism for generating links to m genepages , which contain a basic set of plots for each gene .", "for example , strong correlation is often found between the expression of a transcription factor and its targets , a website cataloging known or predicted regulatory interactions might find it useful to provide a scatter plot of the transcription factor 's expression versus its target gene 's expression to allow users to see if expression data currently supports the regulatory interaction .", "in addition all of the plots on m are generated using a simple url syntax so that websites can easily include plots generated by m on their own sites .", "the power of the internet resides in its interconnectivity . biological databases like ncbi ( 14 ) , ecocyc ( 15 ) and regulondb ( 16 )", "provide easy linking mechanisms so that other databases can automatically generate hyperlinks to their content ." ], [ "all of the old and new microarrays are normalized together into a new compendium build . for researchers preferring to submit cel files directly to m , we can generate a template submission to geo , which the researcher can then edit as desired .", "raw cel files are periodically collected from the arrayexpress and geo microarray databases . upon accumulation of approximately 50 new chips for a particular species ," ] ]

[ [ "pharmacists embedded in primary care medical practices , such as those modeled on the patient - centered medical home , are playing increasing roles in interdisciplinary primary healthcare teams.13 however , with limited pharmacist resources and high patient to pharmacist ratios , it is important to identify which patients would benefit most from consultation with a primary care pharmacist .", "we have previously completed a similar assessment of patient requirements for dietician services in primary care.4 while commonly used approaches to identify patients for pharmacist care include physician referrals , drug- or disease - specific programs ( eg , chronic disease management ) , and patients recently discharged from hospital , an alternative strategy is to focus on patients at increased risk of medication - related problems ( mrps).2,57 mrps are events or circumstances involving drug therapy that actually , or potentially , interfere with an optimum outcome for the patient.8,9 several studies have identified factors associated with an increased risk of mrps,1014 and short , self - administered surveys have been developed to help identify patients at risk of mrps.12,15 our objective was to determine the feasibility of using a locally adapted , self - administered , paper - based , patient survey , to identify patients at risk of mrps , in a convenience sample of patients at a single academic family medicine clinic ." ], [ "we conducted a cross - sectional pilot study based on a convenience sample of 100 completed surveys at the university of alberta hospital family medicine clinic in edmonton . at the time of the survey ,", "the two most significant changes made were : 1 ) the focus of question 3 ( present in both surveys ) was changed from high risk medications to a chronic diseases focus , and 2 ) question 9 , does someone else bring any of your medications to your home for you ? was replaced ( as all patients attending the family medicine clinic were ambulatory ) with do you sometimes worry about the long - term effects of your medications ? to determine feasibility , we recorded patient - reported time to complete the questionnaire , and we solicited opinions from the medical office assistants and physicians about the impact of the questionnaire on clinic flow . to estimate the number of patients at high risk for an mrp , we calculated a summary risk score .", "seven family physicians , two family medicine resident doctors , two full time clinic nurses ( one dedicated to chronic disease management ) , and two academic clinical pharmacists ( each working ~0.2 full - time equivalent ) provided service to approximately 7,000 patients .", "all patients registered to be seen by one of the clinic physicians were eligible to participate in this survey , unless they were less than 18 years old , could not read english , or were not responsible for self - management of their medications .", "we used the previously validated , ten - item mrp questionnaire , developed by barenholtz levy , and the modified five - item questionnaire , developed by langford et al , to create an adapted ten - item questionnaire ( figure 1).12,15 to adapt the questionnaire for the primary care ambulatory population , several changes were made .", "responses , after collapsing question 3 into a single yes or no response ." ], [ "we conducted a cross - sectional pilot study based on a convenience sample of 100 completed surveys at the university of alberta hospital family medicine clinic in edmonton . at the time of the survey ,", "seven family physicians , two family medicine resident doctors , two full time clinic nurses ( one dedicated to chronic disease management ) , and two academic clinical pharmacists ( each working ~0.2 full - time equivalent ) provided service to approximately 7,000 patients .", "all patients registered to be seen by one of the clinic physicians were eligible to participate in this survey , unless they were less than 18 years old , could not read english , or were not responsible for self - management of their medications .", "after registration at the reception desk , a medical office assistant asked eligible patients if they would be willing to participate .", "those who expressed interest were given an information letter and a copy of the survey as they were placed in an examination room , and asked to complete the survey while waiting to be seen by their physician .", "the university of alberta health research ethics board ( reb ) approved the study protocol ." ], [ "we used the previously validated , ten - item mrp questionnaire , developed by barenholtz levy , and the modified five - item questionnaire , developed by langford et al , to create an adapted ten - item questionnaire ( figure 1).12,15 to adapt the questionnaire for the primary care ambulatory population , several changes were made .", "the two most significant changes made were : 1 ) the focus of question 3 ( present in both surveys ) was changed from high risk medications to a chronic diseases focus , and 2 ) question 9 , does someone else bring any of your medications to your home for you ? was replaced ( as all patients attending the family medicine clinic were ambulatory ) with do you sometimes worry about the long - term effects of your medications ? " ], [ "to determine feasibility , we recorded patient - reported time to complete the questionnaire , and we solicited opinions from the medical office assistants and physicians about the impact of the questionnaire on clinic flow . to estimate the number of patients at high risk for an mrp , we calculated a summary risk score .", "responses , after collapsing question 3 into a single yes or no response .", "as done by others in the literature , we defined patients who answered yes to three or more questions as being at high risk for a mrp.11,15,16 to allow further comparisons , we did a sensitivity analysis , in which we examined the number of patients who were at risk , while restricting analysis to the five questions developed by langford et al.15" ], [ "forty - three respondents had three or more risk factors identified by the full ten - point questionnaire , and 26 respondents met this criterion in the sensitivity analysis . in view of the limited data , and bearing in mind that this was a pilot study , no further mining of the data was undertaken .", "demographic characteristics , summary risk scores , and time to complete the questionnaire are presented in table 1 . from patient reports in answer to the questionnaire ,", "the questionnaire was not distributed by medical office assistants to consecutive patients , because research was not considered to be a priority in their responsibilities , and clinical tasks sometimes intervened .", "there were no comments from the medical office assistants , or physicians approached during regular staff meetings , to suggest that the questionnaire was intrusive on the clinic s workflow .", "the median time to complete the questionnaire was 2 minutes ( interquartile range : 1.53 minutes ) ." ], [ "the findings of this pilot study suggest that distribution of a mrp questionnaire at the point of care is feasible in a busy family medicine clinic , and that there was a strong signal for potential mrps in the sample studied .", "additionally , we plan to compare the predictive accuracy and feasibility of an automated electronic medical record medication list screening approach for identifying patients at high risk of mrps .", "our results suggest that screening patients at the point of care , using a self - administered mrp questionnaire , was feasible , and that a large proportion of those who complete the questionnaire will have multiple risk factors for mrps .", "our findings support the integration of a pharmacist into family medicine practices , as a member of the patient - centered medical home ." ] ]

[ [ "inflammatory abnormalities and oxidative stress are characteristic findings of obesity and play important roles in the renal damage associated with obesity , which will be discussed in detail in the following .", "although obesity has long been recognized as an independent risk factor for cardiovascular diseases and diabetes mellitus , newer research points to obesity as an important risk factor for chronic kidney diseases ( ckds ) [ 24 ] . in 1974 , weisinger et al . ", "obesity has become a heavy public health problem in the united states , with a prevalence among adults increasing to 32% from 13% between the 1960s and 2004 ." ], [ "thus , mif is a key mediator of the inflammatory and immune response and plays a pathological role in immune - mediated renal injury .", "recent studies have demonstrated that obesity causes chronic low - grade systemic inflammation and thus contributes to the development of systemic metabolic dysfunction that is associated with obesity - related disorders and renal disease [ 2427 ] .", "therefore , hypoadiponectinemia contributes to development of a low - grade systemic chronic inflammation state , suggesting that hypoadiponectinemia may play a causative role in the systemic and vascular inflammation commonly found in obesity and obesity - related disorders , including renal injury , through its proinflammatory effects .", "this suggests that resistin may play an important role in obesity and obesity - associated disease by triggering the release of other proinflammatory cytokines ." ], [ "ros contribute to progressive vascular dysfunction and remodeling through oxidative damage caused by decreased nitric oxide ( no ) bioavailability , impaired endothelium - dependent vasodilatation and endothelial cell growth , apoptosis or anoikis , endothelial cell migration , and activation of adhesion molecules and inflammatory reactions [ 134 , 135 ] .", "oxidative stress is caused by an imbalance between increased production of reactive oxygen species ( ros ) and/or reduced antioxidant activity , leading to oxidative damage to cells or tissue including lipids , proteins and dna .", "physiologically , ros can mediate cellular function , receptor signals , and immune responses on vascular cells . in pathophysiological condition ,", "it is known that oxidative stress is involved in pathological processes of various diseases , such as cancer , diabetes mellitus , hypertension , and cardiovascular disease .", "oxidative stress also plays an important role in the pathogenesis of renal damage through its effects on vascular biology .", "it is also reported that the increase in obesity - associated oxidative stress is due to the presence of excessive adipose tissue accumulation ." ], [ "since adipose tissue mass in obesity contributes to oxidative stress , bariatric surgery - induced weight loss also results in decreasing systemic oxidative stress in adiposity . weight loss induced by diet restriction or bariatric surgery not only improves inflammation state but also reduces oxidative stress state in obesity , which may protect renal function in obesity - related glomerulopathy .", "obesity accelerates the progression of renal injury , associated with augmented inflammation in adipose and kidney tissues .", "diet restriction can prevent or greatly delay the onset of specific degenerative lesions , in particular glomerulonephritis associated with obesity .", "nutritional and surgical interventions are additional approaches to reduce oxidative stress and prevent kidney injury in obesity .", "since ros play a key role in the pathogenesis of renal injury such as glomerulosclerosis and tubulointerstitial fibrosis , approaches to reduce oxidative stress by antioxidants supplementation , nutritional and surgical interventions may have renoprotective effects ." ], [ ". therefore , anti - inflammation and antioxidant interventions may be the potential therapies to prevent and treat obesity - related renal diseases .", "obesity causes chronic low - grade inflammation and systemic and local oxidative stress , which may play a pivotal role in the initiation or progression of obesity - associated glomerulopathy .", "elevated inflammation in obesity is the result of the production of adipokines and increased inflammatory cytokines and decreased anti - inflammatory factors .", "both inflammation and oxidative stress induce damage to renal tubule and glomerulus and result in endothelial dysfunction in the kidney", "oxidative stress is triggered by an imbalance between increased production of ros and/or reduced antioxidant activity ." ] ]

[ [ "5electropolymerization of pyrrole ( a ) and thiophene ( b ) electropolymerization of pyrrole ( a ) and thiophene ( b ) the morphologies of the polypyrrole and polythiophene fibers were investigated using a scanning electron microscope ( leo 1430vp ; carl zeiss smt , oberkochen , germany ) coupled with a backscattered electron ( bse ) detector .", "4chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings polymerization was performed using medical steel wires as working electrodes . an ag / ag electrode was applied as a reference electrode , with platinum net bent into a cylinder as a counterelectrode . for ppy , a potential range from 0.2 to + 2.5 v and seven scans", "the three - electrode cell was filled with electrolyte solution consisting of 100 mm pyrrole / thiophene ( fig . 4 ) and 250 mm tetrabutylammonium perchlorate in acetonitrile.fig . ", "polypyrrole ( ppy ) and polythiophene ( pth ) coatings were synthesized by electropolymerization with a linear sweep voltammetry technique .", "electropolymerization was performed using a homemade electrochemical cell coupled with a high performance potentiostat galvanostat ( pgstat128n series ; metrohm - autolab b.v . ," ], [ "5electropolymerization of pyrrole ( a ) and thiophene ( b ) electropolymerization of pyrrole ( a ) and thiophene ( b )", "4chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings polymerization was performed using medical steel wires as working electrodes . an ag / ag electrode was applied as a reference electrode , with platinum net bent into a cylinder as a counterelectrode . for ppy , a potential range from 0.2 to + 2.5 v and seven scans", "electropolymerization was performed using a homemade electrochemical cell coupled with a high performance potentiostat galvanostat ( pgstat128n series ; metrohm - autolab b.v . ,", "second , an additional 14 scans in the higher potential range from 0.2 to 2.7 v were used ( fig . ", "the three - electrode cell was filled with electrolyte solution consisting of 100 mm pyrrole / thiophene ( fig . 4 ) and 250 mm tetrabutylammonium perchlorate in acetonitrile.fig . ", "polypyrrole ( ppy ) and polythiophene ( pth ) coatings were synthesized by electropolymerization with a linear sweep voltammetry technique ." ], [ "the morphologies of the polypyrrole and polythiophene fibers were investigated using a scanning electron microscope ( leo 1430vp ; carl zeiss smt , oberkochen , germany ) coupled with a backscattered electron ( bse ) detector ." ], [ "the saxs data were recorded within the scattering vector range of 0.15 nm < s < 3.5 nm ( where s = 4sin/ , 2 is the scattering angle , and is the x - ray wavelength ) .", "the sample - to - detector distance was 650 mm , and the exposure time for a single frame was 10,000 s. each sample was measured three times , and the obtained data were averaged .", "the saxs data were corrected for the detector response and normalized to the intensity of the incident beam , and the background scattering ( empty holder ) was subtracted using the saxs_nt v4.1 program package ( bruker axs gmbh , karlsruhe , germany ) .", "small angle x - ray scattering ( saxs ) data were collected using a nanostar system ( bruker axs gmbh , karlsruhe , germany ) with pinhole collimation and a two - dimensional hi star detector with resolution of 1,024 1,024 pixels , mounted on an x - ray tube with a copper anode and equipped with crossed gbel focusing mirrors .", "samples were mounted between two mica windows in sample holders with thickness of 1 or 2 mm ." ] ]

[ [ "thus , the aim of the present study was to determine the vertical distance between the maxillary central incisors and centre of the incisive papilla .", "the maxillary anterior teeth should be positioned as close as possible to the positions originally occupied by natural teeth to achieve a natural appearance in making complete dentures.1 it is necessary to refer to anatomic landmarks to achieve this goal.2 the incisive papilla is a small , pear shaped eminence composed of a pad of fibrous connective tissue overlying bony exit of nasopalatine blood vessels - nerves and one of the significant anatomical landmark in locating maxillary anterior central incisors position in complete denture fabrication procedure ." ], [ "the inclusion criteria were : no restoration and tooth loss on the upper jaw , well - arranged maxillary anterior teeth , no orthodontic treatment , angle class i maxillomandibular relationship , no pathology that affects the dentition or the surface texture and shape of teeth , no incisal wear on the dentition and no gummy smile in the subjects .", "upper jaw impressions were taken on the subjects by using stock impression trays ( teknik dental rostfrei , istanbul , turkey ) and irreversible hydrocolloid impression material ( tulip , cavex holland , haarlem , holland ) . in order to correctly register the incisive papilla and reduce soft tissue distortion", "the centre of the incisive papilla was found measuring the planar distance between the most anterior and posterior borders of the incisive papilla that was on the median line of the palate using a digital caliper which had a precision level at 0.01 mm ( mitutoyo corporation , tokyo , japan ) ( figure 1 ) and halving this distance .", "two mm standard transparent resin plate and a spirit level ( veto , istanbul , turkey ) were used to achieve the parallelism of the described occlusal plane to the base of the stone casts .", "the stone casts were obtained using ada type iii dental stone ( gilidur , fachbereich dental , ludwigshafen , germany ) .", "each stone cast was trimmed following the same procedures to produce a flat base that was parallel to the occlusal plane ( anterior reference point : mesio - labial incisal edge of upper right central incisors ; posterior reference points : mesio - buccal cusp tips of upper first molars ) .", "the flat edge plane of the depth caliper had contacted to the mesial incisal edges of the maxillary central incisors and the midpoint of the flat edge plane of the depth caliper was matched with the midpoint of the maxillary central incisors ( figure 4 ) .", "the midpoints of the incisive papilla were marked on each stone cast ( figure 2 ) .", "the pin of the depth caliper was touched to the midpoint mark of the incisive papilla .", "a digital caliper that was fixed perpendicular to the horizontal bar of a surveyor ( rotaks dent a.s .", "stone casts were mounted to the surveyor by the help of a spirit level to obtain a certain level in the horizontal plane ." ], [ "the kappa scores for the assessment of intra and inter observer agreement were higher than 0.75 which implies substantial agreement between the observers ( tables 1 and 2 ) .", "the mean vertical distance between maxillary central incisors and midpoint of the incisive papilla on the stone casts was 6.700.81 mm ." ], [ "the occlusal plane is a common reference for mounting stone casts and in general , occlusal plane done parallel to the bases of stone cast in standardize manner .", "the vertical relationship between incisive papilla and central incisors can be used in determination of occlusal plane with the reference of other anatomical landmarks together ; however the clinical applicability of this relationship in complete denture construction needs further investigation .", "it is important to orient the stone casts in a standardized manner during measurements so that the results achieved can be applied when artificial teeth are being set in complete denture bases .", "a common average vertical position of the maxillary anterior teeth to the constant landmarks has been found by measuring lots of casts of natural healthy teeth ." ], [ "the dentist and laboratory technician can be use the results of this study as a guideline in fabrication of maxillary occlusal rims and in determination of the position of the occlusal plane with the reference of other anatomical landmarks together .", "this study investigated the vertical distance between maxillary central incisors and centre of incisive papilla .", "however , the wax rim should be modified intraorally to incorporate individual characteristics , and the anterior tooth should be arranged on modified wax rim . also , further investigations are needed in different age , gender , race , dental and skeletal morphology groups ." ] ]

[ [ "here we present new experimental results on the photogeneration \n of singlet oxygen by irradiation of gold nanoparticles with continuous or pulsed laser light , as well as theoretical work pertaining \n to the underlying mechanism(s ) , which so far had not been addressed . \n", "we show that electron temperatures in excess of 2000 c are easily \n achieved in pulsed laser irradiation experiments , whereas cw light \n under similar conditions yields electronic temperatures of at most \n 10 c above room temperature .", "thus , the photogeneration of o2 by gold nps proceeds by different mechanisms \n under different irradiation conditions ; the implications for the further \n development of medical applications of the effect are discussed in \n detail ." ], [ "o2 was \n detected via the bleaching of 1,3-diphenylisobenzofuran ( dpbf ) , \n which is widely used for this purpose .", "irradiation of gold \n nrods in the longitudinal plasmon resonance band at 800 nm was performed \n in the same setup , but using a titanium : sapphire laser ( coherent mira \n 900 ) , aligned on the auxiliary cavity , which prevents mode - locking \n and thus provides continuous - wave laser operation at 800 nm with 1000 \n mw power ; the beam was expanded to 3.4 mm using two lenses . pulsed \n laser irradiation was performed in the same setup , but using the second \n harmonic of a q - switched nd : yag laser ( quantel brilliant ) ( 532 nm , \n 5 ns pulse length , 10 hz repetition rate , 3.5 mm beam size , 15 mj \n pulse energy ) . for experiments that included nps , the absorbance \n of dpbf at 412 \n", "citrate - stabilized spherical \n gold nps with 15 and 46 nm diameter were prepared according to the \n turkevich frens and a seeded growth method , respectively .", "gold nanorods ( nrods ) were synthesized \n using the seeded - growth method reported by dickerson et al . with slight modifications . more details of the \n np preparation are provided in the supporting information .", "functionalization \n with thiolated peg ligands or peptides was achieved by overnight incubation \n with excess ligand , followed by repeated centrifugation for excess \n ligand removal .", "no significant increase of the cuvette temperature beyond a slight \n warming was observed . for most experiments ," ], [ "similarly , a lipid bilayer appears \n to allow oxygen access to the surface of gold nanorods , whereas a dense pentapeptide ( calnn ) capping \n layer on spherical gold nanoparticles is sufficient to suppress the \n photochemical mechanism of cell death .", "it also seems likely that the thick peg capping layer present \n on \n the nanorods used here is the main reason for the absence of o2 photogeneration by nanorods upon irradiation \n in either the transversal or the longitudinal plasmon resonance band \n that was observed here . because of their longitudinal plasmon resonance \n band , which is in the near - ir spectral region with high tissue penetration , \n nanorods are more suitable for practical photodynamic applications \n in tissue .", "the presence of \n gold nps can also lead to increased photogeneration \n of o2 by traditional photodynamic sensitizers , which can be ascribed to the local electric field enhancement in \n the vicinity of metal nps by the plasmon electrons , similar to the \n well - studied sers ( surface - enhanced raman spectroscopy ) effect .", "our results show that irradiation of citrate - stabilized \n spherical gold nps at 532 nm , i.e. , in their surface plasmon band , \n with pulsed or cw laser light leads to the production of o2 , detected here by monitoring the bleaching of dpbf \n absorbance .", "cw irradiation is less efficient \n than pulsed laser \n irradiation in photogenerating o2 since the \n ( equilibrated ) hot electrons , which are the main mediator of the photochemistry \n in the case of pulsed irradiation , do not have sufficient energy / temperature \n to drive o2 photogeneration .", "they show that detectable amounts of o2 are \n generated by irradiation of nps with short laser pulses or cw light \n even in the absence of a photodynamic sensitizer , albeit with low \n quantum yield ." ], [ "singlet oxygen generation by pulsed laser \n irradiation has been shown to act via the equilibrated hot electrons \n that can reach temperatures of several thousand degrees during the \n laser pulse ; cw irradiation , on the other hand , can act only via the \n directly excited primary hot electrons , which rapidly \n lose their energy by electron ", "dpbf has been used successfully to detect \n singlet oxygen that is \n formed when spherical nps are irradiated at 532 nm , either with cw \n or pulsed laser irradiation .", "photodynamic therapy using \n gold nanoparticles will also require careful design of the nanoparticles \n with respect to size , shape , and capping layer and will require internalization \n of the nps , not just attachment to the cell surface , which is sufficient \n for photothermal therapy .", "nevertheless , even cw irradiation can produce enough singlet oxygen \n for photodynamic therapy applications and will allow practical applications \n of the effect at safe irradiation levels .", "electron equilibration , and hence \n is significantly less efficient for the formation of singlet oxygen . \n" ] ]

[ [ "relatively less common complications include crowding , diastema , dilaceration of permanent teeth , cyst formation and eruption into the nasal cavity.6 this case reports presents radiographic features of a unique occurrence of two impacted , inverted mesiodentes in a child patient ; and the 24-month radiographic and clinical follow - up after surgical removal .", "supernumerary teeth are a relatively frequent disorder of odontogenesis characterized by an excess number of teeth , with mesiodens being the most frequent.1 the term of mesiodens is used to refer to an unerupted supernumerary tooth in the midline of maxilla , between the central incisors.2,3 the incidence of mesiodens among caucasians is 0.153% for permanent teeth,4,5 and is found two times more frequently in males , compared to females.46 a mesiodens can manifest bilaterally,46 or in an inverted ( upward ) position.4,5 the frequency of inverted mesiodens constitutes to approximately 967% of all reported cases.711 to date , a total of 278 single inverted mesiodentes have been reported ( table 1 ) . the mesiodens may present a rudimentary morphology with a cone - shaped crown , generally smaller in size than the adjacent normal teeth . it may also be found to mimic a natural tooth shape ." ], [ "an 8-year - old boy was referred to the department of pediatric dentistry with a chief complaint of crowding in the maxillary anterior region .", "apparently , the roots of the permanent central incisors had migrated distally , owing to the presence of the supernumerary teeth .", "panoramic radiograph revealed the presence of two supernumerary teeth , located between the roots of the permanent central incisors ( figure 2 ) .", "the lateral cephalogram showed that the mesiodentes were located buccally to the apices of the central incisors ( figure 4 ) . the treatment plan consisted of surgical removal the inverted mesiodentes .", "removal of the inverted mesiodentes had slightly aided to self - correction of the axial rotations of the central incisors ." ], [ "the timing for surgical removal of the inverted mesiodentes was judged to be suitable , since both maxillary central incisors had totally erupted , showing complete root formation and advanced apical closure .", "although mesiodentes are often located palatally,2 the present case demonstrates the possibility of their occurrence in a more vestibular location .", "the case presented herein was considered to be extremely rare , since inversion of two mesiodentes in a single patient has only been reported once20 ( table 1 ) ." ] ]

[ [ "the new model calls for a greater collaboration across the community , school , and health and education sectors to meet the needs and support the full potential of each child.8 whole school , whole community , whole child ( wscc ) model .", "the whole school , whole community , whole child ( wscc ) model ( figure 1 ) , developed by ascd ( formerly the association for supervision and curriculum development ) and the us centers for disease control ( cdc ) , provides a framework and a call for the health and education sectors to work toward greater alignment and coordination of policy , process , and practice .", "the wscc model , released in 2014 , was developed to ensure that school - community and education - health sector alignments are front and center .", "the benefits of collaboration , alignment , and integration between health and education can best be viewed in 3 key areas : leveraging resources , utilizing resources efficiently , and improving both health and education outcomes .", "the model expands the traditional 8-component coordinated school health ( csh ) approach and deliberately places it inside the larger community in order to emphasize this connection and role .", "this includes not only an increase in the number of school health components from 8 to 10 but also the alignment of an education focus with a health focus .", "their trailblazing efforts demonstrate both the feasibility of implementing the wscc model and the visionary leadership required to do so ." ], [ "we conducted a search of the health and education department 's websites in arkansas , colorado , and kentucky , and the school districts ' websites in maine regional school unit # 22 , and dps for materials demonstrating adoption and implementation of csh and its respective components or the wscc model .", "we also conducted a search of the respective state legislative databases , state health and education department websites , and local school district websites for adopted policy relevant to csh and the wscc model .", "we searched pubmed , web of science , and academic search premier and for relevant peer - reviewed articles around the implementation of aspects of csh or wscc in the 4 states and 2 local school districts .", "in addition , we searched online for news articles and gray literature highlighting the implementation of csh or the wscc model , or aspects of them , in each state and local school district .", "secondarily , we conducted informal reinforcing interviews via phone with 1 person in a key school health leadership role related to the promotion and implementation of the wscc model in each district and state : arkansas , kentucky , and colorado , maine regional school unit # 22 and dps ." ], [ "survey topics include asthma , vision , oral health , nutrition , physical activity , social / emotional health , substance abuse , teen pregnancy , and school culture .", ", an advisory committee is assessing dps ' activities , and will present recommendations for creating a metric to determine future progress in early 2015.36 denver public school is also working on the development of the next generation of their health agenda , dps health agenda 2020 .", "the program review includes a practical living / career studies component , encompassing health education and pe .", "the arkansas legislature adopted act 1220 , landmark legislation addressing multiple areas of a healthy school environment.17 the legislation included requirements for body mass index ( bmi ) screening in schools ; the establishment of a state - level child health advisory committee ( chac ) to develop rules and regulations for school nutrition , physical education ( pe ) , and physical activity , and to make recommendations to the arkansas state board of education and board of health ; and the establishment of a wellness committee in each local school district . act 1220 also created positions for regional community health promotion specialists ( chps ) specifically to assist schools and led to new standards for competitive foods and physical activity in schools , created by the arkansas chac .", ", a school must have a csh committee that is used as a support and resource for collaboration and integration of health education instruction in the school environment ( table 1 ) .", "in arkansas , the state health and education departments have a long history of working collaboratively and with partners to improve the health of students ." ], [ "reports will provide school- and district - level leaders with a more robust picture of the effect their school health efforts have on student performance and classroom behavior , informing the school improvement planning process.31,32 overview of colorado healthy schools smart source * colorado education initiative .", "in arkansas , the state health and education departments have a long history of working collaboratively and with partners to improve the health of students .", ", a school must have a csh committee that is used as a support and resource for collaboration and integration of health education instruction in the school environment ( table 1 ) .", "the program review includes a practical living / career studies component , encompassing health education and pe ." ], [ "in arkansas , the state health and education departments have a long history of working collaboratively and with partners to improve the health of students .", "the 2 agencies have jointly operated the coordinated school health program ( cshp ) for over 2 decades , working together to expand csh in school districts across the state .", "team members provide ongoing support , training , and professional development to school districts throughout the state and to the chps and chns on topics such as wellness policies and administration of the school health index .", "this funding led to the establishment of 22 school - based health centers across the state , providing on - site clinical services for students and connecting them with community partners in an effort to meet their needs better .", "act 180 also provided funding for an annual school - based health center grant , a collaboration among ade , adh , the arkansas department of human services , and medicaid in the schools .", "the arkansas legislature adopted act 1220 , landmark legislation addressing multiple areas of a healthy school environment.17 the legislation included requirements for body mass index ( bmi ) screening in schools ; the establishment of a state - level child health advisory committee ( chac ) to develop rules and regulations for school nutrition , physical education ( pe ) , and physical activity , and to make recommendations to the arkansas state board of education and board of health ; and the establishment of a wellness committee in each local school district . act 1220 also created positions for regional community health promotion specialists ( chps ) specifically to assist schools and led to new standards for competitive foods and physical activity in schools , created by the arkansas chac ." ], [ "kentucky provides another valuable example of a state that has worked to integrate health and education through the alignment of policy at the state level .", "together , staff from each agency have worked together to increase awareness of csh among education leaders across the state , including superintendents , principals , and school board members .", "kentucky 's state health and education departments have enjoyed a strong , collaborative relationship in recent years .", "they have collaborated with state associations including the kentucky association of school councils , kentucky school nutrition association , kentucky family resource youth service centers , and kentucky association of health , physical education , recreation , and dance to promote understanding , adoption , and implementation of csh at the local level .", ", a school must have a csh committee that is used as a support and resource for collaboration and integration of health education instruction in the school environment ( table 1 ) .", "the state agencies have focused on helping education leaders make the connection between the csh components and educational outcomes of academic achievement , discipline , and attendance .", "the state health and education departments worked collaboratively to draft the program review rubric for the practical living / career studies component , setting a high baseline to support and strengthen the integration of health into school - level policies and practices ." ], [ "in colorado , strong collaboration and leadership between health and education partners , both public and private , have been instrumental in advancing the integration of health and education across the state .", "cooperative relationships have been created by aligning the priorities of local foundations with state - level initiatives rather than passing policy .", "in addition to a solid working partnership between the state health and education agencies , the state has benefitted from the strategic support of local foundations and organizations including : the colorado education initiative , rmc health , the colorado health foundation , and kaiser permanente . in 2010", "reports will provide school- and district - level leaders with a more robust picture of the effect their school health efforts have on student performance and classroom behavior , informing the school improvement planning process.31,32 overview of colorado healthy schools smart source * colorado education initiative .", "colorado is working to build on the success of the score card by developing the next phase of a district- and school - level assessment and implementation tool for health policies and practices , called healthy schools smart source ." ], [ "at the local level , many school districts nationally have embraced the importance of addressing the whole child through better alignment and integration of health and education .", "both have benefited from the leadership of superintendents and local school boards that have embraced the importance of educating the whole child .", "denver public school plans to use the results of this survey to improve student health and wellness going forward .", "two districts that provide strong examples of application and implementation of coordinated school health and/or the wscc model include maine regional school unit ( rsu ) # 22 and denver public schools in colorado .", ", an advisory committee is assessing dps ' activities , and will present recommendations for creating a metric to determine future progress in early 2015.36 denver public school is also working on the development of the next generation of their health agenda , dps health agenda 2020 ." ], [ "maine regional school unit # 22 , located in the hampden area , began to intentionally focus on the health and wellness of students and staff in 1991 .", ", it opened a new high school that includes a fitness center , track , and tennis courts open to students , staff , and the community . as a result of these efforts , the wellness council of america awarded the district their gold level workplace wellness award .", "leadership from school board members and the superintendent has been key in rsu # 22 's transformation into a district where health and wellness is a top priority and a value embraced by the school employees and the community .", "the vision to strengthen school health and wellness has been driven by rick lyons , district superintendent since 1992 .", "the wellness team , comprised administrators , faculty , support staff , and community members , has been a key factor behind the district 's school health achievements since its establishment . in 2001 ,", "the district also founded a school health advisory council ( shac ) comprised of administrators , healthcare professionals , and community members .", "it increased the number of positions and staffing time for health education teachers , nurses , and guidance counselors and forged partnerships with behavioral health providers .", "the shac oversees the cshp , which is headed by a school health coordinator employed by the district .", "given rsu # 22 's small size ( approximately 2,200 students and 375 employees ) , the financial commitment to support a full - time school health coordinator speaks to the high priority that school health has in this district . over the last 20 years" ], [ "superintendent leadership also has been critical to the success of dps ' strategic inclusion of student health in the district 's overall priorities and plan . since being appointed to the position by the board of education in 2009 , superintendent tom boasberg has managed the district 's 183 schools , which serve a diverse population of over 90,000 children .", "denver public school has also added a school - based health center every year since 2010 , with a fifth scheduled to open in 2015 . in august 2014 , dps released the current version of its 5-year strategic plan , denver plan 2020 .", "some of the significant accomplishments include dramatically increasing the number of schools that serve breakfast after the bell ; adding pe teachers to elementary schools , which has led to an additional 22 minutes per week of pe classes ; and increasing the number of school counselors , which has corresponded with a decrease in expulsion and suspension rates .", "seventy - two percent of students qualify for free or reduced - price lunch , and 41% speak a language other than english at home.34 the district has also committed significant resources to student health , and made it a part of the district 's strategic planning process . in 2010 , boasberg oversaw the denver school health advisory council 's creation of the dps health agenda 2015 , which outlines the districts ' health priorities.35 the district has since invested over $ 22 million toward its health goals , including the addition of 6 full - time district - funded employees .", "survey topics include asthma , vision , oral health , nutrition , physical activity , social / emotional health , substance abuse , teen pregnancy , and school culture .", ", an advisory committee is assessing dps ' activities , and will present recommendations for creating a metric to determine future progress in early 2015.36 denver public school is also working on the development of the next generation of their health agenda , dps health agenda 2020 .", "denver public school plans to use the results of this survey to improve student health and wellness going forward .", "this version , which was developed with the input of nearly 3,000 educators , parents , students , community partners , and city leaders , includes ", "the district has solicited input from students , parents , and community members through a widely disseminated survey about health issues that most impact students ." ], [ "they also demonstrate the importance of strategic leadership at the state and local level , including support from policymakers , superintendents , local school boards , and community organizations that recognize and seize opportunities to integrate and better align the health and education sectors . moving forward ,", "policymakers need to focus on adoption and implementation of policies and practices that build on the connection between the school health components and educational outcomes , both academic and behavioral . when those in decision - making roles understand and embrace the wscc model , they are able to create programs and policies that lead to collaboration and more effective use of resources , creating healthier school environments that address the needs of the whole child .", "state and local health and education agencies should focus greater attention toward ensuring the adoption and implementation of policies that serve both sectors and students , and promote the formation of collaborative partnerships .", "the wscc model provides a framework for the health and education sectors at the state and local levels to work toward stronger alignment , integration , and collaboration . as lloyd kolbe stated", "they demonstrate that it is possible to prioritize student health within the education system , for the purpose of better addressing the needs of the whole child .", ", the wscc model provides a new opportunity , impetus , and sense of purpose for both sectors : if we prudently could unite the expertise , perspectives , resources , communication , visibility , and political support of national education , health , and related organizations to help schools and colleges implement a wscc approach , we synergistically could increase the impact of each sector , each organization involved ; we could build a lasting national base for new means to improve both education and health ; we could accomplish that which we otherwise cannot.37 whereas the wscc model is new , having been launched in march 2014 , many states and local school districts are already in the process of adapting and adjusting practices and processes to suit the expanded version of csh .", "the 3 states and 2 school districts highlighted all provide strong examples of implementation of various aspects of the wscc model ." ], [ "information contained in this article was not deemed to involve human subjects , and therefore , was considered exempt from institutional review board examination ." ] ]

[ [ "reported here is a case of a trabecular variant of jof in a 17-year - old female patient .", "juvenile ossifying fibroma ( jof ) is an actively growing aggressive lesion containing cells rich in the fibrous stroma containing cellular osteoid , trabeculae of woven bone without osteoblastic lining , with or without clusters of giant cells .", "the suggestive features of the aggressive variant are the presence of the perforation , cortical thinning , tooth displacement , and root resorption ." ], [ "based on clinical , radiographic , advanced imaging studies and histopathological report provided the diagnosis of the trabecular variant of jof affecting left mandible with differential diagnosis of cement - ossifying fibroma , osteoblastoma , and osteogenic sarcoma .", "the lesion was excised by segmental resection using transmandibular approach and reconstruction was done [ figure 7a and b ] .", "a 17-year - old female represented with a chief complaint of pain and slowly progressive swelling of the left side of face along with reduced mouth opening for the last 2 months ." ], [ "both maxilla and mandible are affected with more prevalence for maxilla . in the present case , the duration of swelling noted was 2 months .", "clinically , it is asymptomatic , however rarely it is aggressive and symptomatic . in the present case ,", "the 50% of cases of jof are recorded in multiple sinuses with few occurring in the single sinus .", "the characteristic radiographic features reveal a central opacification with well - defined unilocular to multilocular pattern giving it a ground glass appearance .", "jof mostly strikes children with slightly male predominance with a mean age of 11 years .", "the features like resorption and perforation of cortices , tooth displacement and aggressive growth of the lesion favor the diagnosis as an aggressive variety of jof . in this case , except for tooth resorption all other features like perforation of the cortices and extension into the surrounding tissue was noted ." ], [ "jof is an uncommon clinical entity , because of its aggressiveness and high recurrence rate it is necessary to arrive at an early diagnosis , applying the appropriate clinical , diagnostic approaches , and appropriate treatment for effective results and long - standing follow - up .", "the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )", "has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .", "the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed there are no conflicts of interest ." ], [ "has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .", "the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )", "the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed" ], [], [] ]

[ [ "mr urography ( mru ) can be performed with two different imaging strategies : unenhanced mr urography ( t2w - mru ) , based on heavily t2-weighted fse sequences and contrast - enhanced excretory mr urography ( ce - mru ) , which is performed with a 3d ge t1-weighted sequences following intravenous gadolinium administration .", "the purpose of this prospective study was to compare those two types of mru in terms of ureteral visualization in patients with non - dilated ureters , using diuretic administration by means of a direct confrontation of each technique in the same patient .", ", no recent paper has explored the potential of the repetition of this simple breath hold t2w - mru sequence . our hypothesis was that by using low - dose of furosemide and additional multiple rotations around the ureter may improve the detection of the whole non - dilated ureter as well as mru with intravenous administration of contrast medium and provides a pertinent information .", "low - dose ( 520 mg ) intravenous furosemide administration has been recommended for excretory ce - mru to improve the visualization of the non - dilated upper urinary tract , . to the best of our knowledge", "so that , in routine practice , excretory ce - mru is the technique most commonly used to evaluate the non - dilated collecting system .", "a heavily t2-weighted sequence , utilizing the single - shot fast spin - echo ( ssfse ) sequence , provides static hydrographic images of fluid inside the urinary tract ." ], [ "we have selected 126 patients ( extensive endometriosis : 38 patients , various pelvic carcinoma staging : 54 patients , suspicion for retroperitoneal fibrosis : 15 patients , lymph nodes or retroperitoneal masses recurrency : 19 patients ) with bilateral non - dilated ureter who underwent both a 2d t2w - mru immediately followed by an excretory 3d ce - mru .", "the distension of the ureter on ce - mru was compared with that of obtained on t2w - mru and quoted as higher or equal .", "five minutes later a 2d coronal single shot turbo fast se t2-weighted static fluid mru ( t2w - mru ) was performed localized on the right and the left urinary tract with an acquisition time of 5 s. each sequence was repeated nine times with coronal rotations and cine loop registration on each urinary tract . at the end of this first mru sequence , an intravenous injection of 0.2 ml / kg body weight gadolinium - based contrast medium , ( dotarem , guerbet , roissy cdg , france ) followed by a 15 ml saline", "each patient was explored in addition to our routine protocol for the clinical context with two breath - hold mru sequences in coronal orientation .", "the two types of mru , including original source images and mip reformations available from the workstation , were retrospectively reviewed .", "however all patients were orally informed just before the examination of this additional exploration of their urinary tract regarding to the use of a supplementary drug . during a period of 12 months from april 2012 through april 2013 , among a cohort of 155 patients referred to our mr department for a pelvic with retroperitoneal mr exploration ," ], [ "we have selected 126 patients ( extensive endometriosis : 38 patients , various pelvic carcinoma staging : 54 patients , suspicion for retroperitoneal fibrosis : 15 patients , lymph nodes or retroperitoneal masses recurrency : 19 patients ) with bilateral non - dilated ureter who underwent both a 2d t2w - mru immediately followed by an excretory 3d ce - mru .", "however all patients were orally informed just before the examination of this additional exploration of their urinary tract regarding to the use of a supplementary drug . during a period of 12 months from april 2012 through april 2013 , among a cohort of 155 patients referred to our mr department for a pelvic with retroperitoneal mr exploration ,", "we have excluded from the study the patients with urinary tract dilatation ( n = 6 ) or urinary symptoms ( n = 2 ) , moderate renal deficiency or known allergic reaction to medication ( n = 6 ) and those who had undergone a previous pelvic surgery ( n = 15 ) ( fig .", "this prospective , single - institution study received approval by our local ethical committee and no written informed consent was necessary ." ], [ "the field of view was large enough to cover entirely the retroperitoneum with the exploration of the whole ureter from the uretero pelvic junction to the bladder neck .", "each patient was explored in addition to our routine protocol for the clinical context with two breath - hold mru sequences in coronal orientation .", "five minutes later a 2d coronal single shot turbo fast se t2-weighted static fluid mru ( t2w - mru ) was performed localized on the right and the left urinary tract with an acquisition time of 5 s. each sequence was repeated nine times with coronal rotations and cine loop registration on each urinary tract . at the end of this first mru sequence , an intravenous injection of 0.2 ml / kg body weight gadolinium - based contrast medium , ( dotarem , guerbet , roissy cdg , france ) followed by a 15 ml saline flush was performed .", "mr examinations were performed on a 3.0 t mr unit ( achieva , philips medical systems , best , the netherlands ) by using the phased array dedicated coil for pelvic and lower abdomen exploration .", "five minutes later , coronal excretory phase mr urogram was obtained by means of a 3d breath - hold t1-weighted ge sequence with an acquisition time from 15 to 18 s ( table 1 ) .", "patients were asked to void their bladder before mr examination and received an intravenous antispasmodic medication as glucagon at the dose of 1 mg ( glucagen lab novo nordisk pharmaceutics sa ) at the beginning of the exploration . if no urinary dilatation was observed on the first non - injected routine sequences , the patient received an intravenous injection of furosemide at the dose of 20 mg ( lasilix lab sanofi - aventis ) ( fig .", "patients were orally informed of potential side effects such as increased urination at the end of the exploration ." ], [ "the two types of mru , including original source images and mip reformations available from the workstation , were retrospectively reviewed .", "disagreements were checked by consensus with a third radiologist ( cr ) with twenty years experienced in that field to find a consensus .", "each sequence was evaluated separately and independently by two radiologists ( phh , ga ) with five and three years of experience in abdominal mr imaging , respectively .", "the readings were done in several sessions and in each session ; it was given to each reviewer a random combination of isolated mru with native images and mip .", "readers were neither informed of the clinical context nor the radiological report done by the radiologist who was in charge of the examination ." ], [ "readers evaluated the whole technical image quality with the precise criterion of the presence of disturbing artifacts such as ghosting or pulsation artifacts using a four points subjective scale ( 1 poor , 2 fair , 3 good , 4 excellent ) .", "the distension of the ureter on ce - mru was compared with that of obtained on t2w - mru and quoted as higher or equal .", "the lumbar ureter was divided in two segments : a proximal part ( from the pelvic junction to the level of the lower pole of the kidney ) ( pl ) and a distal part ( from the lower pole of the kidney and iliac crest ) ( dl ) .", "based on visual assessment , readers were asked to score four segments of each ureter .", ", readers were asked to evaluate independently one rotation ( chosen as strictly anteroposterior view ) , 6 rotations and finally the entire sequence ( 9 rotations ) . for ce - mru , they were asked to quote the number of entire ureter identified on mip images .", "the pelvic ureter was also checked with two segments : an upper portion from iliac vessels to mid pelvic cavity ( pp ) and an inferior portion from mid pelvic cavity to the bladder ( dp ) ." ], [ "strength of agreement was classified as poor ( value less than or equal to 0.20 ) , fair ( value between 0.21 and 0.40 ) , moderate ( value between 0.41 and 0.60 ) , substantial ( value between 0.61 and 0.80 ) , or excellent ( value between 0.81 and 1.0 ) .", "the kappa statistic was used to measure the degree of interobserver agreement for qualitative assessment .", "we used the wilcoxon test to compare the scoring of the segmental analysis of our two mru techniques ." ], [ "deviations due to ovarian cysts and follicules were easier to diagnose on t2w - mru than on standard t2 sequence .", "deviation of the pelvic ureter due to the genital tract was found in 118 ureteral segments equally recognized on both sequences ( fig .", "the lumbar distal portion of the ureter was less pertinent for identification on t2w - mru with a sensitivity of 71% vs 78% for ce - mru ( table 2 ) . both segments up and down the pelvic ring have less than excellent identification in both mru techniques by comparison with two others .", "a bilateral entirely opacified ureteral column until the vesicoureteral junction was found in 236/252 cases with ce - mru , simulating a mild obstruction . on the contrary , on one rotation of t2w - mru" ], [ "mru permits an evaluation of the urinary tract without the exposure to ionizing radiation and iodinated contrast medium .", "of course , equally to ce - mru , the major drawback of t2w - mru remains its poor sensitivity in detecting calcifications .", "in addition , t2w - mru has the advantage of obtaining high quality images in a few seconds , without need for multiplanar and mip reconstructions in the contrary of ce - mru . as breath - hold t2w - mru with intravenous diuretic and multiple rotations is sufficient to produce a qualitative study of non - dilated ureter with identification of the peristaltism", "t2w - mru was the first sequence to be proposed to study excretory urinary tract .", "have shown the superiority of enhanced over unenhanced imaging , ce - mru is becoming in clinical routine practice the technique most commonly used to evaluate the non - dilated collecting system . to our knowledge , in the previous recent literature in adult , there are no clinical studies comparing those two mru techniques in the same patient .", "finally , t2w - mru has been shown to be a rapid and non - invasive imaging technique which is useful and reliable to reveal hydronephrosis and perirenal high - intensity signals in acute urinary obstruction , , , ." ], [ "our series was large enough to suggest that pelvic mr imaging combined with t2w - mru allows a complete work - up in a single imaging evaluation , especially if gadolinium injection is not necessary or contraindicated .", "the t2w - mru sequence performed with multiple coronal orientations and diuretic administration is sufficient to identify entirely the non - dilated ureter ." ], [ "the authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome ." ], [ "the authors confirm that any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript ." ] ]

[ [ "the first case was described by cruveilhier in 1835 and termed as hamartoma . till date , less than 200 cases have been described with synonyms of brunner gland adenoma , brunner gland hamartoma ( bgh ) or brunneroma .", ". however , it may present with a variety of clinical presentations depending on location and tumor size such as abdominal pain , dyspepsia , nausea , vomiting , upper gastrointestinal ( gi ) bleeding and occasionally obstructive symptoms with associated chronic pancreatitis . \n", "there is no sex predilection and patients present in the fifth to sixth decades of life .", "they are usually seen as incidental findings on imaging with duodenal bulb as the most common location" ], [ "\n a 42-year - old man presented with history of pain epigastrium since one year and recurrent vomiting within half an hour of taking food since one month .", "microscopy showed a tumor composed of lobules of brunner s glands with a dilatation of few glands .", "gross examination of the specimen revealed circumferential thickening of the second part of the duodenum and bulky head of the pancreas . cut", "a biopsy of duodenum was performed by the same procedure which was diagnosed as well differentiated adenocarcinoma .", "this patient underwent radical surgery ( whipple s procedure ) at our institute with clinical diagnosis of carcinoma periampullary region and the specimen was sent for histopathological examination ." ], [ "ductal malignancy arising from brunner gland adenoma has been reported in one case which is a very rare circumstance ( 0.5% ) .", "the association of this tumor with uremia and chronic pancreatitis has also been reported . in a study of patients undergoing pancreaticoduodenectomy , 76% of the patients had diffuse hyperplasia of brunner s gland , raising the question whether this is an adaptation to pancreatic insufficiency .", "a definite relationship has not yet been proven because of the high prevalence of helicobacter pylori and rarity of this lesion in the general population . \n \n initially , the hyperplasia of brunner s gland can be focal , localized , and solitary usually involving a lobule", "support to this hypothesis is not rationalized as lymphocytes may be present in normal submucosa of the gastrointestinal tract . in a study on the role of helicobacter pylori infection in the pathogenesis of bgh , 5 of 7 cases with bgh had concurrent helicobacter pylori infection .", "\n brunner glands are branched acinotubular glands with submucosal location , found exclusively between the pyloric ring and the papillae of vater .", "endoscopically these can be nodular , polypoid or diffuse with thickening of the duodenal wall . due to this presentation , these lesions can be misdiagnosed as gastrointestinal stromal tumor ( gist ) , lymphoma , carcinoid , peutz jeghers polyp , prolapsed pyloric mucosa , or aberrant pancreatic tissue .", "brunner gland adenoma in the duodenal wall with a focus of atypical cells supported by mib-1 and p53 positivity has also been reported . \n \n" ], [], [] ]

[ [ "metastasis of transitional cell carcinoma ( tcc ) of the renal pelvis to the eye is a very rare event and has only been reported in one case in the literature .", "we present a case report of a male patient with unilateral choroidal metastasis secondary to tcc of the renal pelvis .", "once diagnosed , these cases usually show widespread metastases and carry a very poor prognosis .", "review of the relevant literature will be addressed to highlight the involvement of the choroid in cases of metastatic disease , the unusual presentation of tcc , diagnostic methods , and the various therapeutic modalities used to treat these cases ." ], [ "all of these clinical features are suggestive of the clinical diagnosis of left choroidal metastasis .", "external beam radiation therapy ( ebrt ) is a common mode of treatment and will be considered if there is no improvement of visual symptoms with chemotherapy .", "imaging studies were done , which revealed multiple pulmonary and liver metastasis , subcutaneous metastasis , multiple lymphadenopathies , and left renal upper pole mass ( fig 2 ) .", "a 61-year - old male , who has a history of congestive heart failure , is a nonsmoker , and has no significant family history of malignancies , presented to the ophthalmology clinic with sudden - onset loss of vision of the left eye associated with intermittent left eye pain , relieved by analgesics" ], [ "choroidal metastasis is the most common intraocular malignancy , due to its rich vascular supply and high oxygen concentration [ 4 , 5 ] .", "choroidal metastasis is commonly associated with disseminated disease and , unfortunately , carries a very poor prognosis .", "less common primary cancers include the thyroid , prostate , kidney , testicles , pancreas , ovary , and liver .", "the treatment of choroidal metastasis should be individually tailored , taking into consideration the patient 's systemic state , disease activity , and the presence of visual symptoms .", "local therapy has been reported to be safe , maintaining visual functions without the systemic side effects of chemotherapy ." ], [ "choroidal metastasis related to tcc of the renal pelvis is an extremely rare event and is associated with widespread disease and a very poor prognosis", ". systemic chemotherapy with carboplatin and gemcitabine is a palliative treatment option for this patient .", "ebrt offers local palliation and will be considered according to the patient 's visual response to chemotherapy ." ], [], [] ]

[ [ "a review of the literature revealed no study that assessed the association between ocd ( based on the obsessive compulsive inventory - child version ( oci - cv ) ) and ckd .", "more specifically , one disorder whose relationship with ckd in children has not been adequately examined is obsessive - compulsive disorder ( ocd ) .", "obsessive - compulsive disorder ( ocd ) is a chronic disabling illness characterized by repetitive ritualistic behaviors over which the patients have little or no control ( 13 , 14 ) .", "chronic kidney disease ( ckd ) is defined as the slow and steady damage of kidney function in an irreversible manner , which ultimately results in end - stage renal disease ( esrd ) ( 1 , 2 ) .", "based on the available literature , patients with ckd who develop psychiatric and cognitive disorders face longer hospitalization times , more health complications , and greater mortality compared to other patients at the same stage without these disorders ( 11 , 12 ) . therefore , proper diagnosis of psychiatric and cognitive disorders in these patients is paramount .", "the causes of ckd are very different in children than in adults . in a recent north american pediatric renal transplant cooperative study ( naprtcs ) , congenital causes , including congenital anomalies of the kidney and urinary tract ( cakut ) ( 48% ) and hereditary nephropathies ( 10% ) , were the most common causes of ckd in the children ( 3 ) . based on previous studies , such a chronic disorder impairs the quality of life of children due to the development of various clinical symptoms , especially developmental disorders and psychiatric disorders ( 4 - 6 ) ." ], [ "the aim of this study was to investigate ocd in children with early stages of ckd and to compare it with healthy children ." ], [ "this case - control study was performed on 160 children in the age bracket of 7 to 17 years old who were referred to the pediatric clinic of amir kabir hospital in arak ( iran ) in 2015 .", "the oci - cv was modestly correlated with obsessive compulsive symptom severity on the children s yale - brown obsessive compulsive scale ( cy - bocs ) , as well as with clinician - reported ocd severity ( 19 , 20 ) .", "the oci - cv is considered to be a reliable and valid method for identifying children with ocd .", "the persian version of the oci - cv questionnaire was tested for reliability in a pilot study by the researchers with 30 patients in each of the case and control groups ; the cronbach s alpha was 0.89 .", "ocd in children was evaluated using the obsessive compulsive inventory - child version ( oci - cv ) by a psychologist ( consultant ) .", "eighty children with early stages of ckd ( stages 1 , 2 and 3 ) comprised the case group , and the control group consisted of 80 healthy children without ckd ; children were included in the study based on the inclusion criteria ." ], [ "of the 160 subjects , 86 ( 53.75% ) were boys and 74 ( 46.25% ) were girls . in the group comprised of children with ckd ,", "the mean weight , height , and bmi of the children were 38.15 6.8 kg , 127.61 8.5 cm , and 17.31 3.52 , respectively .", "moreover , the mean total scores for the oci - cv of the children with ckd at 15.32 7.69 was significantly higher than those of the healthy ones at 11.12 2.54 ( p = 0.021 ) . nevertheless , the mean scores of obsessing ( p = 0.11 ) , hoarding ( p = 0.117 ) , washing ( p = 0.211 ) , and neutralizing ( p = 0.41 ) were not significantly different between the case and control groups ( table 2 and figure 1 ) .", "however , the maternal educational level was significantly different between the two groups ( p = 0.001 ) , so that 30 ( 37.5% ) and 37 ( 46.25% ) of mothers in the group of the children with ckd had college and high school education , respectively , whereas 16 ( 20% ) and 50 ( 62.5% ) of the mothers in the control group had college and high school education , respectively .", "the duration of the disease and the age of diagnosis were 1.48 2.12 and 6.9 5.4 years , respectively .", "the mean scores of doubting / checking ( case : 3.52 2.54 , control : 2.5 2.32 , p = 0.007 ) and ordering ( case : 2.59 1.81 , control : 1.5 2.56 , p = 0.005 ) of the children with ckd was significantly higher than the scores of the healthy ones .", "according to the results of spearman s test , there was significant correlation between the duration of ckd and doubting / checking ( p = 0.004 , correlation coefficient ( cc ) : 0.4 ) , obsessing ( p = 0.06 , cc : 0.02 ) , washing ( p = 0.031 , cc : 0.8 ) , ordering ( p = 0.001 , cc : 0.2 ) , and the total scores of the oci - cv questionnaire ( p = 0.04 , cc : 0.4 ) ( table 3 ) ." ], [ "the risk of ocd among children with ckd is significantly higher than the risk among healthy children .", "according to the results of the current study , ocd and certain subscales of this disorder are more likely to occur in children with early stages of ckd than in healthy children . in this respect , doubting / checking and ordering had higher rates among children with ckd than among healthy children .", "similarly , the results of this study were indicative of the higher prevalence of ocd as an anxiety disorder in children with ckd as compared to healthy children .", "although there have been a number of studies assessing the psychiatric disorders in children with ckd , no study has been carried out on the relationship between ocd and ckd based on the oci - cv .", ", it can be argued that the risk of various psychiatric disorders in children with ckd at early stages and children with esrd tend to be significantly higher as compared to healthy children ." ] ]

[ [ "problems with shoe wear have long been recognized as an endemic issue among the geriatric population with a prevalence rate of nearly 80% .", "this review aims to form a general basis of understanding footwear - associated foot pathologies pertaining to the elderly patients .", "the increased risk of falls may highlight the need to promote preventative measures to combat this issue .", "consequentially , this leads to physical inactivity , which is cited as one of the first signs of deterioration and the overall decrease in quality of life .", "moreover , some studies have linked physical inactivity to suicide , depression , and increased risk of cardiovascular - related problems .", "multiple etiologies have been noted to cause foot problems , and studies have indicated ill - fitting shoes as one of the major underlying cause .", "are often severely physically impaired , making it increasingly difficult to perform activities of daily living ." ], [ "finally , the uneven pressure provoked by ill - fitting footwear has been documented as a key factor that can cause , accelerate , or exacerbate foot - related conditions .", "elderly individuals with preexisting clinical conditions such as diabetes , neuropathies , and musculoskeletal disorders are at a higher risk of developing foot problems when compared to normal , healthy individuals .", "furthermore , factors such as exercise and living conditions contribute to the development of foot problems ." ], [ "these studies seem to support the use of footwear with low heels , slip - resistant soles and wider frames to ensure comfort , better balance , and reduced risk of injury in the elderly population . in the event of multiple deformities , an individual may benefit from the combination of both extra - depth , wide , and low - heeled footwear to increase foot stability and facilitate balance .", "low - heeled footwear is known to reduce the risk of falls , likely due to the associated lowering of the center of gravity . while assessing different footwear , athletic and canvas shoes ( sneakers )", "operative management is considered only when conservative measures fail to relieve progressed , advanced - stage pathology .", "nonoperative approaches have been employed as the first line of treatment for the most common foot pathologies .", "measures are taken to adjust or alleviate pressure from the affected area . as a result ,", "as an extra preventative measure , better fitting footwear with slip - resistant soles is recommended both inside and outside the household to reduce the risk of falls . taken together ,", "special consideration is given to diabetic patients , who have a higher risk of developing ulcerations due to peripheral neuropathy ." ], [ "furthermore , retail stores often do not stock the customized shoes ( ie , extra wide ) needed for elderly customers , making availability an issue for elderly patients .", "the neglect of appropriate footwear in the elderly has been linked to early amputation , and in rare cases , early demise . \n to help alleviate the financial burden", "deteriorating health conditions followed by reduced physical activity can lead to a shift in clinical care , one that emphasizes the management of illness . in the face of such socioeconomic constraints ,", "millions of elderly individuals live at or below the poverty level . in fact , women older than 75 years are 3 times more likely to become poor . without established financial programs such as social security , nearly half of all elderly individuals would be considered poor today .", ", elderly patients enrolled in medicare part b may benefit from the medical coverage of certain medical supplies and preventative services .", "changes in living conditions ( ie , community homes , nursing homes , etc ) can often worsen the socioeconomic status of elderly patients .", "the use of appropriate shoe wear in the elderly patients is related to the socioeconomic factors .", "such patients are entitled to a pair of custom - molded shoes , 3 pairs of inserts , or a pair of extra - depth shoes per calendar year ." ], [ "ultimately , the noticeable decrease in physical activity in the elderly patients has been linked to depression and an overall decline health and quality of life .", "clinically , preventative measures such as appropriate footwear should be continually emphasized to stop or delay the progression of some foot problems .", "these pathologies , in return , have contributed to the growing risk of even more serious injuries such as falls and fractures .", "while recommending appropriate footwear is a cost - effective approach when compared to other options , it is often hindered by socioeconomic obstacles .", "nevertheless , studies have shown that it can be a vital step to ensure prolonged musculoskeletal and overall health among the elderly patients .", ". some of these hazards such as wet pavements and bad weather conditions are capable of causing serious injury ." ] ]

[ [ "here , we examined the function of smyd3 and setd7 in heart development in zebrafish . collectively , our results demonstrate that smyd3 and setd7 function synergistically for skeletal muscle development and non - redundantly for heart morphogenesis .", "recent reports suggest that epigenetic regulation modulates genetic program during differentiation and development of various organs including heart and somitic lineages ( wamstad et al . , 2012 ) .", "for instance , modifications of histone substantially alter the accessibility and structure of chromatin , therefore modifying transcriptional activity of specific gene clusters .", "especially , set domain is important for histone lysine methylation activity and mynd domain can mediate the protein - protein interaction and bind to dna motifs ." ], [ "staining were stopped according to desired detection status and imaged in 75% glycerol solution for proper orientation . to generate the synthetic smyd3 and setd7 mrnas , we first cloned the full open reading frames ( orf ) of smyd3 and setd7 into pcs2 + expression vector , which have sp6 promoter sequence and sv40 poly - a tail sequence for in vitro transcription .", "zebrafish ab strain as wild - type control for all experiments , expect the experiments using tg(cmlc2:egfp ) line .", "zebrafish strains were maintained as previously described ( westerfield , 1993 ) . to visualize the heart morphology in live embryos , tg(cmlc2:egfp )", "the sequences of mos used are control mo , 5-cctcttacctcagttacaatttata-3 ; smyd3 mo , 5-aagagctcttacctgacactgaacg-3 ; and setd7 mo , 5-agcttctcgtaccttccaccacttc-3. embryos injected mos were observed or collected at desired developmental stages for further experiment . to make digoxigenin - labelled antisense ribo - probe , zebrafish smyd1a ( nm_205540.1 ) , smyd2 ( nm_001013550.1 ) , smyd3", "injection was achieved at 12 cell stages as optimal concentrations ( about 100200 pg / embryo ) .", "whole mount in situ hybridization were routinely performed as previously described ( thisse and thisse , 2008 ) . as brief ," ], [ "zebrafish ab strain as wild - type control for all experiments , expect the experiments using tg(cmlc2:egfp ) line .", "zebrafish strains were maintained as previously described ( westerfield , 1993 ) . to visualize the heart morphology in live embryos , tg(cmlc2:egfp )" ], [ "the sequences of mos used are control mo , 5-cctcttacctcagttacaatttata-3 ; smyd3 mo , 5-aagagctcttacctgacactgaacg-3 ; and setd7 mo , 5-agcttctcgtaccttccaccacttc-3. embryos injected mos were observed or collected at desired developmental stages for further experiment .", "mos were injected with 0.1% phenol - red solution into zebrafish embryos at 12 cell stages as desired concentrations .", "control , smyd3 , and setd7 mos were designed by author and ordered to genetools company ." ], [ "to make digoxigenin - labelled antisense ribo - probe , zebrafish smyd1a ( nm_205540.1 ) , smyd2 ( nm_001013550.1 ) , smyd3 ( nm_001037400.1 ) and setd7 ( nm_001002456.1 ) full orfs were cloned into pgem - t vector ( promega ) after amplification of 24 hpf cdna .", "hybridization reaction was carried out at 65c , and the detection of hybridized rna probe was achieved by anti - digoxigenin fab fragment conjugated to alkaline phosphatase and bcip / nbt substrate ( roche ) .", "whole mount in situ hybridization were routinely performed as previously described ( thisse and thisse , 2008 ) . as brief ,", "zebrfish embryos were fixed by 4% paraformaldehyde ( pfa ) and stored in methanol . to experiment , fixed embryos washed and digested with proteinase k solution as desired concentration and times .", "staining were stopped according to desired detection status and imaged in 75% glycerol solution for proper orientation ." ], [ "to generate the synthetic smyd3 and setd7 mrnas , we first cloned the full open reading frames ( orf ) of smyd3 and setd7 into pcs2 + expression vector , which have sp6 promoter sequence and sv40 poly - a tail sequence for in vitro transcription .", "injection was achieved at 12 cell stages as optimal concentrations ( about 100200 pg / embryo ) .", "synthetic mrna was diluted as 100 g / ml and phenol red was added prior to injection as 0.1% solution .", "these plasmids were cut by noti digestion to linearize , and capping mrna were produced using m7g(5)ppp(5)g ( roche , germany ) and sp6 rna polymerase ( roche , germany ) ." ], [ "collectively , our results show that smyd3 and setd7 likely function synergistically in zebrafish development . moreover , our data suggest that heart development is more sensitive than somitogenesis to the decrease of smyd3 and setd7 levels . to test whether the developing heart defects in the smyd3-and setd7-deficient embryos are caused by the expressional changes of early cardiac muscle genes", "since similar developmental defects were observed in embryos with either excessive or reduced level of smdy3 and/or setd7 activity , it appears that appropriate level of histone methylation is critical to ensure the formation of cardiac and skeletal muscle in zebrafish .", "our results indicate that methylation can provide essential regulatory input during organ development in zebrafish .", "therefore , it appears that excessive h3k4 methyltransferase activity can lead to defects in heart and skeletal muscle development in zebrafish . taken together ,", "collectively , our results illustrate that the proper activities of h3k4 methyltransferases , specifically smyd3 and setd7 , are important for zebrafish heart formation . during histone", "this finding suggests that smyd3 and setd7 are dispensable for proper expression of early cardiac muscle genes and differentiation of cardiac precursor cells . to investigate whether enforced expression of smyd3 and setd7 causes the cardiac defect in zebrafish , synthetic mrna encoding smyd3 or setd7" ], [ "our data presented here indicates that proper level of histone methylation , which is mediated by a series of enzymes commonly known as hmts , including smyd3 , and setd7 appears to be essential for heart development . during zebrafish development", "heart morphogenesis in vertebrate development is a highly complicated event that achieved by correct cell specification , migration , proliferation , apoptosis , and transition as well as controlled beating of heart myocytes ( barnett et al . , 2012 ) .", ", we have shown the knock - down and overexpression phenotypes of smyd3 and setd7 in zebrafish development .", "these findings extend our current knowledge of the roles of hmts and increase our understanding of the functional mechanism of hmts in heart development ." ] ]

[ [ "we will discuss the development of genetic techniques that bridge the divide between these two approaches and allow the targeting of molecular changes specifically to anatomically dispersed neural representations that are activated by discrete environmental stimuli .", "these new tools allow the establishment of causal relationships between the activation of sparsely distributed neural ensembles and changes at the behavioral level .", "they have been approached by a variety of techniques that fall into two broad categories , watching brain activity and disrupting brain function . in this review", "both pharmacological and genetic manipulations have been used to test ideas about the cellular signaling mechanisms that underlie behavioral plasticity ." ], [ "the goal of this review is to discuss recent attempts to develop approaches that allow similar convergent molecular and physiological access to the more dispersed neural representations of the mammalian brain .", "the aplysia neurons are primary sensory neurons and their response properties can be predicted by their physical location in the ganglion .", "the sensory neuron cell bodies are located adjacent to each other in a cluster and possess similar biochemistry and response properties . the bottom panel represents the hippocampal circuit of the mammalian brain .", "the behavioral plasticity of the withdrawal reflex is controlled by synaptic plasticity within these sensory neurons . because of the uniformity and anatomical isolation of this group of cells , it has been possible to apply techniques for both watching and manipulating neurons within the context of a defined circuit ( representation ) in a behaving animal ." ], [ "we suggested that neurons activated by the us ( shock ) but also receiving weak cs inputs were altered during learning such that the cs alone could now activate them . in this way presentation of the cs alone after learning would recapitulate a portion of the aversive us leading to downstream fear responses .", "however , by using a regulatable and binary genetic system , it should be relatively easy to introduce additional effector transgenes into the mice to control the activity or biochemistry of these neurons and directly test their role in memory .", "one technique that has been used for many years to watch brain activity has taken advantage of a class of immediate early genes or iegs that are expressed in response to high - level neural firing ( sagar et al . , 1988 ) .", "thus the expression pattern of iegs in brain sections from an animal provides a record of the neural activity from several hours prior to sacrifice and has been used extensively to map brain activation from a wide variety of environmental stimulation and in learning and memory relevant paradigms ( guzowski et al . , 2005 ) .", "these results demonstrate that memory retrieval results in a reactivation of some of the same neurons that were active during the initial learning .", "we hypothesized that these reactivated neurons represent a component of the memory trace for conditioned fear . to test this idea we weakened the strength of the memory by extinction training ; giving repeated cs presentations without the shock us .", "we found that the number of reactivated neurons in the amygdala , a region critical in fear conditioning ( ledoux , 2007 ) , correlated with the retrieval of the fear memory ." ], [ "in one recent study , ( han et al . , 2007 ) , it was found that over expression of the transcription factor creb in neurons resulted in their preferential recruitment into a fear memory trace . in this study ,", "the use of neural activity to introduce genetic alterations into neurons offers the possibility of obtaining direct molecular control over the neurons that participate in a specific neural representation or memory trace . an alternate approach that realized this goal took advantage of the finding that certain molecular manipulations could recruit neurons to participate in control of a specific memory .", "this is the first example of the disruption of a specific memory within a distributed network . disrupting a specific memory in the mouse .", "this result suggests that these creb over expressing neurons were predisposed to participate in the memory trace ." ], [ "while the ability of creb over expression to recruit neurons to participate in a specific memory is interesting in its own right , it would be useful to have an approach to manipulate neurons that were naturally activated by any general environmental stimulus .", "nevertheless , it demonstrates the general principles of this approach , which could be combined with the host of recently developed genetic regulators of neural activity .", "while the behavioral results in this study are intriguing and the linkage to cfos based expression provides a potentially general approach for manipulating discrete neural representations , there are a number of important questions that remain to be addressed with this technique .", "this has recently been accomplished using a technique in which neurons expressing -galactosidase can be specifically disrupted with a pharmacological agent ( koya et al . , 2009 ) .", "they examined context specific sensitization to cocaine , which is an associative paradigm where the response to a drug of abuse is potentiated when it is administered in the same environment in which it has been repeatedly taken ." ], [ "a potential answer to this question was suggested by frey and morris in studies of long - term potentiation ( ltp ) , a form of synaptic plasticity thought by many to underlie memory ( frey and morris , 1997 , 1998 ) .", "a number of studies have implicated the regulated trafficking of the glutamate receptor glur1 to synapses as an important mechanism in both ltp and fear learning ( kessels and malinow , 2009 ) .", "we recently used the cfos based genetic approach to demonstrate a similar mechanism in behavioral learning and memory .", "this experiment demonstrates how genetic tools can be used to image a specific molecular event selectively within an activated neural circuit .", "this is indicative of a synaptic tagging event acting in behavioral memory similar to that described for ltp ( frey and morris , 1997 ) . learning regulated targeting of glutamate receptors ." ], [ "the ability to genetically manipulate activated neuronal ensembles or neurons participating in a sparsely encoded memory trace offers a number of advantages that are only beginning to be realized .", "the increased specificity along with the new genetic tools and biochemical tagging should provide a new level of circuit analysis in the brain and break down the barrier between watching neural firing and manipulating neural function .", "finally , the ability to genetically alter activated neural ensembles provides an entre into a more specific biochemistry of the brain . in the glur1 trafficking studies discussed above , the gfp tagged receptor", "the combination of these new tools with activity based genetic delivery and multi time point brain activity mapping at cellular resolution will open up a variety of new questions to experimental analysis . to return to the initial discussion of neural representations ," ], [ "the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest ." ] ]

[ [ "the relationships of angiogenesis with cancer have special relevance , since angiogenesis has been described as one of the hallmarks of cancer , playing an essential role in tumour growth , invasion , and metastasis .", "national cancer institute database showed that in august 1999 a total of 20 angiogenesis inhibitors were being tested in clinical trials . remarkably , most of them were monotherapies with the antiangiogenic agent , and those compounds that had then reached the phase iii , including several inhibitors of matrix metalloproteinases , were discontinued due to their lack of activity or the appearance of undesirable toxicities . in spite of the great number of angiogenesis inhibitors described so far ( estimated to be > 300 drug candidates in 2001 ) , and the interesting results obtained in experimental models , even showing complete tumour regressions in pre - clinical studies , modest or even negative results emerged from the first generation of compounds entered in clinical trials .", "nevertheless , there is no reason for premature pessimism , as revealed by current ongoing trials and the clinical developmental status of anti - angiogenic drugs .", "since tumour blood vessels show many differences from normal vessels and are not genetically unstable , they are potential targets for therapy of all types of cancer . due to the pivotal role played by endothelial cells in tumour angiogenesis ,", "however , deregulated , abnormal angiogenesis is involved in many pathological processes [ 1 , 2 ] .", "the complex sequence of events involved in angiogenesis is related to changes in endothelial cell biosignalling ." ], [ "finally , in this brief analysis of the rationale behind the failure of the first generation of antiangiogenic agents , concern should be given to the way in which scientists communicate their findings to society .", "angiogenesis research is an especially competitive area in which the promising preclinical results have been very often prematurely amplified by mass - media releases .", "these include flaws in the methods used to select these inhibitors and in the design of the clinical trials to test their effects , as well as an oversimplified view of tumour vasculature pathophysiology .", "a clinical challenge in antiangiogenesis is the finding of biological markers that help to identify subsets of patients more likely to respond to a given antiangiogenic therapy , as well as to determine optimal dosing of therapy , to detect early clinical benefit or emerging resistances and to decide whether to change therapy in second - line treatments .", "the high prevalence of cancer and the extremely high sensitivity of society towards this primary medical problem facilitate that great expectations could lead to deep disappointment ." ], [ "therefore , a multidrug approach might be more successful than monotherapy . the combined used of several antiangiogenic compounds targeting different steps of angiogenesis should be explored .", "it seems that , after a period of flawing interest , antiangiogenic compounds have regained their place in the centre of anticancer treatment trials , as shown by the eastern cooperative oncology group portfolio of clinical trials . from the results obtained so far in clinical trials , it can be concluded that the future clinical success of angiogenesis inhibitors could be related to their use in combination with chemotherapy or radiotherapy .", "a second generation of antiangiogenic trials is beginning to show highly significant potential [ 8 , 35 ] . the first study showing phase", "these impressive results led the fda to approve the use of bevacizumab in patients with metastatic colorectal cancer and they have been finally published in the form of a research article in the new england journal of medicine . however , as stated in the accompanying editorial , although it is tempting to attribute the effect of bevacizumab to a direct antiangiogenic mechanism , the validity of this assumption is presently uncertain . once more , mass - media releases have led to unrealistically high expectations . as commented in the aforementioned editorial ,", "bevacizumab in combination with paclitaxel and carboplatin treatment was approved for the first - line treatment of patients with non - small cell lung cancer" ], [ ", the kinetics of these cells in peripheral blood is suggested to be useful surrogate markers of pathological angiogenesis with potential application for the monitoring of antian - giogenic therapy response .", "preclinical studies have shown that circulating endothelial cells , which are probably derived from blood vessel wall turnover , and circulating endothelial progenitors kinetics correlate well with several standard laboratory assays , that can not be used in humans .", "the initial suggestion that variation in the levels of circulating endothelial progenitor cells could be a useful surrogate marker to monitor angiogenesis has been confirmed and extended in an outstanding report published in cancer cell .", "this report provides evidence that the levels of circulating endothelial progenitor cells are genetically predetermined and regulated by regulators of angiogenesis , including vegf , tie-2 and thrombospondin-1 .", "moreover , antiangiogenic therapy can be optimized by monitoring the levels of both circulating endothelial cells and circulating endothelial progenitor cells [ 13 , 25 ] . therefore", "as stated before , reliable biomarkers are strongly needed to validate the efficacy of antiangiogenic therapy , to identify responsive patients and optimal doses , to predict efficacy of regimens that include anti - angiogenic agents , and to detect and prevent tumour escape ." ], [ "antiangiogenic cancer therapy : past and future ; clinical trial lessons the development of new and better models for the in vivo assay of potential inhibitors of human angio - genesis should be considered a priority in this field of research .", "how much antiangiogenic therapy will be incorporated in the future to the treatment of cancer patients depends on further advances in the understanding of the molecular mechanisms involved in tumour angio - genesis , the development of standardized methods to assess surrogate predictive markers of response , and the capability of performing a new generation of appropriately designed clinical studies . a convergence of the efforts carried out in basic , applied and clinical research would contribute to achieve these goals .", "consequently , the extensive use of correlative studies in the early phases of drug development to establish surrogate biomarkers for use in efficacy trials is strongly recommended .", "however , in spite of the fact that past clinical studies have shown that many angiogenesis inhibitors can be given safely to patients , more long - term toxicity studies are needed .", "in fact , monotherapies with antiangiogenic compounds could be useful as adjuvant treatments in situations of minimal residual disease following either cytore - ductive surgery or cytotoxic treatment ." ] ]

[ [ "quantitative real - time pcr ( qrt - pcr ) has been performed to determine the expression of these mirnas . for mapping the identified mirnas , genome of vitis vinifera", "the current study has employed the deep sequencing strategy in an attempt to effectively identify conserved and novel jute mirnas .", "regulation of gene expression is one of the most enigmatic facets of molecular genetics that results in intricate appearance of a biological entity .", "small noncoding rnas of 1840 nucleotides ( nt ) in size have been proved to play a vital role in a remarkably wide range of biological processes , including cell proliferation , developmental timing and patterning , chromatin modification , genome rearrangement , and stress response in plants and animals ." ], [ "the identified known and potential novel mirna candidates in jute , stem - loop reverse transcription - pcr was performed .", "the targets of mirnas were further validated by a well - recognized mirna - target prediction tool : psrna target .", "prediction of novel mirna was done using prediction software , mireap ( http://sourceforge.net/projects/mireap/ ) , developed by bgi by taking into consideration secondary structure , cleavage position of dicer protein , and minimum free energy of the unannotated small rna tags .", "strategic conditions for selecting unique mirna are as follows : ( i ) the tags which are to be used to predict novel mirna should be from unannotated tags which can match reference genome ( vitis vinifera ) , from the tags which align to introns as well as antisense exons ; ( ii ) genes , whose sequences satisfy the above standards and their secondary structures which allow hairpin mirnas to fold within them and the presence of mature mirnas in one arm of the hairpin precursors , are considered as candidate genes for mirna ; ( iii ) the possible candidate mature mirna strand contains 2-nucleotide 3 overhang ; ( iv ) hairpin precursors of the candidate mirnas are devoid of large internal loops or bulges ; ( v ) secondary structures of the hairpins are stable , with the minimum folding energy ( mfe ) lower than or equal to 20 kcal / mol .", "later , rna samples were sent to beijing genome institute ( bgi , shenzhen , china ) for deep sequencing of small rna by illumina hiseq high - throughput sequencing platform . in short ," ], [ "characteristic hairpin structure of mirna precursor was used to predict novel mirna with prediction software mireap ( http://sourceforge.net/projects/mireap/ ) by exploring the secondary structure , the dicer cleavage site , and the minimum free energy of the unannotated small rna tags which could be mapped to the reference vitis vinifera genome . predicted secondary structures were further validated by mfold ( supplementary file-3 ) and novel mirnas were identified based on the selection criteria described in section 2 .", "in order to identify micrornas in jute , rna was isolated from the total tissue of four - day seedlings and subjected to illumina hiseq high - throughput sequencing by synthesis ( sbs ) technology . among a total of 16912862 raw reads ,", "the novel mirnas in jute were identified from unannotated tags by using mireap , software developed by bgi ( described in section 2 ) . in the absence of the complete genome sequence and with practically no information on mirna of jute in mirbase", "novel mirnas usually have lower levels of expression than the conserved mirnas , as evident from findings of several plant species like soybean , brassica napus , maize , arabidopsis , and wheat [ 59 , 6164 ] . for a precise elucidation of the role of mirnas , target identification and determination of their biological functions", "as illustrated by kegg pathway analysis ( supplementary file-8 ) , the predicted target genes of jute mirnas were found to be involved in 42 different pathways ." ], [ "while a large amount of mirnas are reported and deposited in databases from different plants , mirna associated research in jute is still to be instigated . without the genome sequence of jute at hand , identification of mirna and their targets in jute by deep sequencing of small rnas", "we have predicted target genes for known and potential new mirnas identified in this study using the genome of vitis vinifera as a reference .", "sequencing frequencies for mirnas in a library can be used as an index for estimating the relative abundance of mirnas .", "most of the target genes for conserved mirna families predicted in jute have already been confirmed in model plants , as target genes are commonly conserved [ 78 , 80 ] .", "discrepancies in the expression pattern of some mirnas found by deep sequencing and qpcr can be attributed to practical differences between the sensitivity and specificity of these two techniques . the sensitivity and large dynamic range of next generation sequencing ( ngs ) , along with its consistent prediction of fold changes when compared with gold - standard qpcr , support its use for discovery - oriented and exploratory mirna profiling experiments [ 84 , 85 ] . to evaluate and outline a putative function for a mirna in plants ," ], [ "this set of experimentations for identification of mirnas and their potential targets can initiate further study on understanding the mechanisms of regulation of jute mirna ." ] ]

[ [ "this large chart review was undertaken to examine our experience with open laparoscopy and to determine whether preoperative characteristics can predict open laparoscopic entry complication .", "these complications arise due to the normal anatomic relationship of the periumbilical site to the underlying great vessels and viscera and are particularly problematic in patients with adhesions or at extremes of body weight . additionally , delay in diagnosis of bowel injuries frequently sited with this closed technique accounts for significant morbidity and mortality .", "the use of laparoscopy in gynecology has developed into a vital tool for the evaluation and treatment of pelvic pathology .", "the predominant method of entry in gynecologic surgery worldwide remains a closed technique , with or without pneumoperitoneum .", "hasson proposed its potential benefits to be the avoidance of blind insertion of the veress needle and bladed trocar , prevention of preperitoneal insufflation and gas embolism , guaranteed pneumoperitoneum , and a more anatomical repair of the abdominal wall . since that time", "this approach unfortunately has been demonstrated in multiple studies to have the potential for visceral and vascular injury due to the blind insertion of veress needles or trocars ." ], [ "we completed a retrospective chart review of all patients who underwent laparoscopy via an open technique at the mayo clinic arizona in the department of gynecology ( 8 surgeons ) from january 1 , 1998 through december 31 , 2006 .", "the open laparoscopic technique used in this series is similar to that originally described by hasson and is as follows : the umbilicus is held and everted with 2 allis forceps .", "closure of the umbilical entry site is performed with direct visualization and identification of the fascial layer .", "intraoperative complications ( bowel and vascular injury , failure to enter ) , postoperative complications ( hernia , hematoma , cellulitis , abscess , cosmetic issues ) , body mass index ( bmi ) , number of previous abdominal surgeries , and length of follow - up were extracted from charts .", "finally , the laparoscope is introduced and the organs below the entry site are inspected as is the remainder of the abdominal cavity .", "a vertical skin incision , 10-mm to 15-mm long , is created at the deepest portion of the umbilicus .", "a 0-polyglactin suture on a # 2 urologic needle is used for the fascial layer , and a 40 polyglactin suture is used for skin approximation ." ], [ "a significant association was noted between umbilical infection and previous abdominal surgery ( p=0.049 ) , and between umbilical hernia and obesity ( p=0.024 ) .", "patients with subsequent umbilical hernias were subclassified into symptomatic ( noted by a physician or patient ) or asymptomatic ( discovered serendipitously at a subsequent surgery ) ( table 1 ) .", "patients with umbilical infection were subclassified based on whether the diagnosis was made over the phone due to patient complaints of erythema or drainage , by examination and diagnosis of cellulitis , or an umbilical abscess requiring evacuation .", "fisher 's exact test was used to determine the association between each of the recorded complications and the number of previous abdominal surgeries and obesity ( bmi>30 ) ( table 2 ) ." ], [ "this chart review confirms previous findings of case series , literature reviews , and meta - analyses of the complications associated with open laparoscopic entry .", "similar rates of umbilical infection and hernia occurred with both techniques . to date , there are no reports of fatal vascular injuries and only 2 instances of nonfatal major vascular injuries in the literature associated with the use of the open technique .", "a large dutch review of 12,444 cases of open laparoscopy culled from 6 previously published case series found a 0.048% rate of enterotomy and no cases of vascular injury or gas embolism ." ], [ "this case series confirms previous reports of the low risk of enterotomy , absence of fatal vascular injury , and comparable rates of umbilical infection / hernia associated with an open entry technique .", "the use of an open laparoscopic entry is advocated because it is a safe , simple means of accessing the peritoneal cavity .", "the rapid recognition of enterotomy with this entry technique , and the utility of this technique in obese patients or those with previous abdominal procedures are additional advantages ." ] ]

[ [ "this review will collate vascular remodeling during ph , mirna biogenesis , recent advances on mirna modulation in ph , therapeutic opportunity , and conclusion .", "indeed , an emerging body of evidence demonstrates that a fine balance in mirna levels seems to be a fundamental to maintaining homeostasis in the pulmonary vasculature and an imbalance with mirna level playing a critical role in the pathogenesis of ph by regulating a set of targeted genes .", "evolving evidence indicates that dysregulation of micrornas ( mirna or mir ) contributes to ph pathogenesis [ 1924 ] .", "it is an enigmatic vascular disease and the pathogenesis of ph is multifactorial of origin and , hence , is categorized as idiopathic type [ 14 ] . as ph develops in a wide variety of clinical circumstances and is associated with diverse histological manifestations , a classification system is developed [ 5 , 6 ] . the dana point expert group has published a consensus of ph classification based on pathology , survival , natural history / epidemiology , etiology , and response to the treatment . among them ," ], [ ", the bound mirna strand ( called the guide strand ) dictates mirisc to interact with partially complementary sequences in target transcripts ( localized within the 3utr ) and primarily triggers mrna deadenylation and degradation .", "the mirna / mirna duplexes are then incorporated into a ribonucleoprotein ( rnp ) complex called mirisc ( rna - induced silencing complex)that plays a critical role in the mirna - mediated mechanism of gene regulation . during assembly process of the mirisc ,", "the mirna(s ) are composed of a vast family of short , noncoding rnas ( ~22 nucleotide long ) ." ], [ "micrornas ( mirnas ) are small , endogenously expressed noncoding rnas that regulate gene expression at posttranscriptional level , via degradation or translational inhibition of their target mrnas [ 37 , 59 ] .", ", a discussion of the roles of mirnas in ph - related signaling pathways is provided .", "emerging evidence indicates that mirnas contribute an important role in the maintenance of pulmonary vascular homeostasis and in the pathogenesis of ph . in the following part", "mirnas are key regulators of a wide range of cellular processes and play a pivotal role in vascular inflammation and cardiovascular pathologies inclusive of ph . from extensive studies from the past few years , it has become apparent that mirnas are expressed in a cell- and tissue - specific manner and are critically involved in various biological processes ." ], [ "although identification of mirnas in vascular diseases like ph is relatively new , but the earliest association connecting vsmc remodeling with mirnas was reported in 2007 .", "an emerging body of evidences suggests that the mirnas play a pivotal role in the vascular cell integrity and plasticity during the progression of ph . here ,", "a panel of mirnas which are shown to modulate smc fate and modulation are listed in table 1 [ 2636 ] .", "ph is broadly considered to be a vascular disease as vasoconstriction in the pulmonary artery is a prime cause for the development of ph .", "in addition to the above mirnas , other mirnas are reported to regulate smc gene expression in hypoxia - induced ph ." ], [ "several animal models in diverse disease pathology showed usefulness of mirnas as target molecules for therapeutic benefit ; this review will focus on vascular remodeling associated with ph . at therapeutic strategic stand - point ,", "tiny rna molecule , have become an important gene modulator of various biochemical , physiological , and cellular functions . as we observed that either deficiency or abundance of a specific mirna or cluster of mirnas contributed a pathological state of many cardiovascular diseases including ph , it is reasonable to accept those mirnas as therapeutic target for diagnosis and therapeutic intervention .", "this is because we can utilize ability of a single mirna to control the expression of multiple ( hundreds ) proteins suggest that changes of a single mirna may influence several signaling pathways associated with pathological disease state .", "while each target is regulated subtly , the additive effect of coordinated regulation of a large suite of transcripts is believed to result in strong phenotypic outputs ." ], [ "over the past few years , it has been demonstrated that mirnas are found in the blood , plasma , urine , platelets , and saliva in a surprisingly stable form [ 9197 ] .", "the stability of mirna in the extracellular environment offers a great opportunity to consider as biomarker at clinical settings . using mirna as a", "circulatory mirnas are considered to be novel promising biomarkers for detection of ph . however , at current stage , using circulatory mirna as diagnostic tool for detecting ph is still in its infancy . the key advantage of circulating mirnas is a noninvasive testing procedure and relies on the stability of mirnas in the circulation and their storage condition .", "the mirnas are circulating freely in the mammalian blood and can be predicted as biomarker for early diagnosis of cardiovascular diseases in humans [ 102 , 105108 ] .", "our study provided the evidence for the first time that circulating mirnas in the setting of ph may be used as early detection parameters for ph ." ], [ "the outcome will validate both physiological and pathological roles of these mirnas during the development and progression of ph prior to consider them for therapeutic intervention or future clinical trials .", "more novel approaches such as combination of argonaute protein immunoprecipitation , deep sequencing , or proteomic profiling approaches are required to identify its potential bona fide targets responsible for its functional impact .", "furthermore , use of disease specific mouse models , conditional transgenic , and knockouts are necessary to elucidate the functional role in vivo and verify its therapeutic potential , both of which remain largely unexplored .", "the characterization of these mirnas under various experimental settings ( in vitro and in vivo ) should be performed along with the human subjects .", "understanding of mirnas role and function in the pulmonary circulation will offer and contribute a great potential to the pathogenesis of ph or pah .", "the mirna signature can be used as a diagnostic tool for the development of therapeutic strategy ." ] ]

[ [ "we present a patient who developed septic shock as a result of p. multocida bacteremia , presumptively from an intra - abdominal infection .", "pasteurella multocida was first described by revolee in 1877 and further characterized by pasteur in 1880 .", "pasteurella species usually have low virulence in humans , but serious manifestations sometimes occur and can lead to bacteremia ." ], [ "after 24 h of admission , patient remained in critical condition and requiring maximum doses of vasopressors , despite of what it seems to be the appropriate empiric antimicrobial therapy .", "no minimal inhibitory concentrations for these antimicrobials were reported . in spite of all medical efforts ,", "blood culture system bact - alert 3d was used for the recovery of the organism ." ], [ "nasopharyngeal colonization with p. multocida with transient bacteremia and seeding of the peritoneal cavity in immunosupressed cat owners could play an important role in the development of sbp .", "p. multocida is a small gram - negative non - spore forming facultative anaerobe organism that is a natural inhabitant of the normal gastrointestinal flora and the upper respiratory tract of wild and domestic animals , especially cats and dogs .", "impaired function of the reticuloendothelial system and the presence of portosystemic shunts in patients with liver disease seem to play a major role in the development of bacteremia .", "outcome is associated with severity of the infection , the extent of the underlying disease and the early initiation of appropriate therapy .", "the majority of p. multocida pneumonia cases occur in elderly patients with underlying chronic pulmonary disease ." ], [ "p. multocida should be included in the microbiologic differential diagnosis in patients with underlying chronic liver diseases who presents with possible intra - abdominal infection , even without history of exposure to domestic animals .", "although cases of bacteremic p. multocida infections has been infrequently reported in the literature , clinicians should considered this organism as an important and potentially lethal pathogen in humans , where it can cause life - threatening infections ." ] ]

[ [ "this review aims to clarify the place of hybrid coronary revascularization in the current therapeutic armamentarium against multivessel coronary artery disease .", "coronary artery bypass grafting ( cabg ) is considered to be the gold standard in patients with multivessel disease and remains the treatment of choice for patients with severe coronary artery disease , including three - vessel or left main coronary artery disease .", "however , because of the use of cardiopulmonary bypass and median sternotomy , cabg is associated with significant surgical trauma leading to a long rehabilitation period and delayed postoperative improvement of quality of life .", "the use of cabg , as compared with both percutaneous coronary intervention ( pci ) and medical therapy , is superior with regard to long - term symptom relief , major adverse cardiac or cerebrovascular events and survival benefit [ 14 ] ." ], [ "the medline / pubmed database was searched in january 2012 using the medical subject headings ( mesh ) for coronary artery disease and angioplasty , balloon , coronary combined with the following free - text keywords : multivessel coronary artery disease , minimally invasive coronary artery bypass , percutaneous coronary intervention , and hybrid coronary revascularization .", "the primary outcome measures were in - hospital major adverse cardiac and cerebrovascular events ( macces ) , packed red blood cells ( prbcs ) transfusion rate , lita patency , hospital length of stay ( los ) , 30-day mortality , survival , and target vessel revascularization ( tvr ) .", "in addition , the period of time between pci and lita to lad bypass grafting and the cost effectiveness of hcr were examined .", "if the need for repeated revascularization involved a coronary artery initially treated with either bypass grafting or pci , this repeated revascularization was considered to be target vessel revascularization . ", "was considered as a patent lita to lad bypass graft , while the fitzgibbon patency class b ( flow limiting ) and c ( occluded ) were defined as a nonpatent lita to lad bypass graft .", "one hundred seventy - seven articles matching these search criteria were found , and the search for additional papers was continued by analysing the reference lists of relevant articles ." ], [ "moreover , the emergency of simultaneous hybrid procedures in especially designed multipurpose operating rooms combining the potential of catheter - based procedures and cardiac surgery will reduce the unnecessary costs incurred by staged hcr procedures [ 12 , 25 ] .", "lastly , more experience with minimally invasive cardiac surgery will shorten operative times , which might help reduce total healthcare costs .", "furthermore , the opportunity for quality control of the lita to lad bypass graft and anastomosis by a coronary angiogram is lost and , therefore , this strategy requires a reangiography [ 12 , 13 ] . these repeat control angiograms increase overall healthcare costs unnecessarily and decrease cost effectiveness . ", "three hcr strategies can be distinguished : ( i ) performing pci first , followed by lita to lad bypass grafting or ( ii ) vice versa ; ( iii ) combining lita to lad bypass grafting and pci in the same setting in a hybrid operative suite . in the included studies , staged hcr procedures ( i and ii ) were applied much more frequently than simultaneous procedures ( iii ) . in a", "however , failure of pci leading to emergency conventional cabg has become extremely rare with decreasing incidence since the introduction of coronary artery stenting [ 12 , 20 , 2932 ] .", "lita to lad bypass grafting in a minimally invasive fashion requires single - lung ventilation and chest cavity insufflation ." ], [ "this review is the largest and most comprehensive report to date comparing the clinical outcomes of patients who underwent either hybrid coronary revascularization or conventional on- or off - pump cabg for multivessel coronary artery disease .", "therefore , the different surgical techniques for lita to lad bypass grafting in the hcr procedure should be integrated in these large , multicenter hcr studies in order to determine the best way of lita to lad bypass grafting in hcr .", "three principal findings were revealed as follows : ( 1 ) hybrid treated patients showed a significantly faster recovery with lower prbc transfusion requirements and less in - hospital major adverse cardiac and cerebrovascular events than patients treated by on- or off - pump cabg ; ( 2 ) staged procedures were associated with considerable period of times between both procedures , leaving patients incompletely revascularized and in theory at risk for cardiovascular events for a considerable length of time ; and ( 3 ) the invasiveness of surgical lita to lad bypass grafting appeared to influence the clinical outcome , with higher macce and 30-day mortality rates in patients treated by more invasive surgical techniques using cpb and/or median sternotomy . as with any review , this report shares the limitations of the original studies .", "the first prospective , randomized pilot trial to compare hcr with conventional cabg in patients with multivessel coronary artery disease has been started ." ], [ "the large variability in hcr techniques makes it difficult to draw firm conclusions from the currently available evidence , but hcr appears to be a promising and cost - effective alternative for cabg in the treatment of multivessel coronary artery disease in a selected patient population .", "the hcr procedure was associated with short hospital stays ( including icu stay and intubation time ) , low macce and 30-day mortality rates , low prbc transfusion requirements and tvr , high postoperative lita patency rates , and high survival rates .", "these promising early outcomes warrant further research with larger sample size , multicenter rcts to determine the definite place of hcr in the current therapeutic armamentarium against coronary artery disease . until then", ", this review justifies the continued use of the hybrid approach , but careful patient selection and close cooperation between cardiac surgeons and interventional cardiologists will determine the clinical outcomes to a significant extent ." ] ]

[ [ "india is one of the ten countries , along with china , democratic republic of congo , pakistan , nigeria , bangladesh , ethiopia , indonesia , afghanistan , and tanzania , that account for more than 65% of all intrapartum related neonatal deaths . despite the recognition of neonatal survival as a key to child survival , poor progress in neonatal survival in india poses concern regarding attainment of the fourth millennium development goal ( mdg ) target , that is , to reduce under-5 child mortality by two - thirds by 2015 .", "globally four million deaths occur every year in the first month of life . almost all", "( 99% ) neonatal deaths arise in low - income and middle - income countries [ 1 , 2 ] . in india alone , around one million babies die each year before they complete their first month of life , contributing to one - fourth of the global burden [ 1 , 3 ] .", "the neonatal mortality rate in india was 32 per 1000 live births in the year 2010 , a high rate that has not declined much in the last decade [ 4 , 5 ] .", "the common causes of neonatal deaths in india include infections , birth asphyxia , and prematurity which contribute to 32.8% , 22.3% , and 16.8% of the total neonatal deaths , respectively [ 7 , 8 ] ." ], [ "similarly , in case of health worker ( male ) , there was a shortfall of 64.1% of the requirement . in case of health assistant ( female ) , the shortfall was 31.9% and that of health assistant ( male ) was 44% . the lack of qualified child care specialists results in a majority of rural households receiving care for their ill babies from private providers , many of whom are less than fully qualified .", "the condition of 4535 community health centers supposed to provide specialized medical care is even more appalling . as compared to requirements for an existing infrastructure , there was a shortfall of 62.6% of specialists at the chcs , 55.2% of obstetricians and gynecologists and 69.5% of pediatricians . according to the dlhs", " facility survey ( 2003 ) , healthcare facilities with newborn care staff and a medical officer trained in newborn care were 59% , 45.0% , and 34% at district hospital , first referral units ( frus ) and chcs , respectively .", "rural public health facilities across the country are having a difficult time attracting , retaining , and ensuring regular presence of highly trained medical personnel especially the gynecologists and pediatricians that are epochal in ensuring and promoting newborn health .", "as on march 2010 , the overall shortfall in the posts of health worker ( female)/auxiliary nurse midwife ( anm ) was 8.8% of the total requirement .", "these findings underscore the critical condition of the public health facilities that are meant to cater to the health problems of the newborns in rural india ." ], [ "the government of india has launched various initiatives envisaging a high priority action with regard to neonatal health . under national rural health mission ( nrhm ) , accredited social health activists ( ashas )", "a safe motherhood intervention named janani suraksha yojana ( jsy ) has been implemented under the nrhm to increase the institutional delivery rates and provide skilled care at birth for the newborn . under the reproductive and child health program ( rch - ii ) , the quality and reach of antenatal care is planned to be expanded and home - based newborn care using integrated management of neonatal and childhood illness ( imnci ) protocols is envisaged . ", "are being deployed and assigned the responsibility to create awareness in the community regarding maternal and child health issues .", "they are further expected to mobilize the community and help them in accessing healthcare services .", "neonatal health is seemingly one of the priority issues in the agenda of the government which gets reflected in the various programs devised and implemented ." ], [ "the main obstacles to improving newborn survival are that many babies are born at home without being attended by skilled personnel , faulty home - based newborn care practices are widespread , lack of awareness among care givers limits care - seeking for neonatal illness and even if that is taken care of , lack of trained health workforce adds to the problem .", "both of these are feasible and hold the promise to yield positive results but the real challenge lies in their reproduction and sustainment at the national level .", "this deficiency in skilled manpower undermines the initiatives by the government to improve neonatal health .", "there are broadly two ways of doing so , either bring the health system closer to the neonate or bring the neonate closer to the health system .", "another set of dilemma exists in bringing the neonates and the health system closer to each other ." ], [ "interventions in education and financial incentives along with professional support probably have the potential to ease out the problem , as had been seen in rural australia where the gprip continuing medical education grants and locum grants designed to assist rural general practitioners to maintain and increase their skills in areas relevant to rural practice helped in their retention in rural areas .", "other key initiatives could include establishing rural doctor networks , mentorship programmes , and giving rural practitioners preference in admissions in specialty programs .", "bolivia 's warmi program where the key highlight was participatory planning at the community level , with an emphasis on women 's participation to identify obstetric and perinatal health problems and their potential solutions . as a result of the intervention ,", "neonatal care in rural india is largely provided by a large number of unqualified healthcare providers [ 6971 ] .", "recruiting trained doctors by all means is one of the essential components towards providing quality maternal and neonatal care services .", "rural healthcare is provided by village doctors who are trained in preventive and curative medicine of both traditional chinese and allopathic schools .", "successful examples of improving maternal and neonatal health through public private partnerships have been documented in the literature [ 9598 ] ." ], [ "other options such as training of local rural healthcare providers and traditional midwives , promoting home - based newborn care , creating community awareness and community mobilization along with strengthening public - private partnerships should be explored further , as evidence generated from previous studies and large scale projects support these strategies as a way to improve neonatal health .", "more research should be directed towards upcoming innovations such as m - health in order to exploit the potential they offer in terms of enhancing the quality of care .", "much of the problem lies in the nonavailability of trained manpower and this in turn influences the quality of care the neonates receive .", "bringing qualified health professionals to rural , remote , and underserved areas is a challenging task which needs to be addressed urgently to avert neonatal deaths .", "to conclude , the neonatal mortality rate in india is still high and skewed towards rural areas ." ], [ "while the focus should be on devising strategies to recruit and retain trained manpower in rural areas , alternative strategies such as community mobilization , upscaling of home - based newborn care , imparting training and subsequent involvement of local rural healthcare providers and midwives should be attempted as well .", "more research is required to reveal the potential that innovations such as m - health , telemedicine , and public - private partnership hold in context to improving the quality of care in rural india ." ] ]

[ [ "here we report the first pediatric case of liver transplantation for the treatment of acute liver failure caused by vancomycin - induced dress syndrome in korea .", "the hypersensitivity syndrome , described as drug rash with eosinophilia and systemic symptoms ( dress ) syndrome is a severe , acute , drug reaction , defined by the presence of fever , cutaneous eruption , and systemic findings including enlarged lymph nodes , hepatitis , or hematologic abnormalities with eosinophilia and atypical lymphocytes1,2 ) .", "this reaction can be life threatening , with a mortality rate of approximately 10% , most commonly secondary to liver failure1 ) .", "the syndrome can involve several sites , leading to findings such as pneumonitis , renal failure , myocarditis , thyroiditis , or neurologic symptoms , but the liver is the most commonly affected internal organ3 ) ." ], [ ", there has not been any definite recurrence of dress syndrome , with the exception of persistently elevated levels of liver enzymes and intermittent eosinophilia .", "the patient is currently suffering from iatrogenic cushing 's syndrome owing to the high dose of steroids administered to control her elevated levels of liver enzymes .", "the detailed care of preliver and postliver transplantation and care of acute liver failure in our program was described elsewhere4,5 ) .", "given the presence of aggravated hepatic encephalopathy , azotemia , and that the patient was refractory to medical treatments , she received a living - donor liver transplantation from her aunt on hospital day 9 ." ], [ "we here report a pediatric case of acute liver failure resulting from dress syndrome , which was treated by liver transplantation .", "most reported cases of dress syndrome show that a cure can be achieved by the immediate withdrawal of the causative agent and the administration of methylprednisolone6 ) ." ] ]

[ [ "we aimed to investigate the outcomes of crrt on tbi patients in whom arf developed after trauma , and to study relevant factors which influence patients survival .", "however , little has been reported about the treatment results of crrt on tbi patients with arf .", "therefore , renal replacement therapy is required for tbi patients with arf to decrease post - traumatic mortality . among treatment modalities for arf , continuous renal replacement therapy ( crrt )", "has shown to have a much lesser effect on intracranial pressure ( icp ) than intermittent hemodialysis ( ihd).6 ) additionally , some authors have reported that crrt have an effect on lowering icp.89 ) regarding hemodynamics , crrt can be a better treatment modality for arf compared to ihd in severe tbi patients .", "despite the implementation of clinical guidelines and improvements in the critical care of patients with traumatic brain injury ( tbi ) , the prognosis of patients with severe tbi has remained poor during the last decade.16 ) the mortality rate of severe tbi is known to be about 32% to 52% , and about 6% to 11% of patients become vegetative or are severely disabled.313 ) it has been reported that dysfunction of at least one non - neurologic organ system develop in about 89% of patients with severe tbi . among them ," ], [ "between april 2011 and june 2015 , 1,190 tbi patients were treated at our institution . among them , 29 patients underwent renal replacement therapy for arf .", "we investigated survival time of 29 tbi patients who underwent crrt and analyzed the relationship between survival time and the laboratory , clinical , and radiological factors .", "the mean initial gcs score was 9.2 ( range , 3 - 15 ) , and the mean iss was 24 ( range , 9 - 59 ) .", "the mean age at admission was 60.2 years ( range , 16 - 84 ) .", "we retrospectively reviewed the laboratory , clinical , and radiological data of those 29 patients .", "the median starting date of crrt was 3 days ( range , 0 - 34 ) after tbi ." ], [ "the mean initial gcs score was 9.2 ( range , 3 - 15 ) , and the mean iss was 24 ( range , 9 - 59 ) .", "between april 2011 and june 2015 , 1,190 tbi patients were treated at our institution . among them , 29 patients underwent renal replacement therapy for arf .", "the mean age at admission was 60.2 years ( range , 16 - 84 ) .", "injury severity score ( iss ) has six categories to head and neck , face , chest , abdomen or pelvic contents , extremities or pelvic girdle , and external .", "brain computed tomography ( ct ) scan showed epidural hematoma ( edh ) , subdural hematoma ( sdh ) , intracerebral hemorrhage ( ich ) , and traumatic subarachnoid hemorrhage ( t - sah ) in 5 , 25 , 7 , and 17 patients , respectively .", "eighteen out of 29 patients underwent surgical intervention for treatment of tbi ( table 1 ) .", "we retrospectively reviewed the laboratory , clinical , and radiological data of those 29 patients .", "initial glasgow coma scale ( gcs ) score was checked when the patient was arrived to the emergency room ." ], [ "all 29 patients had normal kidney function on admission . however , 3 patients had a past history of chronic kidney disease .", "crrt was started when the serum creatinine level increased to more than twice of the basal level , and the urine output decreased to less than 30 ml per hour despite hydration and diuretics .", "when the patients urine output decreased , we checked the serum creatinine level and calculated the glomerular filtration rate .", "if the patients ' vital sign was stable , more than 100 ml / hour ( > 2400 ml / day ) of dialysis volume was removed .", "the median starting date of crrt was 3 days ( range , 0 - 34 ) after tbi ." ], [ "we investigated survival time of 29 tbi patients who underwent crrt and analyzed the relationship between survival time and the laboratory , clinical , and radiological factors .", "survival factors were categorized as follows ; age ( 65 vs. < 65 ) , 24-hours urine output ( 500 ml vs. < 500 ml ) before receiving crrt , iss ( < 25 vs. 25 ) , the presence of sdh , initial gcs score ( < 9 vs. 9 ) , pupil size at admission ( isocoria vs. anisocoria ) , cranial surgery ( yes vs. no ) , and intracranial hemorrhage ( edh , sdh , ich , t - sah absent vs. present ) . statistical analysis was performed using spss version 12.0 ( spss inc . ,", "kaplan - meier analysis was used and survival outcome was compared using the log - rank sum test for categorical variables ." ], [ "the actuarial median survival time of the 29 patients was 163 days after trauma ( range , 3 - 317 ) . among the 29 , 22 patients died with a median survival time of 8 days ( range , 3 - 55 ) ( figure 1a ) .", "the causes of death were tbi - related in 8 , sepsis due to pneumonia or acute respiratory distress syndrome ( ards ) in 4 , and multi - organ failure in 10 . among the various factors related to survival , 24-hr urine output before receiving crrt ( 500 ml vs. < 500 ml ) ( figure 1b ) , the presence of sdh ( figure 1c ) , and iss ( < 25 vs. 25 ) were significant after univariate analysis ( figure 1d , table 2 ) .", "median survival time was 10 days ( range , 3 - 136 ) when the patients urine output was less than 500 ml per day before receiving crrt , whereas more than half of the patients survived when the urine output was 500 ml per day or more ( p=0.015 ) .", "of the nine patients who had a 24-hours urine output of more than 500 ml per day before receiving crrt , 4 ( 44.4% ) patients died ( tbi - related brain herniation in 1 , multi - organ failure in 3 ) , with a median survival time of 146 days ( range , 4 - 317 ) .", "in multivariate analysis , only 24-hours urine output before receiving crrt ( 500 ml vs. < 500 ml ) remained as a significant factor ( p=0.026 ) ( table 2 ) ." ], [ "the actuarial median survival time of the 29 patients was 163 days after trauma ( range , 3 - 317 ) . among the 29 , 22 patients died with a median survival time of 8 days ( range , 3 - 55 ) ( figure 1a ) .", "the causes of death were tbi - related in 8 , sepsis due to pneumonia or acute respiratory distress syndrome ( ards ) in 4 , and multi - organ failure in 10 ." ], [ "median survival time was 10 days ( range , 3 - 136 ) when the patients urine output was less than 500 ml per day before receiving crrt , whereas more than half of the patients survived when the urine output was 500 ml per day or more ( p=0.015 ) .", "of the nine patients who had a 24-hours urine output of more than 500 ml per day before receiving crrt , 4 ( 44.4% ) patients died ( tbi - related brain herniation in 1 , multi - organ failure in 3 ) , with a median survival time of 146 days ( range , 4 - 317 ) .", "among the various factors related to survival , 24-hr urine output before receiving crrt ( 500 ml vs. < 500 ml ) ( figure 1b ) , the presence of sdh ( figure 1c ) , and iss ( < 25 vs. 25 ) were significant after univariate analysis ( figure 1d , table 2 ) .", "in multivariate analysis , only 24-hours urine output before receiving crrt ( 500 ml vs. < 500 ml ) remained as a significant factor ( p=0.026 ) ( table 2 ) .", "of the 20 patients who had a 24-hours urine output of less than 500 ml per day before receiving crrt , 18 ( 90.0% ) patients died ( tbi - related brain herniation in 7 , multi - organ failure in 11 ) , with a median survival time of 10 days ( range , 3 - 136 days ) ( figure 1b ) . for the patient with sdh ," ], [ "increased circulating cytokines can lead to disruption of the bbb , allowing increased access to cytotoxic inflammatory cells , cytokines , complement , amino acids , and organic osmolytes.14 ) therefore , it has been reported that tbi patients with arf have a higher incidence of poor outcome when compared with tbi patients without renal dysfunction.12 ) renal replacement therapy for arf in the patient with tbi is challenging , because conventional ihd is known to lead to an increase in brain water content , even in non - tbi patients undergoing regular hemodialysis.5 ) compared to standard ihd , crrt has been shown to result in greater intracranial stability.615 ) during treatment with crrt , changes in osmolality and changes of urea and bicarbonate levels were much less than those during ihd.5 ) this intracranial stability can be achieved by improved cardiovascular stability , because various modes of crrt can be selected according to cardiovascular volume status.4 ) therefore , it can be stated that crrt has many advantages over conventional ihd in the treatment of arf for patients with tbi .", "our result suggests that starting crrt in the early stage of arf is required to improve the survival rate of tbi patients who have worse outcomes compared to those without post - traumatic arf .", "further studies with a prospective design , many more cases , and control group with conventional ihd are necessary to prove the beneficial therapeutic effects of crrt compared to conventional ihd , and the best timing of initiation of crrt in the tbi patients with post - traumatic arf .", "however , to the best of our knowledge , this is the first analysis of outcomes of crrt in tbi patients with post - traumatic arf .", "tbi patients are often exposed to multiple trauma , sepsis , and many nephrotoxic drugs ." ], [ "according to our results , we suggest that early intervention with crrt before urine output is reduced to less than 500 ml per day may be beneficial in the treatment of tbi patients with impending arf . to define the therapeutic advantages of early crrt in the tbi patients with arf , a well - designed and controlled study with more cases" ] ]

[ [ "the aim of our study was to assess the tlr3 , tlr7 , and tlr9 expression on peripheral blood mononuclear cells ( pbmcs ) , including cd3 t lymphocytes and their cd4 and cd8 subpopulations , and cd19 b lymphocytes , in patients with sle , compared to healthy controls .", "the original results of this study serve as the first presentation of a simultaneous analysis of the relationship between the expression of the studied tlrs and disease activity , the degree of organ damage , several clinical and laboratory parameters , and the influence of immunosuppressive treatment .", "moreover , a correlation between the expression of tlrs and gender as well as pre- and postmenopausal period was evaluated .", "systemic lupus erythematosus ( sle ) is an autoimmune disease of connective tissue involving multiple organs .", "causes the opposite effect , leading to a clinical improvement being observed in animal sle models ." ], [ "representative dot plots from flow cytometry measurements of tlr3 and tlr9 expression on t- and b - cells in patients and healthy controls ( panel b ) are presented in figure 1(a ) .", "representative dot plots from flow cytometry measurements of tlr7 expression on b - cells in patients and healthy controls are presented in figure 1(b ) . for measurable characteristics ,", "thirty - five sle patients , diagnosed as having met at least 4 criteria according to the acr , were included in the study .", "disease activity was assessed according to the slam ( systemic lupus activity measure ) scale .", "organ damage was then assessed with the slicc / acr ( systematic lupus international collaborating clinics / american college of rheumatology ) damage index .", "all of the patients had been treated at the department of dermatology and venereology , medical university of lodz and did not present symptoms of active infection or neoplastic disease at the time of the study .", "patients who reached 10 and more points were diagnosed as having active sle . during the study ," ], [ "significantly higher percentages of tlr3- and tlr9-positive pbmcs and cd3 t lymphocytes , including those positive for cd4 and cd8 antigens , as well as cd19 b lymphocytes were observed among patients with sle , compared to healthy controls ( figures 2 and 3 ) . a higher percentage of cd19 b lymphocytes expressing tlr7 was found in patients with sle than in healthy subjects ( p < 0.006 ) ( figure 4 ) . with regard to pbmcs and both subpopulations of t lymphocytes , tlr7 expression did not differ between patients and healthy controls ( table 2 ) .", "a review of the clinical findings reveals that only patients with joint symptoms have lower tlr9-positive cd19 b lymphocyte counts , compared to subjects with no joint symptoms .", "no statistically significant correlation was observed between the expression of studied tlrs and immunosuppressive treatment .", "there were no significant correlations between the proportions of various cell subsets expressing the studied tlrs and disease activity ( table 2 ) .", "no statistically significant correlation was observed between the expression of any of the studied types of tlr among the given cell subpopulations and the degree of organ damage according to the slicc / arc damage index ." ], [ ", our results suggest that tlrs exert an influence on sle development and describe the potential roles played by tlrs in the involvement of specific organs in this disease .", "our findings warrant further studies on tlr expression in t lymphocytes from patients with sle , as they may lead to a better understanding of the complex interactions between innate and acquired immunity in the pathogenesis of sle .", "despite intensive research in many centres , the pathogenesis of sle remains poorly understood , and hence , the condition lacks targeted therapy . however , the discovery of tlrs in humans opened a new field in the studies of lupus , and our study of tlr3 , tlr7 , and tlr9 confirms their potential influence on the disease .", "even so , more targeted studies concerning the biology and function of tlrs are warranted and may lead to the development of a new class of drugs .", "higher expression of tlr9 has been shown in sle patients , compared to healthy individuals , which is consistent with our findings . however , the results of studies concerning tlr3 and tlr7 expression are inconsistent ." ] ]

[ [ "nr is an atypical presentation of toxoplasmosis infection , and such cases are quite rare .", "neuroretinitis ( nr ) is considered to be an inflammatory condition which is characterized by optic disc edema and , as a result , formation of a macular star figure ." ], [ "a 13-year - old girl presented with painless subacute visual loss in her right eye for a week at khatam - al - anbia eye hospital in mashhad , iran ." ], [ "although toxoplasmosis nr is rare , it should be considered in the differential diagnoses of nr ." ], [ "serologic tests for most cases may include the fluorescent treponemal antibody absorption test ( fta - abs ) , cat scratch titers ( bartonella species ) , and a tuberculosis skin test ( purified protein derivative , or ppd ) ( 1 ) . in this study , we present a case of unilateral neuroretinitis in which the serology result was apparently negative for acute infection of toxoplasmosis ( negative igm titer for toxoplasmosis , but positive for igg ) .", "based on anti - toxoplasma treatment that was administered for the positive igg levels , the condition responded well with near optimal visual recovery .", "neuroretinitis ( nr ) is considered an inflammatory condition which is characterized by optic disc edema and , as a result , formation of a macular star figure ( 1 ) .", "however , there are other infectious etiologies of neuroretinitis , including rubeola , toxoplasmosis , herpes simplex , varicella , tuberculosis , lyme disease , leptospirosis , syphilis , various fungi , and multiple viral illnesses ( 1 ) ." ], [ "a 13-year - old girl was referred to the ophthalmic emergency department of khatam - al - anbia eye hospital , mashhad , iran , which is affiliated with mashhad university of medical sciences ( mums ) , in may of 2013 with painless subacute visual loss in her right eye for one week .", "the investigation of the right fundus revealed optic disc swelling , macular star lipid ( hard exudates ) deposition , and peripapillary vascular sheathing ( figure 1 ) .", "an examination of the anterior segment demonstrated 2 + cells in the anterior chamber ( a / c ) and 1 + vitreous reaction with normal intraocular pressure ( iop ) in the right eye .", "gradually , over the next two months , the patient s visual acuity improved to 9/10 and the optic disc swelling and macular exudates resolved ( figure 2 ) .", "moreover , the patient had a grade 2 + relative afferent papillary defect ( rapd ) in the right eye ." ], [ "the clinical syndrome of idiopathic stellate maculopathy accompanied by optic nerve edema was first identified by leber in 1916 ( 5 ) . later on ,", "this case disclosed optic disc involvement and neuroretinitis owing to juxtapapillary chorioretinitis reactivation . in some cases ,", ". this case re - emphasizes the necessity of considering toxoplasmosis in the differential diagnosis of neuroretinitis .", "toxoplasmosic retinochoroiditis is rendered as one of the most frequent causes of posterior uveitis , specifically in young patients ( 6 ) .", "although toxoplasmosis neuroretinitis is rare , it should be still considered in any suspected case of neuroretinitis" ] ]

[ [ "we used bootstrap to compute ses of the indicators by resampling 1000 times the ensemble of replicate populations ( for the coefficient of variation and the temporal correlation ) or arrays ( for the spatial correlation ) .", "3b ) divided by the sample mean . because the local populations in our experiment were grown in a homogeneous environment , in principle they could all be treated as replicates . assuming the system is ergodic , the cv calculated over an ensemble of replicates can be interpreted either as spatial cv of many populations at one time point or temporal cv of a single population over many time points .", "4c ) may be due to the limited data points used in fitting or experimental errors . for both the half - point recovery length and the exponential recovery length , we used bootstrap to compute ses for the indicators by resampling the ensemble of steady - state profiles 100 times and fitting the average recovery profile .", "the position of half recovery can be defined as the midpoint between the equilibrium population density of the region of interest and the population density at the boundary .", "after the recovery profile stabilized , we tracked the population density profiles of at least 6 replicates over several days .", "we note that our definition of exponential recovery length is phenomenological , because : 1 ) the deviation is expected to be exponential only close enough to the equilibrium ; 2 ) at higher dilution factors the profile can deviate from an exponential form ( supplementary fig .", "the expectation of moran s coefficient is 1n1 in the absence of spatial correlation ; we used a modified estimator with an additional term 1n1 so that the expectation is 0 . in this case , the sample size n is the number of patches in an array : n=10 for connected populations ; n=5 for isolated populations . for detailed formula of the statistical indicators , see supplementary note 4 . in the analysis we ensured environmental homogeneity by removing a linear gradient of population density observed in connected populations", "the small gradient is presumably caused by some heterogeneity in experimental conditions ( temperature , dilution errors , etc . ) across the plate ." ], [ "were adopted , meaning that a population on the edge would have 75% of its cells remaining in the patch during the dispersal step . in the group of isolated populations ,", "the calibration between optical density and cell density was based on the previous characterization of this system . in the group of connected populations , for each dilution factor there were 4 replicate arrays each consisting of 10 patches .", "populations were connected by controlled dispersal between nearest neighbors ( dispersal rate d=0.5 , which is defined as the fraction of population going out of a patch ) . reflecting boundary conditions", "the dilution factor for the bad region ( 1 patch ) was 2500 ; the dilution factor for the good region ( 5 patches ) was varied as the environmental driver .", "the dilution factors for the data presented in fig . 2 are 500 , 1000 , 1200 , 1400 and 1600 . in the experiment to measure recovery length ,", "populations were connected by nearest - neighbor dispersal ( d=0.5 , reflecting boundary conditions ) .", "the experiment was performed in a similar spatial setting except that there was no dispersal ( d=0 ) ; for each dilution factor there were 4 arrays each consisting of 5 patches , thus a total of 20 replicate populations isolated from each other .", "we grew the budding yeast saccharomyces cerevisiae in 200 l batch culture on bd falcon 96-well microtest plates at 30.7 c ( 0.2c , standard deviation ) using synthetic media ( yeast nitrogen bases + nitrogen , complete supplement mixture ) supplemented with 2% sucrose ." ], [ "in the analysis we ensured environmental homogeneity by removing a linear gradient of population density observed in connected populations .", "we used bootstrap to compute ses of the indicators by resampling 1000 times the ensemble of replicate populations ( for the coefficient of variation and the temporal correlation ) or arrays ( for the spatial correlation ) .", "assuming the system is ergodic , the cv calculated over an ensemble of replicates can be interpreted either as spatial cv of many populations at one time point or temporal cv of a single population over many time points .", "the small gradient is presumably caused by some heterogeneity in experimental conditions ( temperature , dilution errors , etc . ) across the plate .", "removing gradient - type spatial heterogeneity before statistical analysis is similar to the detrending procedure commonly used in time - series analysis ; it prevents spurious signals such as positive spatial correlation ( supplementary fig .", "the expectation of moran s coefficient is 1n1 in the absence of spatial correlation ; we used a modified estimator with an additional term 1n1 so that the expectation is 0 . in this case , the sample size n is the number of patches in an array : n=10 for connected populations ; n=5 for isolated populations . for detailed formula of the statistical indicators , see supplementary note 4 .", "the temporal correlation , defined as the lag-1 autocorrelation , was estimated by the pearson s correlation coefficient between the population densities at subsequent days . to correct for negative bias in small samples" ], [ ", the position of half recovery can be defined as the midpoint between the equilibrium population density of the region of interest and the population density at the boundary .", "we note that our definition of exponential recovery length is phenomenological , because : 1 ) the deviation is expected to be exponential only close enough to the equilibrium ; 2 ) at higher dilution factors the profile can deviate from an exponential form ( supplementary fig .", "4c ) may be due to the limited data points used in fitting or experimental errors . for both the half - point recovery length and the exponential recovery length , we used bootstrap to compute ses for the indicators by resampling the ensemble of steady - state profiles 100 times and fitting the average recovery profile", "after the recovery profile stabilized , we tracked the population density profiles of at least 6 replicates over several days .", "the exponential recovery length was estimated by fitting an exponential function with three parameters c1 exp(x / l ) + c2 to the recovery profile n(x ) ." ], [] ]

[ [ "however , the reliability of the classification has not been assessed . as such , the following study aimed to test the classification 's reliability .", "the prediction of a patient 's growth potential is of clinical significance because it determines the optimal timing of starting or stopping bracing and the timing of growth - guidance surgery with an expandable prosthesis.1 \n 2 \n 3 \n 4 many clinical and radiologic methods are available to predict a patient 's growth potential including the age at menarche , difference in body height growth and arm span , risser sign , and tanner and whitehouse ( tw3 ) digital skeletal age.5 \n 6 \n 7 \n 8 however , most of these measures have disadvantages in the current clinical practice.9 clinical measurements of standing height and arm span require serial measurements to determine growth trends , and its retrospective nature thus likely misses the period of peak growth spurt ." ], [ "a prospective radiographic study assessing patients with adolescent idiopathic scoliosis ( ais ) undergoing bracing during the month of july 2014 was performed to assess the reliability of the dru classification.19 ethics approval was obtained from our institutional review board .", "the study was performed at the duchess of kent children 's hospital , pokfulam , hong kong , a tertiary referral center for spinal disorders . for the dru classification to be practical clinically", "the reliability assessment was based on intraclass correlation ( icc ) , which was an appropriate statistical tool for this analysis.20 icc could be interpreted based on the following values : 0 to 0.29 indicated poor agreement ; 0.30 to 0.49 indicated fair agreement ; 0.50 to 0.69 indicated moderate agreement ; 0.70 to 0.80 indicated strong agreement ; and > 0.80 indicated almost perfect agreement.21 \n 22 the 95% confidence interval ( ci ) bounds were assessed for precision . a p value of < 0.05 was considered significant .", "the follow - up left - hand radiographs during the study month were obtained in all subjects , and data was extracted regarding the age at which the radiograph was taken and the sex of the patient .", "there was no discussion between the two examiners about how to classify each grade prior to the initiation or during the study .", "in addition , the aim of this classification was to correctly identify patients in the peak growth spurt so that timely interventions can be applied .", "thus , choosing braced patients would likely encompass a larger range of grades and avoid reliability assessment of only a certain age group or dru grade .", ", the reliability testing should be based on a wide range of patient ages , as commonly seen in our clinics ." ], [ "the reliability assessment was based on intraclass correlation ( icc ) , which was an appropriate statistical tool for this analysis.20 icc could be interpreted based on the following values : 0 to 0.29 indicated poor agreement ; 0.30 to 0.49 indicated fair agreement ; 0.50 to 0.69 indicated moderate agreement ; 0.70 to 0.80 indicated strong agreement ; and > 0.80 indicated almost perfect agreement.21 \n 22 the 95% confidence interval ( ci ) bounds were assessed for precision . a p value of < 0.05 was considered significant .", "spss version 20 ( chicago , illinois , united states ) was utilized to perform the statistical analysis .", "all data was coded and entered on a spreadsheet and was blinded to the examiners until the end of reliability measurements ." ], [ "one hundred sixty - one subjects ( 124 females and 37 males ) satisfied our inclusion criteria and were recruited for this study .", "was as follows : for the radius , there were 28 one - grade disagreements ( 17.3% ) and 5 two - grade disagreements ( 3.1% ) .", "for the ulna , there were 42 one - grade disagreements ( 25.9% ) and 2 two - grade disagreements ( 1.2% ) .", "for the ulna , there were 40 one - grade disagreements ( 24.7% ) and 5 two - grade disagreements ( 3.1% ) .", "the intraobserver disagreement for k.d .- k.l . was as follows : for the radius , there were 26 one - grade disagreements ( 16.0% ) and 4 two - grade disagreements ( 2.5% ) .", ", there were 18 one - grade disagreements ( 11.1% ) and 1 two - grade disagreement ( 0.6% ) . for the ulna , there were 39 one - grade disagreements ( 24.1% ) and 1 two - grade disagreement ( 0.6% ) .", "the mean age was 13.3 ( standard deviation : 1.5 ; range : 8 to 18 ) .", "was icc = 0.93 ( 95% ci : 0.91 to 0.95 ) for the radius and icc = 0.95 ( 95% ci : 0.930.96 ) for the ulna ; for k.d .- k.l . , icc = 0.94 ( 95% ci : 0.91 to 0.95 ) for the radius and icc = 0.95 ( 95% ci : 0.93 to 0.96 ) for the ulna ." ], [ "for the radius , there were 18 one - grade disagreements ( 11.1% ) and 1 two - grade disagreement ( 0.6% ) . for the ulna , there were 39 one - grade disagreements ( 24.1% ) and 1 two - grade disagreement ( 0.6% ) .", "the intraobserver disagreement for j.p.y.c . was as follows : for the radius , there were 28 one - grade disagreements ( 17.3% ) and 5 two - grade disagreements ( 3.1% ) .", "the intraobserver disagreement for k.d .- k.l . was as follows : for the radius , there were 26 one - grade disagreements ( 16.0% ) and 4 two - grade disagreements ( 2.5% ) .", "for the ulna , there were 42 one - grade disagreements ( 25.9% ) and 2 two - grade disagreements ( 1.2% ) .", "for the ulna , there were 40 one - grade disagreements ( 24.7% ) and 5 two - grade disagreements ( 3.1% ) ." ], [ "from this study , we found that the dru classification had excellent reliability among a wide range of radius and ulna grades.19 although we did not have patients young enough to present with radius stages r1 to r4 , interventions for ais such as bracing are only applicable during the peak growth spurt .", "the dru has been shown to be strongly associated with the peak growth phase and growth cessation,19 which can help clinicians decide between bracing and surgery . the results from this study suggested that the dru classification was a reliable method to assess skeletal growth .", "in addition , it can be used to help decide the appropriate timing for initiation and cessation of bracing , when to use growth guidance surgery , and when to recommend fusion . by more accurately predicting a child 's remaining growth potential", ", prospective studies are being developed to apply this classification scheme on patients with ais to determine its sensitivity and specificity in identifying the peak growth spurt , predicting curve deterioration , as well as detecting skeletal maturity ." ] ]

[ [ "the results demonstrate that a meaningful evaluation of the efficacy of , for example , vaccine candidates and/or chemotherapeutically interesting compounds against experimental infection with n. caninum in mice requires standardization with regard to the mouse strains used for such experiments .", "however , since the immune response is not capable of controlling the parasite , the risk of transplacental transmission of n. caninum is relatively high .", "\n neospora caninum is an apicomplexan protozoan , infecting a large range of mammals . in cattle ,", "several studies focussing on the specific immune response to n. caninum in cattle have shown that the time of gestation is important with regard to the outcome of the infection .", "a humoral immune response is therefore not sufficient to clear a n. caninum infection . for more efficient protection against intracellular pathogens such as n. caninum" ], [ "sera of nave swiss outbred mice ( charles river , sulzfeld , germany ) were used as a negative control . as a positive control for igg1 and igg2a detection , sera of balb / c mice vaccinated with the chimeric antigen r - mic3 - 1 and challenged with n. caninum ( nc-1 isolate )", "serum antibody levels were analysed using a commercially available elisa kit based on antigens of n. caninum ( idexx neospora ab test , idexx laboratories , westbrook , usa ) according to the instructions of the manufacturer . on each plate , sera were tested in 2log titrations , and negative and positive sera were tested in octaploid .", "the proportion of animals with clinical signs , proportion of animals with brain lesions and data on n. caninum - dna - positive animals were organized in a contingency table and compared by a chi - square test .", "neospora - specific quantitative real - time pcr to determine the number of tachyzoites that has reached the cerebral tissue was performed as previously described [ 2 , 3 , 15 ]", ". dna extraction from brain tissue was performed using the dneasy blood & tissue kit ( qiagen , hilden , germany ) according to the manufacturer recommendations . the dna concentration in each sample", "latest at day 34 postinfection ( pi ) , surviving mice were sacrificed by cervical dislocation and brains and spleens were harvested . for each mouse ,", "mice were then closely monitored daily for neosporosis disease symptoms according to a clinical scoring system that included hunched back , rough hair coat , impaired movement , and spinning . for each feature" ], [ "experimental infection of balb / c mice with 1 10 or 5 10 tachyzoites resulted in high igg2a and igg1 serum levels , indicating the presence of a mixed cellular and humoral immune response ( table 1 ) .", "the production of igg1-type antibodies is primarily induced by a humoral immune response , whereas igg2a subclasses indicate the involvement of a cellular immune response .", "the surviving balb / c mice infected with 1 10 tachyzoites ( n = 5 ) and cba / ca mice infected with 5 10 tachyzoites ( n = 5 ) were challenged again with 25 10 n. caninum tachyzoites at day 34 . however , they all succumbed to infection within 24 hrs , indicating that they had not built up any form of protective immunity . in order to obtain information on the type of immune response induced by n. caninum infection ,", "challenge of balb / c mice with 5 10 tachyzoites resulted in high cerebral parasite load in all mice , and brain lesions were detected upon histopathological inspection in four out of five mice ." ], [ "significant differences in the responses to n. caninum infection in inbred and outbred mice have been demonstrated previously , and these differences have been postulated to be due to varying abilities to present n. caninum antigens on their mhc molecules .", "in this study , we compared the capacities of three inbred mouse strains expressing different mhc - i molecules to cope with a n. caninum infection .", "when using mouse models to investigate the outcome and immunological parameters of infection , the selection of the n. caninum isolate as well as inoculum doses are important variables that will influence the results .", "the present study showed high variations in morbidity and mortality in the three inbred mouse strains balb / c , cba / ca , and c57bl/6 after inoculation with different numbers of n. caninum ( nc - liv ) tachyzoites , demonstrating that the choice of mouse strain plays a crucial role for the assessment of experimental infections and agents that could potentially interfere therein . while balb / c mice did not suffer from clinical signs of neosporosis after a challenge dose of 1 10 n. caninum tachyzoites , infection with 5 10 tachyzoites resulted in severe clinical symptoms starting at day 20 pi .", "in contrast , only limited research has been performed using cba / ca mice as a model to investigate the immune responses against n. caninum infection ." ] ]

[ [], [ "halobacillus massiliensis marseille - p3554 ( lt671593 ) , lentibacillus massiliensis marseille - p3089 ( lt598549 ) , oceanobacillus senegalensis marseille - p3587 ( lt714172 ) oceanobacillus timonensis marseille - p3532 ( lt671597 ) , virgibacillus dakarensis marseille - p3469 ( lt631544 ) and virgibacillus marseillensis marseille - p3610 ( lt714170 ) .", "the 16s r rna gene sequences were deposited in genbank under the following accession numbers : bacillus dakarensis marseille - p3515 ( lt671589 ) , bacillus sinesaloumensis marseille - p3516 ( lt671591 ) , " ], [ "the strains were deposited in the collection de souches de lunit des rickettsies ( csur , wdcm 875 ) under numbers bacillus dakarensis marseille - p3515 ( p3515 ) , bacillus sinesaloumensis marseille - p3516 ( p3516 ) , gracilibacillus timonensis marseille - p2481 ( p2248 ) , halobacillus massiliensis p3554 ( p3354 ) , lentibacillus massiliensis marseille - p3089 ( p3089 ) ,", "virgibacillus dakarensis marseille - p3469 ( p3469 ) and virgibacillus marseillensis marseille - p3610 ( p3610 ) ." ] ]

[ [ "hence , the aim of this study was to evaluate the role of nc and nhtr as independent predictors of mets and its components among asian indians as compared to traditional anthropometric indices ( bmi , wc , and whtr ) .", "furthermore , the predictive potential of nc based indices for predicting mets and its components , as compared to the traditional anthropometric indices ( bmi , wc , and whtr ) among indians are not known .", "few studies have suggested that subcutaneous adipose tissue in the upper body distribution ( upper body obesity ) , to have an independent role in predicting cardiovascular morbidity .", "neck circumference ( nc ) has been validated to be a simple measure of upper body subcutaneous fat deposition and being a predictor of cardiovascular risk factors .", "cardiovascular disease is the predominant cause for mortality in patients with type-2 diabetes mellitus , accounting for 5060% of deaths .", "specific challenges associated with diabetes in india , the single most important contributor to cardiovascular morbidity and mortality , is the high prevalence of diabetes ( 9% ) and also prediabetes ( 1214% ) , young age of disease onset , with significantly higher rates of disease progression ( prediabetes to diabetes conversion rate in india , china , finland , and the usa being ( 1418% , 11% , 6% , and 2.5% , respectively ) . hence , there is an urgent need of easy to measure anthropometric marker , specific to the indian population , which is a good marker for early diagnosis of this high - risk cohort of individuals , who are predisposed to mets , diabetes , and cardiovascular morbidity ." ], [ "the prevalence of mets in india has been reported to be 31.6% . keeping a power of 80% and type - i error at 5% ,", "it was calculated that we needed to evaluate at least 235 individuals with mets in our study .", "receiver operating characteristic ( roc ) analyses were performed to assess the accuracy of the anthropometric parameters as diagnostic tests for detecting mets and determine optimal sex - specific nc cut - offs in relation to mets .", "screening of apparently healthy individuals that included family members of patients with diabetes was done during these camps by either fasting blood glucose ( fbg ) if they came after an overnight fast , or a non - fbg using a glucometer ( accu - chek active ; roche , mumbai , india ) .", "the associations between metabolic risk factors and anthropometric parameters were assessed using partial correlation analysis .", "the presence of mets was ascertained using the modified national cholesterol education program adult treatment panel ( ncep atp ) iii criteria ( ethnic - specific cutoffs for wc viz . >" ], [ "receiver operating characteristic ( roc ) analyses were performed to assess the accuracy of the anthropometric parameters as diagnostic tests for detecting mets and determine optimal sex - specific nc cut - offs in relation to mets .", "anova with post hoc analysis and kruskal wallis nonparametric anova with dunn 's postcorrection were performed for normally and nonnormally distributed variables , respectively .", "the associations between metabolic risk factors and anthropometric parameters were assessed using partial correlation analysis .", "pearson 's or spearman 's correlation coefficient was calculated for normally and nonnormally distributed variables , respectively . for categorical data , frequencies , and percentages", "the youden index , defined as ( sensitivity + specificity)-1 was used to determine the optimal cut - off points .", "spss version 16 ( chicago , il , usa ) was used for statistical analysis ." ], [ "ckd : chronic kidney disease ; cld : chronic liver disease ; cva : cerebrovascular accident ; tia : transient ischemic attack ; cad : coronary artery disease baseline characteristics of the study population with regards to sex distribution and occurrence of metabolic syndrome ( n=451 ) males and females were divided into subgroups based on nc tertile [ table 2 ] . in", "a total of 867 individuals were screened of which 451 individual who fulfilled all inclusion and exclusion criteria , gave informed consent , and came for detailed anthropometric and biochemical evaluation were included in the study and analyzed [ figure 1 ] . in our study , 228 , 55 and 168 individuals were classified as having normoglycemia , prediabetes , and diabetes respectively as per fbg and hba1c values .", "both the sexes , individuals in the highest tertile of nc had significantly greater central obesity , significantly more likely to have bmi in the overweight and obese range , lower hdl - c and significantly higher occurrence of mets [ table 2 ] .", "among all the 4 anthropometric parameters evaluated , nhtr had the highest auc with regards to predicting mets , hypertension , hypertriglyceridemia , and low hdl - c in males [ table 5 ] . in females , wc had the highest auc with regards to predicting mets and hypertension , whereas nc had the highest auc with regards to predicting low hdl - c ." ], [ "our study demonstrated for the 1 time the reliability of nhtr as a predictor of mets and its components and highlighted that nhtr is perhaps an even better index than nc with regards to cardiovascular risk prediction .", "it may be said that our study reinforced the previous observation of nc being a good predictor of mets and other related cardiovascular risk factors in asian indians .", "nc has been demonstrated to be an index of upper body subcutaneous fat , with correlation with indices of obesity and individual cardiovascular risk factors . in a longitudinal follow - up study , it was shown that the change is nc correlated with changes in cardiovascular risk factors and that using wc alone was a simplification and did not account for all the changes in risk factors .", "wc a measure of abdominal subcutaneous and visceral fat traditionally has served as the standard index to identify patients with mets .", "nc had a strong positive correlation with traditional anthropometric indices of central obesity ( bmi and wc ) , which are also established predictors of cardiovascular risk ." ], [ "this study was funded by a research grant from research society of study of diabetes in india , west bengal chapter ." ], [] ]

[ [ "a woman who developed pityriasis rosea during her first trimester of pregnancy and who subsequently delivered a healthy baby with craniosynostosis is described , and observations of infants born to women who are diagnosed with pityriasis rosea during their gestation are summarized .", "pityriasis rosea is considered to be a benign cutaneous condition [ 14 ] . however , in the setting of pregnancy , adverse effects on the newborn may be observed .", "craniosynostosis is a congenital abnormality , which can occur as an isolated finding or as part of a syndrome with other associated features ." ], [ "a diagnosis of pityriasis rosea was established based on the appearance of the lesions and history .", "a diagnosis of inverse pityriasis rosea was established based on the clinical history and lesion morphology .", "a 28-year - old healthy woman presented at 10 weeks gestation with a skin rash ." ], [ "isolated craniosynostosis has not been observed in newborns of women who developed pityriasis rosea during their gestation .", "most of the women ( 66% , n=35 ) developed pityriasis rosea during the second trimester of gestation ( 1328 weeks ) .", "twenty - five women ages 24 to 34 ( median age 29)had no prior pregnancies . however , pityriasis rosea occurred during either the second ( 20 women ) or the third pregnancy ( 6 women ) for the other women .", "the interval between onset of pityriasis rosea in the wife after occurrence in the husband ranged from seven days to one year ( median : 2 months ) .", "the median number of weeks of pregnancy at the onset of pityriasis rosea was 19 .", "our patient s husband developed and cleared inverse pityriasis rosea two months prior to his wife developing classic pityriasis rosea .", "additional studies looking at the association between hsv-6 and hsv-7 dna and the occurrence of pityriasis rosea in pregnancy have also been performed . some of the studies found reactivation of hsv-6 during pregnancy . however , a positive correlation between viral infection and clinical features of pityriasis rosea was not established ." ], [ "some researchers noted that pityriasis rosea occurring earlier in pregnancy had a greater probability of resulting in adverse events for the fetus , including stillbirth , low gestational weight , hypotonia , and/or premature delivery .", "however , there are a similar number of reports of women who developed pityriasis rosea during their gestation and delivered normal newborns .", "however , the true incidence is not known , since gestational pityriasis rosea is not frequently reported .", "her son was carried to term and delivered at 40 weeks and 6 days with apgar scores , weight , and height in normal range .", "our patient developed pityriasis rosea during her first trimester beginning at 8 weeks gestation and lasting through 18 weeks .", "whether the presence of craniosynostosis was associated with our patient s development of pityriasis rosea during her pregnancy remains to be determined ." ] ]

[ [ "we describe 2 patients with bcs who were successfully diagnosed with endoscopic retrograde cholangio pancreatography ( ercp ) and one of whom was successfully treated endoscopically .", "bile cast syndrome ( bcs ) is a complication of orthotopic liver transplantation ( olt ) ." ], [ "subsequent to removal of the biliary cast , endoscopic treatment for the anastomotic stricture resulted in resolution of the stricture .", "balloon sweeps yielded a small amount of debris , but cholangiographic findings persisted that were concerning for filling defects or marked ductal irregularity in the region of the common hepatic duct and bifurcation .", "it appears to contain filling defects which retrospectively are related to presence of biliary cast material in the right and left main hepatic ducts . \n", "a tubular biliary cast , in the shape of the bile duct , was seen in the donor bile duct extending from the anastomosis into the intrahepatic ducts ." ], [ "balloon sweeps yielded a small amount of debris , but cholangiographic findings persisted that were concerning for filling defects or marked ductal irregularity in the region of the common hepatic duct and bifurcation .", "it appears to contain filling defects which retrospectively are related to presence of biliary cast material in the right and left main hepatic ducts . \n", "a tubular biliary cast , in the shape of the bile duct , was seen in the donor bile duct extending from the anastomosis into the intrahepatic ducts ." ], [ "a 58-year - old male with a history of hepatitis c and cirrhosis presented with fevers , chills , and a headache .", "subsequent to removal of the biliary cast , endoscopic treatment for the anastomotic stricture resulted in resolution of the stricture .", "cholangiogram prior to intervention shows diffuse stricturing of the left and right hepatic ductal system in patient 2 ." ], [ "percutaneous transhepatic choledocoscopy via a tract created with radiographic assistance is a novel approach used for management of bcs . when there is intrahepatic biliary system involvement , management becomes even more challenging .", "a combination of endoscopic interventions is considered including sphincterotomy , balloon and basket extraction , lithotripsy and stent placement . in one study ,", "microcirculatory dysfunction is also suggested , given the higher prevalence of renal failure and need for renal replacement therapy in patients with bcs 7 .", "success rates with endoscopic therapy for bcs have been reported to be 70 % recently 7 .", "percutaneous drainage has also been advocated , especially in the setting of cholangitis or with roux - en - y choledochojejunostomy ." ] ]

[ [ "we performed a gunderson conjunctival flap under local \n anesthesia ( la ) , which retracted and failed after one week . \n", ", we decided to use \n processed bp xenograft ( lyolemb ) supplied by national tissue \n bank , universiti sains malaysia after obtaining the consent of the \n patient .", "slit - lamp examination revealed a large central corneal perforation \n ( 4 5 mm ) with surrounding stromal thinning involving two- \n thirds of the cornea without any signs of infection . in order to maintain the shape of the eyeball and due to the \n problem of non - availability of donor cornea", "nine months follow - up \n showed a well - taken graft without any exposure / dehiscence and \n minimal inflammation [ figure 2 ] ." ], [ "processed bp is a tough lyophilised collagen sheet used \n as a surgical armamentarium in wrapping orbital implants.4,5 it renders the material antigenically inert and adds to its \n strength , pliability and longevity.5 it has been shown to be \n well tolerated with minimal inflammation in animal studies.4 \n although theoretic concerns about prion disease can be raised , \n no evidence of this problem has been reported from over \n 90,000 human implantations.6 devron reported no significant \n ophthalmic reactions due to this xenograft in his cases of orbital \n implants.7 at the national tissue bank , universiti sains malaysia , \n the procured pericardium sheet was washed using chemical \n agent ( sterile phosphate buffer at ph 7.4 ) and frozen to 40c . \n", "conjunctival flap is unlikely to seal large corneal perforations \n associated with corneal melting following chemical injury . \n", "its use in complicated ocular surface \n diseases such as large corneal perforation with corneal melting \n can be promising .", "efficacy of amt alone or with glue in treating small corneal \n perforation has been well established but found unable to \n promote corneal stability in patients with severe corneal \n thinning and therefore , an additional urgent tectonic procedure \n has to be undertaken.3 non - availability of donor cornea poses \n a considerable problem in some countries .", "its use needs to be further studied more \n extensively as an alternative graft material in large corneal \n perforations ." ] ]

[ [ "the desynchronization of central and peripheral circadian systems contributes to the decline in optimal functioning of bodily systems .", "it is increasingly evident that determining the source of age - related sleep / wake or circadian dysfunctions is rather complex .", "any one or a combination of these abnormalities may result in the decoupling of the circadian oscillators and the ensuing pathologies .", "the output from circadian and peripheral oscillators do not only influence the sleep / wake cycle , but regulates metabolism and reproduction ." ], [ "another source of sleep / wake changes can likely be attributed to age - related neuronal dysfunction in the arousal and sleep promoting areas of the brain .", "age - associated changes in the serotonergic system affect the function of respiratory motor output during sleep .", "it is likely with normal aging that changes in any neurotransmitter system affecting sleep vary across the brain .", "given these changes in the aging wake promoting neurotransmitter systems as well as wake maintaining systems , it is clear that therapies to alleviate or attenuate these changes need to be developed ." ], [ "amyotrophic lateral sclerosis is a complex disease of many subtypes with various genetic and environmental contributing factors .", "in many patients afflicted with neurodegenerative diseases the physical and mental consequences lead to sleep disorders ( table 1 ) .", "however , some research indicates that sleep disturbances may predict manifestation of neurodegenerative diseases ( postuma and montplaisir , 2009 ) .", "increases in the number of patients with neurodegenerative diseases may be related to or the result of a society that does not sleep .", "chronic sleep loss could lead to neuronal damage resulting in altered hypothalamic pituitary adrenal axis function , cognitive deficits and memory loss ." ], [ "normally the scn is coupled to peripheral oscillators , although studies have shown that scn control is not necessary for sustaining oscillatory activity . if signals from central oscillators reduce in strength due to age or neurodegeneration , other cues may entrain the peripheral oscillators ( weinert , 2005 ) . unmasking mechanisms within sleep", "understanding how the aging brain can compensate and remain plastic will be beneficial to focus on more effective treatments for sleep / wake and neurodegenerative disorders .", "although compensation and plasticity occurs to a lesser extent in older animals , a relatively high degree is preserved ( van someren et al . , 2002 ) .", "this may not always be advantageous as epigenetic methylation of circadian genes has been associated with dementia ( liu et al . , 2008 ) .", "/ wake systems is difficult due to the many checks and balances that ensure homeostasis ." ], [ "the co - morbidity of sleep disorders with neurodegenerative diseases suggests that changes in many of these neural areas manifests in sleep / wake and circadian dysfunction .", "it is crucial that we immediately invest our energies and resources in understanding these mechanisms as well as in the dissemination and implementation of current knowledge and therapies to the public .", "additionally there may be differential plasticity and compensation in the integration of these neural systems , making the identification of applicable therapies very difficult .", "a few points worth considering are as follows : sleep is a basic need that is made secondary to work schedules and some leisure activities for many adults . in developing", "it is likely that several brain regions are affected and that there are individual differences in how the sleep / wake and circadian networks degrade .", "the fragmented sleep / wake pattern seen in aging individuals can be due to the degeneration or dysfunction of the circadian and sleep / wake networks ." ], [ "the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest ." ] ]

[ [ "it is well known that whole breast irradiation ( wbi ) after breast conserving surgeries for patients with early infiltrating breast carcinoma ( bc ) significantly reduces the likelihood of local recurrence ( lr ) .", "the possibility of delivering intraoperative radiotherapy ( iort ) with electrons , without dedicated equipment , is very attractive . addressing this issue , the purpose of our paper was to assess the efficacy , toxicity , and cosmetic outcomes of iort delivered by standard linacs , during breast conserving surgeries for the treatment of early breast cancer .", "there are several evidences that lr is a predisposing factor for systemic metastasis [ 24 ] and , within this scope , radiotherapy ( rt ) is very useful for treating residual tumor cells after the surgery .", "there is no consensus , however , regarding whether the entire breast needs to be irradiated .", "the accelerated partial breast irradiation ( apbi ) concept , based on confining the irradiation to the vicinity of the tumour bed , shortening the course of the treatment and allowing more convenience for patients , has contributed to changes in the rt paradigms [ 6 , 7 ] .", "the most used schedule for wbi is 50 gy delivered in 5 weeks using conventional fractionation ." ], [ "briefly , the treated breast is compared with the contralateral one and the result is classified as excellent ( minimal or no difference in the size or shape ) ; good ( mild asymmetry in the size or shape ) ; fair ( obvious differences in the size and/or shape ) ; and poor ( marked change in the appearance involving more than 1/4 of the breast ) .", "as of july 2012 , 187 women with diagnosis of bc by percutaneous biopsy were enrolled .", "the presence of seromas , hematomas , fat necrosis , wound infections , and dehiscences was investigated at all time points after surgery .", "lr was considered as a true relapse ( tr ) , which represents regrowth of residual malignant cells in the same region of the primary tumour , or a second primary tumour ( spt ) , representing tumor growth in another quadrant , suggesting a distinct clonal origin .", "patients were eligible if they had unicentric invasive ductal carcinoma , with less than 3.0 cm at the largest diameter confirmed by mammography , ultrasonography , and magnetic resonance imaging ( mri ) .", "patients were considered ineligible if any of the following features were present : skin involvement , history of bc in the contralateral breast , or intraoperative microscopic findings of involvement of surgical margins or sentinel node ( sn ) .", "the breast conserving surgeries were performed at an operating theater located inside the radiotherapy department , contiguous to the linac suite ." ], [ "the esthetic outcomes have shown 70.3% excellent , 14.4% good , 3.9% regular , and 3.2% of bad results . from the entire cohort ,", "of the 187 enrolled patients , 35 ( 18.7% ) were intraoperatively excluded because of sn positivity ( 18 patients ) , difficulty in obtaining clear margins ( 11 patients ) , multicentricity / multifocality ( 3 patients ) , muscle infiltration ( 1 patient ) , t3.0 cm ( 1 patient ) , and no sn identification ( 1 patient ) .", "the cumulative incidence of lr as the first unfavorable event was 3.2% ( 95% ci : 0.88.1 ) ( figure 3 ) . among the 5 cases of lr in the entire cohort 4 were considered to be a tr , and one had a failure in a quadrant other than the index lesion at 30-month follow - up , consistent with spt . regarding other failures , two patients ( 1.3% ) developed distant metastases , three had axillary failure ( 1.9% ) , and one patient had a contralateral tumor ( 0.6% ) .", "there were also 3 cases of breast lymph edema and 2 cases of nipple retraction .", "evidence of late toxicity , observed after at least 6 months of follow - up , was seen in 45 patients ( 29.6% ) in a median time of 8 months ( range 824 ) ." ], [ "we have previously reported our outcomes with focus on technical aspects , and the highlights of the use of nondedicated machine were to explore its capability of producing higher electron beam energies rather than dedicated machines and to check the possibility of misalignment between the collimator and the shielding disks by obtaining portal films using photon beams .", "the technique was demonstrated to be feasible and was successfully implemented , with a very short learning curve .", "iort with electrons delivered by conventional linacs , immediately after a wide local excision , presented the expected results until now , with very good local control and cosmetic outcomes and a low toxicity rate .", "different rt techniques can be used with this purpose and , given that intraoperative rt with standard linacs has previously been used to treat abdominal tumors , we decided to use this form of treatment during breast conserving surgeries .", "breast conserving surgery followed by external wbi is a well established treatment for most women with early infiltrating bc [ 24 , 25 ] .", "selected patients with early infiltrating breast carcinomas may benefit from the technique , which may represent an interesting option for developing countries ." ] ]

[ [ "cell regeneration therapy is a promising new approach for myocardial repair , [ 1 , 2 ] and in this context , there has been considerable basic research on the mechanisms of cell development into cardiomyocytes using somatic and embryonic stem ( es ) cells as well as embryonic carcinoma cells [ 36 ] . ", "p19 embryonic carcinoma cells are one of the first among such cells to demonstrate differentiation into cardiomyocytes and have contributed extensively to the elucidation of the development mechanisms from stem cells into cardiomyocytes [ 4 , 5 , 8 ] . ", ", we also introduce a software program , visorhythm , which can analyze the temporal variations in the beating rhythms on moving images and chart correlograms displaying the oscillated rhythms on a windows computer . because the spontaneously beating cardiomyocytes differentiated from p19cl6-a1 cells form large cell clusters , their contractions are large and strong . ", ", we attempted to establish a subline from p19cl6 cells , and accordingly , we could introduce a new subline of cells , that is , p19cl6-a1 cells , that could efficiently and stably differentiate into cardiomyocytes by a differentiation method based on the double stimulation method with many modifications . in the present study", "it is one of the leading causes of death in advanced countries because adult cardiomyocytes are highly differentiated and have a limited regenerative capacity ; therefore , significant loss of myocardium is mostly irreversible . " ], [ "the differentiation efficiencies of the subline , p19cl6-a1 , and the parent cell line , p19cl6 , were compared . ", "we examined the pharmacological reactions of spontaneously beating cardiomyocytes differentiated from the p19cl6-a1 cells to evaluate whether they are useful cellular tools for pharmacological screening tests . ", "both cell types were collected for the cardiac differentiation experiment ; however , the latter were considerably more efficient in differentiating into cardiomyocytes . among the several differentiation methods , the one proposed by ohtsu et al", "accordingly , we found a subclone , designated a1 , which is the most efficiently differentiated into cardiomyocytes under the differentiation conditions below and used it for further experiments to evaluate the differentiation efficiency . ", ". elicited most efficient cardiomyocyte differentiation from parent p19cl6 cells as long as the experiment was in vitro in our laboratory ; however , it also led to a fundamental difficulty , that is , high variations in the differentiation efficiencies among individual experiments . ", "hence , we modified the above method in order to adapt it to our subclonal cells as well as to the parent cells . " ], [ "we examined the pharmacological reactions of the spontaneously beating cells differentiated from p19cl6-a1 cells by the developed protocol . for this purpose , we employed ibmx and ouabain as cardiotonic reagents , and both of them increased the beating rates . ", "we also examined -mhc expression in the ventricles of 8-week - old adult mice and 16.5 dpc fetuses by rt - pcr to compare -mhc expression in the tissues with that in the p19cl6-a1 cells differentiated by the developed protocol on day 16 . ", "these data indicate that the p19cl6-a1 cells and visorhythm are useful tools for pharmacological screening tests .", ", we examined the expression of the cardiac - specific transcription factors , gata4 and nkx2 - 5 , and of the cardiac - specific myosin heavy chain , -mhc , by rt - pcr on the respective cells with the respective differentiation protocols listed in table 1 on days 0 , 3 , 7 , and 16 . ", "the moving images of the beating cells were recorded before and after addition of serial dilutions of each reagent . to determine the temporal variations in the beating rhythms in detail , we developed the software , visorhythm , to analyze them based on moving images and chart correlograms displaying the oscillated rhythms . " ], [ "we introduced a new software , visorhythm , that can analyze the temporal variations in the beating rhythms and can chart correlograms displaying the oscillated rhythms up to 6 areas on a single moving image simultaneously . using p19cl6-a1-derived cardiomyocytes and the software", "these indicate that a combination of p19cl6-a1 cells and visorhythm is a useful tool that can provide invaluable assistance in inotropic drug discovery , drug screening , and toxicity testing .", ", we introduced p19cl6-a1 , a clonal derivative of p19cl6 cells , which differentiated into cardiomyocytes most efficiently among the 3 cell lines subjected to double stimulation with 5-aza and dmso in adhesion culture as reported by ohtsu et al .", "therefore it can also analyze synchronization between cardiomyocytes . in conclusion , we used double stimulation with 5-aza and dmso in this study and showed that p19cl6-a1 cells , a new clonal derivative of p19cl6 cells , differentiated into cardiomyocytes more efficiently than the parent cells . ", "here we have introduced visorhythm to analyze temporal variations in beating rhythms of cardiomyocytes based on moving images and chart correlograms displaying the oscillated rhythms . ", ", we demonstrated that the correlograms could clearly display the enhancement of beating rates by cardiotonic reagents . " ] ]

[ [ "single incision laparoscopic surgery ( sils ) for cholecystectomy procedure has been introduced as early as 1999 to achieve less pain , less scarring , and less hospitalization period .", "one of the major difficulties of this procedure seems to be the traction of the gallbladder in order to expose the tissues during operation without additional ports .", "the use of transabdominal 20 nylon sutures attached to keith needles and the use of a kirschner wire hook introduced through subcostal area are reported methods used for traction of gallbladder and better exposition of the calot triangle .", "herein , we describe our technique in establishing single port access for cholecystectomy in five patients that involves the use of a 2 mm in diameter grasper , karl storz 27290f , that is generally used by urologists for percutaneous nephrolithiasis intervention .", "however , all these techniques consist puncture of the gallbladder with sharp needles especially if it is distended and carry the risk of bile leakage and contamination afterwards ." ], [ "no complications including gas leakage around the minigrasper were encountered during and after the surgery .", "this atraumatic device helped to mobilize gallbladder whenever needed during surgery without causing any wound or leakage .", "then , the dissection of the gallbladder was completed in a standard fashion from bottom to top and after the organ was dissected free from the liver , it was removed directly through the umbilical incision . ", "followup was done in the first month and minimal scarring was observed in the umbilicus and the minigraspers ' small incision was almost invisible .", "it is used to hold the fundus of the gallbladder gently and push the organ in an cephalad direction to visualize calot 's triangle ( figure 3 ) ." ], [ "there are many technical challenges in silc surgery as one of them seems to be the retraction of the fundus cephalad and traction of the hartmann 's pouch laterally to ensure safe cholecystectomy . for this purpose ,", "single incision laparoscopic cholecystectomy ( silc ) was first described by navarra et al . in 1997 ,", ", silc technique has been performed by many clinicians with promising results and many advantages like few complications , acceptable operation period , less scarring , less pain , and quicker recovery .", "we believe learning curve would be low and it would be possible to significantly decline operation periods in following patients . in conclusion , with the help of this instrument the operation period may be lessened , less scarring is achieved and surgical procedure is done more easily and safely without any additional costs .", "use of this instrument has led no perforation and leakage of bile in the patients . through a very small incision , 2 mm in length , without using any port ," ] ]

[ [ ", we describe a young girl with bilateral wilms tumor who had marked tumor response after 12 weeks of chemotherapy .", "her case illustrates that tumor lysis precautions should be considered in children with a large amount of disease who undergo neoadjuvant treatment and that pathologic interpretation of the tumor is possible even after many cycles of chemotherapy .", "frequently one kidney will have a much larger tumor burden , as in the present case , and surgery would consist of complete nephrectomy for one side and partial nephrectomy for the other .", "however , as many as 15% of stage v wilms tumor patients treated in this manner eventually develop chronic renal failure by age 20 compared with 1% of unilateral wilms tumor patients , prompting efforts to surgically spare as much normal renal tissue as possible .", "children 's oncology group trial aren0534calls for pre - operative neoadjuvant chemotherapy to be given in order to shrink tumors to facilitate partial nephrectomies to maximize preservation of normal renal tissue . here", "wilms tumor is the most common renal tumor in children , peaking at 23 years of age .", "surgery is then followed by several weeks of adjuvant chemotherapy , with radiotherapy used mainly for cases of tumor rupture or peritoneal seeding . though primary kidney resection has long been the cornerstone of effective treatment for wilms tumors , this approach has recently been reevaluated in the context of synchronous bilateral disease ." ], [ "note that the architecture of the tumor is still well preserved , confirming a diagnosis of wilms tumor .", "note that the architecture of the tumor is still well preserved , confirming a diagnosis of wilms tumor .", "( a ) lower - power power image ( 100 ) showing the area of anaplasia ( black triangle ) immediately adjacent to an area of scarring and fibrosis ( white triangle ) , ( b ) a region of non - anaplastic glandular wilms tumor ( 400 ) , ( c ) anaplastic focus of disease ( white triangle ; 400 ) .", "the patient was given a presumptive diagnosis of bilateral ( stage v ) wilms tumor .", "( a ) lower - power power image ( 100 ) showing the area of anaplasia ( black triangle ) immediately adjacent to an area of scarring and fibrosis ( white triangle ) , ( b ) a region of non - anaplastic glandular wilms tumor ( 400 ) , ( c ) anaplastic focus of disease ( white triangle ; 400 ) .", "we decided to administer another 6 weeks of chemotherapy to improve her candidacy for right partial nephrectomy instead of whole nephrectomy . however , despite further tumor shrinkage , total nephrectomy eventually had to be performed for the right kidney because no clear surgical plane could be identified at the time of resection ( fig . " ], [ "our case illustrates that wilms tumor , being a chemosensitive embryonal malignancy of childhood , can also be associated with tumor lysis syndrome . in the past", "this case illustrates that if surgery is postponed , tumor lysis precautions should be considered when chemotherapy is given to patients with large wilms tumors .", "however , current high - risk wilms tumor protocols , as apply to patients with bilateral disease , are designed to reduce long - term risk of renal failure by shrinking tumors with chemotherapy to enable nephron - sparing sub - total nephrectomy .", "clinical trials by siop ( international society of paediatric oncology ) and other consortia have found that pre - nephrectomy chemotherapy may decrease the stage of disease and risk of tumor rupture during local control ; however , this approach brings risks of tumor lysis syndrome , veno - occlusive disease and potential interference with tumor staging and pathologic diagnosis . in the present case ,", "laboratory findings of tumor lysis syndrome include hyperuricemia , hyperkalemia and hyperphosphatemia with secondary hypocalcemia ." ] ]

[ [ "the goal of the current study is to determine whether genotypes predicted subjective physiological and affective responses to a 30-minute bout of aerobic exercise among sedentary individuals .", "briefly , we proposed that genetic factors influence how an individual physiologically ( e.g. , body - temperature regulation ) and subjectively ( e.g. , affective response , perceived exertion ) responds to the experience of exercise .", "thus , each of these snps was investigated in the current study in order to determine potential relationships with phenotypes related to physiological and affective response to an acute bout of aerobic exercise .", "based on the literature and on our prior analysis of the relationships among a range of exercise response phenotypes ( see for analysis and detailed information on the rationale for selection of phenotypes ) , the variables from the physiological responses to exercise domain included in our analysis were temperature , heart rate , systolic blood pressure , lactate , and norepinephrine , all measured as change scores from immediately prior to a bout of exercise to 30-minutes into the bout ( just before the end of the bout ) .", "the variables selected from the subjective experience of exercise domain were affect ( i.e. , positive affect and affective valence ) , perceived pain , and rate of perceived exertion ( rpe ) , which were also change scores measured from prior to the bout to just before the end of the bout .", "there is also research to suggest that immune function changes may mediate the relationship between physical activity and cancer development ." ], [ "participants included in the present analysis were a subset of 238 individuals from a larger intervention study ( costride ) [ 17 , 40 ] in which participants were randomly assigned to the stride exercise intervention ( costride ) or a health - and - wellness contact control condition ( hw ) .", "prior to randomization to intervention condition and after giving informed consent , participants completed three sessions : ( 1 ) an orientation ( baseline ) session in which self - report questionnaire assessments were completed , ( 2 ) a vo2 max cardiovascular fitness assessment , and ( 3 ) a submaximal exercise session . prior to exercise sessions , each participant was instructed to eat a meal comprised of both carbohydrates and protein and to consume at least 300 calories two hours before coming into the lab ( e.g. , if a participant is scheduled to come into the lab at 12:00 p.m. a researcher instructed him / her to eat the 300 calorie meal at 10:00 a.m. and no later ) .", "as described in detail below , we used the illumina human 1 m duov3 dna analysis beadchip to genotype the dna samples .", "although we used a genome - wide approach to genotyping , we only tested a total of 14 snps which were selected for analysis in this study based upon their potential association with aerobic exercise response phenotypes suggested by prior studies ( see table 2 for hardy - weinberg p values and minor allele frequencies for each snp tested ) .", "our search was conducted primarily using pubmed , and was focused on snps that were directly associated with specific phenotypes of interest and to traits that may be associated with those phenotypes .", "thus , individuals with the most complete baseline data ( baseline dna sample , self - report questionnaire assessments , vo2 max fitness assessment , and submaximal exercise session ) were selected to be genotyped out of the full sample ." ], [ "as can be seen in figure 1 , individuals with the tt genotype of rs2360969 showed the highest temperature after 30 minutes of aerobic exercise , controlling for baseline temperature . in figure 2 , we show that individuals with the ag / gg genotypes on rs1799971 show greater rpe after 30 minutes of aerobic exercise than individuals with the aa genotype , controlling for baseline rpe . in figure 3 , we show that individuals with the cc genotype in rs8044769 show the highest ratings of positive affect after 30 minutes of aerobic exercise , controlling for baseline positive affect .", "these same snps were also significantly associated with vo2 max ( rs2253206 , r = .17 , p = .01 ; rs2360969 , r = .14 p = .049 ) , such that for rs2253206 , individuals with the g allele had higher vo2 max , and for rs2360969 , individuals with the c allele had higher vo2 max . the oprm1 snp rs1799971 was significantly associated with lactate change during exercise ( r = .17 , p = .02 ) , norepinephrine change during exercise ( r = .16 , p = .03 ) , and change in rpe during exercise ( r = .14 , p = .048 ) , indicating that individuals with the rare g allele had greater changes in lactate , norepinephrine , and rate of perceived exertion change over the course of exercise .", "the fto snp rs9941349 was significantly related to change in systolic blood pressure during exercise ( r = .15 , p = .04 ) , and individuals with the t allele experienced greater increases in systolic blood pressure during exercise .", "the fto snp rs7201850 was significantly related to change in systolic blood pressure during exercise ( r = .17 , p = .027 ) , with individuals possessing the t allele experiencing greater increases in systolic blood pressure over the course of the exercise bout ." ], [ "the present study replicated prior findings suggesting that snps in the creb1 , fto , oprm1 , slit2 , and fam5c genes are all related to phenotypes encompassing various responses to exercise .", "so , although the correlations between genotype and exercise response found in this study are not large , they represent a necessary first step in forming genetic composite scores that are likely to be more highly correlated and significantly predictive of exercise responses . in summary , linking snps to specific physiological and psychological mechanisms that contribute to exercise response will assist in informing individually tailored exercise programs , as well as deepen our understanding of the relationship between genetics , physiology , and psychology underlying health behaviors associated with cancer prevention .", "overall , replication is needed in order to confirm findings from the present study , and to better understand the functional significance of these genes and snps in relation to physiological and subjective responses to aerobic exercise .", "our study tested conceptually relevant phenotypes that to date had not been explored in this way inanyother exercise research . given that the physiological response to aerobic exercise involves a complex interplay of metabolic , cardiovascular , musculoskeletal , ventilator , and hormonal functions , these genes and snps are likely to explain only a small portion of the variability in individual differences in response to aerobic exercise .", "the results of our study suggest that it is also associated with change in norepinephrine in response to exercise . to date , research has not examined the relationship between fam5c and aerobic exercise response .", "further research is needed to elucidate more specific relationships between slit2 and response to aerobic exercise ." ], [ "future studies designed to test genetic influences on a wide range of exercise response phenotypes would help to advance this goal , potentially leading to a panel of markers important for characterizing the physiological and subjective response to exercise .", "moreover , giving feedback to sedentary individuals regarding the genetic basis for their strengths and weaknesses in fitness / exercise / sports activities could be a potentially useful motivational tool for increasing exercise behavior [ 13 , 66 ] . in sum , expanding our understanding of the association between genetics and exercise response phenotypes has a myriad of implications for helping to increase exercise behavior in sedentary individuals , an outcome which is crucially important for the reduction of morbidity and mortality associated with cancer .", "the purpose of this paper was to explore the genetic underpinnings of individual physiological and subjective responses to aerobic exercise .", "the relationship between particular genetic variants and responses to exercise has important implications for the prevention of cancer via increasing exercise behavior in sedentary populations .", "one strength of this study was its focus on a sedentary population , a group that has been rarely tested in terms of associations between genetics and exercise phenotypes ." ] ]

[ [ "the purpose of this retrospective study was therefore to investigate any possible correlation between low blood levels of vitamin d and early implant failure ( failure occurring in the four months prior to the full restoration of the implant , because of a lack of osseointegration or because of infection ) .", "dental implants are now a reliable solution for the functional and esthetic rehabilitation of partially and completely edentulous patients ; this has been demonstrated by long - term clinical trials , with survival rates of greater than 95% [ 13 ] . in order to achieve long - term survival , osseointegration of the dental implant", "osseointegration is a complex phenomenon and depends on many factors ; some are related to the implant ( material , macroscopic design , and implant surface ) , others to the surgical - prosthetic protocol ( surgical technique , loading conditions , and time ) , and others to the patient ( quantity / quality of bone at the receiving site and the host response ) [ 4 , 5 ] . although survival rates of dental implants are now high , there still remains a seemingly unavoidable number of failures : either cases in which correctly placed implants do not integrate with the bone or cases of peri - implant tissue infection [ 6 , 7 ] . to be specific , failure to osseointegrate and peri - implantitis are the most frequent causes of early implant failure [ 3 , 6 , 7 ] ." ], [ "all patients who had been treated with morse - taper connection dental implants ( leone implant system , florence , italy ) [ 3 , 8 ] inserted to support fixed prosthetic restorations in one single dental centre ( gravedona , como , italy ) , in the period between january 2003 and december 2015 , were evaluated for possible enrollment into this retrospective study .", "early implant failure , occurring within 4 months after implant placement and therefore prior to placement of the prosthetic restoration and the functional load of the implant , was the primary outcome studied .", "patients were enrolled into the study if they were over 18 years of age , had good oral and general health , and had not undergone bone regenerative therapy prior to implant placement .", "the influence of different variables on implant survival was taken into consideration : gender ( male or female ) , age at time of surgery ( three age groups were examined : < 40 , 4060 years , and > 60 years ) , smoking habits ( regardless of the actual number of cigarettes smoked ) , a history of chronic periodontitis , and serum levels of vitamin d. in the analysis of serum levels of vitamin d , three classes of patients were considered : severely deficient patients ( serum vitamin d < 10 ng / ml ) , patients with low levels ( serum vitamin d between 10 and 30 ng / ml ) , and patients with adequate levels ( serum vitamin d > 30 ng / ml ) .", "the event was implant failure : thus in patients receiving more than one implant , the occurrence of even a single implant failure led to the patient being classified as a failure . " ], [ "the distribution of patients by groups , with relative incidence of failures , was reported in table 1 . in total , 27 early failures were recorded ( 19 due to failure of osseointegration and 8 due to peri - implant tissue infection ) , with an overall incidence of 3.2% .", "of the 915 patients originally evaluated for enrollment in this study , 93 presented with conditions corresponding to the exclusion criteria and were therefore excluded from the assessment . by contrast , 822 patients ( mean age 57.3 14.2 years ; median age 58 ; range 1890 ; and 95% ci , 56.358.2 ) , receiving 1625 implants , did not have any of the conditions contained in the exclusion criteria and were therefore enrolled into this retrospective study .", "no differences were observed in the incidence of early failures between males and females ( p = 0.97 ) nor according to age at time of surgery ( p = 0.98 ) .", "although the percentage of early failures in smokers was slightly higher than that detected in nonsmokers , there was no statistically significant difference ( p = 0.56 ) between these two groups of patients . the same was true for patients with a history of periodontal disease ; they displayed a slightly higher incidence of early failures than patients who had not been affected by periodontitis , but this difference was not significant ( p = 0.73 ) .", "the average serum level of vitamin d in the general population was 29.9 ng / ml ( 12.1 ; median 29 ; range 573 ; and 95% ci , 29.130.7 ) . in patients in whom early implant failure occurred ,", "similar results ( p = 0.14 ) were obtained comparing the incidence of failures in the group of severely deficient patients ( 2/22 : 9.0% ) with the incidence of failures in all other patients ( 25/800 : 3.1% ) . finally , the statistical analysis did not reveal a significant difference ( p = 0.13 ) when comparing the incidence of failures in the group of patients with serum vitamin d levels > 30 ng / ml ( 9/394 : 2.2% ) with the incidence of failures in all other patients ( 18/428 : 4.2% ) ." ], [ "a relatively small number of experimental studies has attempted to investigate the effects of vitamin d on the osseointegration of dental implants [ 2432 ] .", "the majority of these studies would appear to indicate a positive effect of vitamin d on osseointegration , but it is not yet entirely clear whether supplementation would promote the healing of peri - implant bone tissue clinically [ 24 , 3335 ] .", "finally , liu et al . reported that the administration of vitamin d could increase the fixation of dental implants in mice suffering from chronic kidney disease . a further possibility for study , in order to understand the effects of the administration of vitamin d on bone healing of the peri - implant tissues , is that of coating the implant surface with vitamin d [ 3032 ] .", "in the light of this , the administration of vitamin d in the weeks prior to placement of a dental implant could be useful , particularly in patients with severe deficiency states ; in these patients , vitamin d supplementation should be maintained for the whole life , in order to guarantee a good remodelling of the bone around the implant .", "unfortunately , very few clinical studies have so far investigated the effects of vitamin d deficiency on osseointegration and on bone regeneration in dentistry [ 3335 ] .", "therefore , randomized , controlled clinical trials are needed to confirm the presence of an association between low serum levels of vitamin d and an increase in the incidence of early failure in implantology ." ], [ "our retrospective clinical study aimed to investigate if there is a link between low levels of vitamin d in the blood and an increased risk of early implant failures . although the incidence of early implant failures was higher in patients with low serum levels of vitamin d , our study failed in proving an effective link between low levels of vitamin d in the blood and an increased risk of early implant failure .", "until now , very few studies , and those mainly on animal models , have involved assessing the influence of blood levels of vitamin d levels on the osseointegration of dental implants .", "further higher level studies ( prospective controlled trials or , even better , randomized controlled clinical trials ) with a more rigorous statistical analysis are therefore needed to investigate this issue .", "if an association between low serum levels of vitamin d and higher risk of early implant failure could be demonstrated , the clinician could give a set dose of vitamin d in the weeks before surgery , in order to normalize serum levels and obtain a positive effect on the healing process .", "although most of these studies have shown that the administration of vitamin d can improve the healing of the peri - implant bone tissue , it is not yet clear whether vitamin d supplements can promote the osseointegration of dental implants ." ] ]

[ [ "this study was done to compare the clinical and radiological outcome of mta or epoxy resin as a root canal sealers compared to zinc oxide eugenol sealer using gutta - percha as the obturating material in teeth with periapical radiolucency .", "evaluation of post - operative pain with visual analogue scale ( vas ) , periapical healing with periapical index ( pai ) are widely used methods and morphometric evaluation with vixwin pro digital image analysis software is a new , reliable and accurate technique .", "zinc oxide eugenol is an efficient and proven root canal sealer while epoxy resin has equivalent properties to compete with it .", "introduced mineral trioxide aggregate ( mta ) , a tricalcium silicate cement as a perforation repair material ." ], [ "the cases were assigned into any one of the following groups : \n group 1 : zinc oxide eugenol ( tubliseal ) as root canal sealer ( n = 15)group 2 : epoxy resin ( ah plus ) as root canal sealer ( n = 15)group 3 : mta ( proroot mta ) as root canal sealer ( n = 15 ) . \n ", "group 1 : zinc oxide eugenol ( tubliseal ) as root canal sealer ( n = 15 ) group 2 : epoxy resin ( ah plus ) as root canal sealer ( n = 15 ) group 3 : mta ( proroot mta ) as root canal sealer ( n = 15 ) .", "caries was excavated and if necessary pre - endodontic management was done with composite resin .", "this study was conducted in patients in an age group of 18 - 50 years with teeth indicated for root canal treatment .", "the 45 teeth indicated for root canal treatment were allotted into three groups with 15 teeth in each group .", "teeth with calcified canals , retreatment cases , pregnant patients , systemic diseases and lactating mothers were excluded ." ], [ "before commencing the evaluation for pain , every patient was explained about the usage of vas using the following criteria : immediately after obturation and placement of coronal seal every patient was asked to mark the pain intensity using a 10 cm vas .", "all subjects were recalled after 1 week of post - obturation for evaluation of pain and clinically examined ." ], [ "immediate post - obturation radiograph ( base line data ) was evaluated for pai score and recorded in the evaluation sheet using the criteria described by orstavik . at the 6 month follow - up visit ,", "again a radiograph was taken using parallel cone technique and the pai score was assessed [ figure 1 ] .", "sample radiographs : ( a ) pre - operative , ( b ) immediate post - operative and ( c ) after 6 months for the groups respectively" ], [ "the area measured was recorded in the evaluation sheet . at the 6 month , again the same procedure was repeated and the area was measured using the same criteria as mentioned before [ figure 2 ] .", "the image was then subjected to morphometric area measurement with the area measurement tool in the vixwin pro digital image analysis software ( version 1.3 , gendex dental systems , hatfiled , pa , usa ) by outlining the radiolucency .", "immediately after obturation , a digital radiograph was taken ( base line data ) with gendex rvg unit for morphometric analysis ( gendex dental systems , hatfiled , pa , usa ) ." ], [ "wilcoxon 's signed rank test was used for comparison of pain and pai score within the groups at different intervals .", "wilcoxon 's signed rank test was used for the comparison of area among the three groups at base line and at 6 months .", "kruskall - wallis analysis of variance test followed by mann - whitney u test was used for comparison of pain and pai scores between groups at different intervals ." ], [ "pain comparison was performed intergroup and intragroup at three specific time periods . the standard deviation ( sd ) of vas score immediately after obturation for the groups are 8.46 ( 11.26 ) , 10.46 ( 14.86 ) and 7.63 ( 8.46 ) respectively .", "comparison of pain between groups measured by vas at baseline , 1 week and at 6 months comparison of pain within group measured by vas at baseline , 1 week and at 6 months there was a highly significant ( hs ) difference in the pai score was found on comparing the base line and at 6 months", "there was a hs difference in the area measurement comparing the base line and at 6 months , but no difference among the groups at any interval [ table 4 ] .", "group 2 was found to have more vas score ( p = 0.19 ) than other two groups but was statistically not significant ( p = 0.19 ) .", "comparison of periapical index score within groups at baseline and at 6 months the sd of area measured immediately after obturation for the groups were 8.14 ( 8.40 ) , 9.57 ( 9.20 ) and 4.32 ( 5.20 ) respectively and area after 6 months were 5.4 ( 5.7 ) , 6.80 ( 8.11 ) and 4.14 ( 3.93 ) respectively .", "when the pain was compared within the group at 1 week and at 6 months , there was no difference ." ], [ "pain comparison was performed intergroup and intragroup at three specific time periods . the standard deviation ( sd ) of vas score immediately after obturation for the groups are 8.46 ( 11.26 ) , 10.46 ( 14.86 ) and 7.63 ( 8.46 ) respectively .", "group 2 was found to have more vas score ( p = 0.19 ) than other two groups but was statistically not significant ( p = 0.19 ) .", "comparison of pain between groups measured by vas at baseline , 1 week and at 6 months comparison of pain within group measured by vas at baseline , 1 week and at 6 months", "when the pain was compared within the group at 1 week and at 6 months , there was no difference .", "vas score after 6 months were 1.63 , 1.06 and 0.33 respectively and there was no statistically significant difference [ tables 1 and 2 ] ." ], [ "there was a highly significant ( hs ) difference in the pai score was found on comparing the base line and at 6 months .", "however , no difference among the groups was found at any interval [ table 3 ] ." ], [ "the sd of area measured immediately after obturation for the groups were 8.14 ( 8.40 ) , 9.57 ( 9.20 ) and 4.32 ( 5.20 ) respectively and area after 6 months were 5.4 ( 5.7 ) , 6.80 ( 8.11 ) and 4.14 ( 3.93 ) respectively .", "there was a hs difference in the area measurement comparing the base line and at 6 months , but no difference among the groups at any interval [ table 4 ] ." ], [ "baseline values of vas score , pai scores and area measurement zinc oxide eugenol was used as a positive control in this study .", "root canal sealers along with obturation material will provide a bacteria proof seal of the root canal system , preventing the leeway space and communications between the intracanal and extracanal environments .", "no difference in the age , sex , tooth type , tooth distribution , root morphology , pai score and area measurement at baseline suggest that the groups were equally distributed [ table 5 ] .", "the present study was designed to compare the clinical and radiological outcome of three different root canal sealers .", "the scope of this study was to evaluate the effectiveness of mta as a root canal sealer considering its radiological and clinical success rate , usage and feasibility ." ], [ "among the three root canal sealers used in this study , no sealer was proven to be superior .", "further long - term clinical trials with more criteria should be conducted to conclude the superiority among these materials .", "mta has performed equally well when compared with the zinc oxide eugenol and ah plus ." ] ]

[ [ "in addition , the regulation of ngf expression by inflammatory cytokines in synovial macrophages and fibroblasts was also examined .", ", we characterized the expression profiles of several inflammatory cytokines and ngf in the st of str / ort mice .", "in addition , because only a few effective disease - modifying drugs are available for oa [ 5 , 6 ] , a better understanding of the mechanisms that drive oa pain is required to guide drug development . nerve growth factor ( ngf ) is a widely known pain mediator and plays a critical role in the modulation of oa pain [ 811 ] .", "osteoarthritis ( oa ) is characterized by cartilage breakdown , synovial fibrosis , and osteophyte formation .", "in addition , we reported that compared to synovial fibroblasts ( cd11b ) , synovial macrophages produce high levels of il-1 and tnf- in str / ort mice . here", "evidence from these studies suggests that the activity of ngf is mediated by inflammatory cytokines ." ], [ "the gene expression levels in the st of str / ort mice were compared with those in the st of c57bl/6j mice ( str / ort / c57bl6j ) .", "in addition , the gene expression levels in cd11b+ cells were compared with those in cd11b cells ( cd11b+/cd11b ) .", "the numbers of cgrp- and trpv - positive cells were counted , and the proportion of these cells to the total number of nucleated cells in drg was calculated for each drg sample .", "tnf- , il-1 , il-6 , and ngf expression in the cells was analyzed by reverse transcription - polymerase chain reaction ( rt pcr ) .", ", synovial fibroblasts were incubated with either mouse recombinant tnf- ( 25 ng / ml ) , il-1 ( 50 ng / ml ) , or il-6 ( 100 ng / ml ) ( biolegend , san diego , ca , usa ) for 24 h. cells that were not treated with any cytokines were used as controls . to examine the effect of tnf- on synovial macrophages and fibroblasts ,", "the treated and control cells were harvested for total rna isolation , as described above , and ngf expression was analyzed by rt pcr ." ], [ "real - time pcr analysis of the genes encoding tnf- , il-1 , il-6 , and ngf showed that the expression levels of these genes were significantly elevated in the st of str / ort mice compared to those in control c57bl/6j mice ( figures 1(a)1(d ) ) . activated", "real - time pcr analysis revealed that the gene expression of ngf increased significantly in isolated synovial cells in the presence of exogenously added tnf- and il-1 compared to untreated control cells ( figure 3 ) .", "ngf expression was also significantly increased in the presence of exogenously added il-1 in isolated populations of synovial fibroblasts , but not in synovial macrophages ( figure 4(b ) ) . to investigate pain - related sensory innervation by ngf , the proportion of trpv1- and cgrp - positive cells in the drg of str / ort mice was investigated by immunohistochemistry .", "in contrast , the gene expression of ngf was not affected in il-6-treated synovial cells ( figure 3 ) ." ], [ "in the present study investigating the mechanisms underlying the regulation of ngf and development of oa pain , higher expression of the genes encoding tnf- , il-1 , il-6 , and ngf was observed in the st of an oa str / ort mouse model compared to that in c57bl/6j mice .", "tnf- and il-1 may therefore regulate ngf signaling in oa joints and be suitable therapeutic targets for treating oa pain .", "finally , present study did not confirm that the protein levels of these cytokines correlated with the expression levels . in conclusion , the present results support the hypothesis that tnf- regulates ngf expression in synovial fibroblasts and macrophages and il-1 regulates ngf expression in synovial fibroblasts in oa mice .", "notably , the treatment of cultured synovial cells with tnf- and il-1 stimulated ngf expression and tnf- also stimulated ngf expression in cd11b - positive and cd11b - negative cell fractions ." ] ]

[ [ "some studies have reported an association between obi and elevated transaminase ; therefore identification of obi is of importance .", "notably , there is considerable variation in prevalence of hiv / hbv coinfection according to geographic regions and exposure risk .", "this is particularly important as exposure to hbv is common among hiv - infected cases because of shared routes of transmission .", "\n hepatitis b virus ( hbv ) is a major health problem , with approximately 400 million chronically infected people worldwide , and 1560% of the normal population in many african countries may be positive for one or more of the serological markers of hepatitis b virus infection .", "hiv coinfection has been reported to modify the natural history of hbv with potential consequences on morbidity and mortality .", "successful implementation of art leads to immune reconstitution that can potentially result in immune mediated liver injury in the setting of hbv coinfection ." ], [ "of the 1,200 hiv - infected patients enrolled in the haart clinic of the specialist hospital , ikole , ekiti state , nigeria , from october , 2012 , to april , 2013 , we identified 980 hbsag negative patients ( art - nave subjects ) . among them , 188 were selected for the study by a simple random method .", "all anti - hbc positive samples were retested for hbsag as well as for anti - hbc , and only repeat positive samples were included in the study .", "the presence of hbv dna was examined in all samples using a routine diagnostic pcr .", "all samples were tested for hbsag , anti - hbs , anti - hbc , anti - hcv , and anti - hiv using elisa ( drg diagnostics , marburg , germany ) .", "thermal cycling parameters remained the same as in the first pcr round except for the number of cycles that is increased to 40 cycles of amplification .", "primer pairs were designed from the highly conserved overlapping regions of the s and p genes of the hbv genome ." ], [ "hbv - plasmid dna was used to generate a standard curve following a serial 10-fold dilution .", "quantification of hbv dna was performed with quantitative real - time pcr using a previously described procedure in a geneamp 7300 sequence analyzer ( applied biosystems , perkin - elmer , foster city , ca ) ." ], [ "the chi - square test and fisher 's exact test were used to compare categorical data . for the purpose of our study ,", "mean age and all the numerical data were analysed using student 's t - test ." ], [ "serum levels of ast and alt were higher among patients with obi in comparison to anti - hbc positive hbv dna negative individuals , but the difference failed to reach standard significance ( p = 0.13 and p = 0.07 ) , respectively .", "the distribution of the study participants as per the 1993 revised classification system for hiv infection and expanded surveillance case definition for aids among adolescents and adults was as shown in table 4 . ", "thus , in the total study population , 21/188 ( 11.2% ) of patients were identified as obi and 62.5% of the obi patients had cd4 count less than 200 cells / mm .", "the comparison of different demographic , biochemical , and virological factors between hbv dna positive and negative cases was illustrated in table 3 .", "overall , 29/96 ( 29.2% ) of patients were reactive for anti - hbc , an indication of prior exposure to hbv dna , and majority 6/8 ( 75% ) of the patients were female ( table 2 ) .", "averagely the hbv viral load was < 50 copies / ml in the obi samples examined by quantitative pcr ." ], [ "the present study represents a comprehensive cross - sectional analysis of prevalence of obi in an art nave hiv positive cohort comprising various risk groups .", "this study describes the risk factors associated with obi , frequently of anti - hbc positivity and its possible values as a serological marker for identifying hiv - infected patients who benefit from hbv dna assay .", "we found the prevalence of occult hbv to be 11.2% among a random selected group of hiv - infected patients .", ". however , anti - hcv was not tested among the other hiv positive samples attending the specialist hospital , ikole , ekiti state , nigeria ." ], [ "overall , the present study highlights the need for screening hbv before the initiation of any haart containing anti - hbv regimens in hbv / hiv coinfected patients .", "a main implication of the presently viable data is therefore further emphasizing the need for efficient hbv vaccination programs .", "it necessitates the use of nat for effective laboratory diagnosis of occult hbv infections in hiv positive patients , especially in developing countries where these assays are not widely available ." ] ]

[ [ "this review will outline the evidence for the use of different treatment options for patients with intractable seizures . whilst the focus will be on the pharmacological options , we will also review the extent and quality of evidence supporting the efficacy of surgical , metabolic , neurostimulatory and herbal interventions in the context of the associated side - effects , safety and patient preferences .", "many of the new drugs have novel mechanisms of action and exhibit fewer drug - interactions . when considering the most appropriate choice of treatment", "this is of particular importance in children with refractory epilepsy , a large proportion of whom present specific age - dependent epilepsy syndromes .", "epilepsy is generally deemed intractable or refractory to treatment if the use of two or more appropriately chosen antiepileptic drugs ( aeds ) fails to adequately control seizures ." ], [ "before considering any changes to pharmacological treatment in a patient with refractory seizures , confirmation that the events are epileptic in origin is essential . it is estimated that up to 30% of patients seen in specialist epilepsy clinics present with non - epileptic attacks alone or in combination with epileptic seizures.21 in these patients , the prescription of aeds is often inappropriate and can lead to significant side effects , in addition to the financial burden to the health services . in many patients with refractory seizures ,", "this study showed that patients who were taking lamotrigine and valproate experienced an 83% reduction in seizures , whilst those taking the lamotrigine and carbamazepine or lamotrigine and phenytoin combinations experienced only a 43% and 34% reduction in seizures , respectively.37 these findings should be interpreted with some caution , however , as different doses of lamotrigine were used in each combination .", "a large study aiming to assess the efficacy of lamotrigine monotherapy also evaluated the effect on seizure control whilst taking lamotrigine as add - on to the first aed ( carbamazepine , phenytoin or valproate ) .", "other studies indicate that a combination of carbamazepine and valproate or carbamazepine and vigabatrin is more effective in seizure control than a combination of carbamazepine and phenytoin , although these studies were not controlled for drug concentration.35,36 the aed combination for which there is the most convincing evidence is lamotrigine and valproate .", "many of these drugs have novel or unknown mechanisms of action and demonstrate similar levels of efficacy and fewer side effects , less adverse pharmacokinetic drug interactions and are tolerated better by patients.25 when compared to carbamazepine in double - blind randomized control trials for treatment of partial onset seizures , gabapentin , lamotrigine and oxcarbazepine were found to have an similar efficacy but better levels of tolerability.2729 until recently , direct comparison studies in treatment - refractory epilepsy populations have been sparse . a recent systematic review and meta - analysis of studies on patients with refractory partial epilepsy suggested that topiramate and levetiracetam have a greater efficacy in controlling seizure frequency than the other new aeds.30 the same study found that gabapentin is likely to be less effective than other new aeds . in terms of tolerability , oxcarbazepine and topiramate were associated with significantly more withdrawals and therefore more poorly tolerated than the other new aeds ." ], [ "for resective surgery to be a viable option , the patient with treatment - refractory epilepsy should ideally have a single epileptogenic focus in a non - eloquent cortical region ( ie , not involved in key language , memory or motor processes ) .", "most epileptologists consider surgical management as second line therapy for patients with intractable seizures.39 this is especially true for patients with drug - resistant temporal lobe epilepsy ( tle ) , for whom temporal lobectomy can represent an effective treatment option .", "herbal treatments are generally viewed as alternative and complementary forms of medicine by both patients and physicians .", "however , only 15 patients were included and to our knowledge no follow - up study has been performed.84 the use of cannabis for epilepsy has been legalized in canada and licensed in 14 states within the united states , although it is prohibited in most european countries.85huperzine a. has been shown to be effective in animal models of epilepsy , and a clinical trial to assess its effectiveness has been planned.86,87 there is also laboratory data supporting the efficacy of kava ( piper methysticum ) and mistletoe ( viscum sp ) , but no clinical evidence exists to support their use . a number of other herbal treatments that are commonly used to treat seizures have either been shown to have no effect on the severity of seizures , or in fact demonstrate proconvulsant properties and exacerbate the condition .", "currently there are four main types of metabolic therapy in use for the reduction of seizures ." ], [ "for resective surgery to be a viable option , the patient with treatment - refractory epilepsy should ideally have a single epileptogenic focus in a non - eloquent cortical region ( ie , not involved in key language , memory or motor processes ) .", "although current evidence suggests that temporal lobe surgery is the most effective treatment option after the failure of two aeds , the same can not be said for other surgical procedures , such as frontal lobe resection , whereby the overall benefit from surgery may not be greater than trying alternative drug regimens . in these cases , the risks for each treatment option should be weighed up on a case - by - case basis until more definitive data is available to guide therapeutic decisions .", "most epileptologists consider surgical management as second line therapy for patients with intractable seizures.39 this is especially true for patients with drug - resistant temporal lobe epilepsy ( tle ) , for whom temporal lobectomy can represent an effective treatment option ." ], [ "patients with intractable epilepsy who are not suitable for epilepsy surgery or those who continue to experience seizures post - operatively may benefit from neurostimulation . this treatment option for patients with intractable epilepsy involves electrical stimulation of the nervous system using surgically implanted devices , or non - invasive stimulation as is the case for repetitive transcranial magnetic stimulation ( rtms ) .", "vagal nerve stimulation ( vns ) therapy is the only neurostimulation method to have received approval by the usa food and drug administration , whilst both vns and deep brain stimulation ( dbs ) are approved for use in patients with refractory epilepsy in the uk . in vns therapy , intermittent electrical stimulation", "the reduced thalamic blood flow that is observed in vns has been proposed to underlie the mechanism for seizure reduction.50 in addition to a number of retrospective studies , efficacy for this treatment option has been demonstrated in two randomized , placebo - controlled , double - blind trials , which reported a median seizure reduction of 24.5%28.0% in the group receiving high level vns compared to just 6.1%15.0% in patients receiving low level vns ( p = 0.01 and p = 0.04 , respectively).51,52 the risks associated with implantation of the vns device are relatively low , with a 3%5% chance of infection.5355 vocal cord dysfunction , throat discomfort , change in voice quality and sleep apnea can present post - operatively , and such consequences should be discussed with the patient when considering this treatment ." ], [ "furthermore , the diets are cost effective compared to many aeds.64 in practice , a median of 5 aeds are prescribed before considering a metabolic treatment such as the ketogenic diet.82 furthermore , 60% of child neurologists only use a ketogenic diet as a last resort treatment.83 it is therefore suggested that the metabolic treatments should be considered earlier in the course of treatment , especially in patients with refractory seizures who are not suitable for or willing to undergo resective surgery .", "currently there are four main types of metabolic therapy in use for the reduction of seizures .", "over the past century , the efficacy of dietary therapies for intractable seizures has increasingly been recognized .", "there is a body of evidence suggesting that metabolism - based therapy can be considered earlier in the treatment plan for patients with specific epilepsy syndromes .", "the classic ketogenic diet is a high fat and low carbohydrate diet that uses long chain fatty acids ( lcfas ) as its main source of fat ." ], [ "herbal treatments are generally viewed as alternative and complementary forms of medicine by both patients and physicians . there is , however , a small body of evidence demonstrating the effectiveness of some herbs at controlling seizures . out of all the herbal treatments , cannabinoids have the largest body of evidence supporting their use as anticonvulsants .", "in addition , much evidence is anecdotal , or when clinical studies have been performed , these often display poor methodology and do not have sufficient levels of statistical power to make firm conclusions from .", "further , good quality evidence in the form of controlled trials is required to justify the use of herbal treatments in a clinical setting ( see pearl et al for a comprehensive review).88", "however , only 15 patients were included and to our knowledge no follow - up study has been performed.84 the use of cannabis for epilepsy has been legalized in canada and licensed in 14 states within the united states , although it is prohibited in most european countries.85huperzine a. has been shown to be effective in animal models of epilepsy , and a clinical trial to assess its effectiveness has been planned.86,87 there is also laboratory data supporting the efficacy of kava ( piper methysticum ) and mistletoe ( viscum sp ) , but no clinical evidence exists to support their use . a number of other herbal treatments that are commonly used to treat seizures have either been shown to have no effect on the severity of seizures , or in fact demonstrate proconvulsant properties and exacerbate the condition .", "one randomized , double - blind controlled trial reported 50% of patients with secondary generalized epilepsy receiving cannabidiol becoming virtually seizure - free for the duration of the study ." ], [ "despite the fact that decisions to alter a treatment regimen may be influenced by local availability and funding , physicians should balance the evidence for efficacy in seizure reduction with the associated risks , side effects and patient preference .", "the fact that recurrent seizures and associated side effects from aeds significantly impact on patient s qol means that treatment decisions should be made in light of the best evidence for improved seizure control , enhanced qol and the greatest tolerability profile .", "confirmation that the events are epileptogenic in origin and early identification of an underlying etiology or specific epilepsy syndrome is essential to guide appropriate treatment for which syndrome or etiology specific efficacy exists .", "this may be in the form of monotherapy , polytherapy or alternative treatment options including surgery , neurostimulation , metabolic treatments and herbal remedies .", "patients with treatment refractory seizures continue to represent a large proportion of patients diagnosed with epilepsy ." ] ]

[ [ "in august of 2005 , hurricane katrina devastated the new orleans area with high wind , heavy rainfall , and a storm surge of about 7 m which caused the collapse of the levee system surrounding the city .", "residents who personally performed repairs of their properties as well as various skilled and unskilled laborers working in the construction and building maintenance trades were at risk for inhalation exposures to dust containing microbial and other agents during demolition , removal , and repair of flood - damaged and contaminated infrastructure and building materials [ 68 ] .", "approximately 80% of the city was flooded to varying depths for many weeks before the us army corps of engineers was able to implement temporary levee repairs and install emergency pumping capacity . in the aftermath of the flood event , the infrastructures of the city along with residences and commercial buildings", "as a part of a 5-year longitudinal study investigating the risk of respiratory illness associated with work in and around flood - damaged structures in post - hurricane katrina new orleans , baseline findings from initial cross - sectional survey are reported .", "the potential for respiratory illness arising from inhalation exposure to bioaerosols and microbial contaminants during restoration activities in the post - hurricane katrina environment was of particular concern .", "were grossly contaminated with sediments deposited by the floodwaters and subsequently by microbial overgrowth supported by the residual moisture , high humidity , and elevated temperatures in the area ." ], [ "the study cohort consisted of 791 adults residing or working in the greater new orleans metropolitan area .", "for the current hayfever compared to current trouble with pollen , grass , or fur , analysis indicated that the parallel question significantly enhanced the positive response rate for these symptoms ( 22% claiming current hayfever versus 39% claiming sensitivity to pollen , grass , or animal fur ; p < 0.0001 ) .", "it was based on a modified version of the standardized questionnaire reported by burrows et al . , which accounts for a variety of putative and established risk factors and potential confounders for the development of airways disease including asthma , allergic disease , historical confounding exposures , serious childhood respiratory illness , cigarette smoking history , environmental tobacco smoke , and age , gender , and race .", "similar but nonsignificant results were observed for ever and current asthma versus attacks of dyspnea and for chronic bronchitis versus copd . ", "was used in conjunction with the participant 's date of birth to determine whether asthma onset was after september 30 , 2005 ( post - katrina new onset asthma ) .", "the lln values were calculated by subtracting 1.645 see from the predicted values , where see was the standard error of the estimate and 1.645 is the 95th percentile of a standard normal distribution . those participants with chronic obstructive pulmonary disease ( copd ) were identified according to the gold criteria , that is , fev1/fvc % predicted less than 70% and fev1% predicted less than 80% ; however , only prebronchodilator lung function values were available and thus may not have adequately differentiated asthma ( with reversible obstruction ) from copd ." ], [ "statistically significant increases in prevalence odds ratio with restoration work time were observed only for transient fever and cough , for new onset sinus symptoms , and for dyspnea . when analyzed by logistic regression , the prevalence of fever and cough was statistically significantly associated with restoration work time , but only for men , with a prevalence odds ratio of 1.016 per 100 hours .", "likewise , for new onset sinus symptoms in men , the prevalence odds ratio was 1.042 per 100 hours .", "episodes of transient fever and cough occurring after hurricane katrina were reported by about 29% of the study cohort ." ], [ "the results of this study suggest moderate adverse impact on respiratory health from time spent in post - hurricane katrina flood restoration activities . published reports and public health surveillance systems generally did not show increases in emergency room visits or hospitalizations resulting from exposures in the post - hurricane katrina environment , although there have been a few reports of increased risk for respiratory effects . in a survey of 525 new orleans firefighters ,", "first responders would have had significant exposures to flood sediments and associated contaminants , in addition to microbial agents .", "finally , the reliance on self - reporting of respiratory symptoms and conditions could have led to misclassification due to recall bias ." ], [ "this study provides further evidence that workers performing restoration work on flood - damaged structures are at risk of respiratory health impacts from exposure to microbial - contaminated dust and debris .", "moderate adverse respiratory health effects including toxic pneumonitis and sinusitis were commonly reported in the study cohort , and the prevalence of new onset asthma among restoration workers was noticeably elevated . while it is unclear from this cross - sectional analysis whether restoration work exposures have adversely affected pulmonary function in the population , the functional parameters overall are depressed in the cohort .", "ongoing longitudinal health surveillance of this study cohort , along with a quantitative exposure assessment , will examine whether there is an increased risk for long - term or irreversible effects on respiratory health and how the risks relate to the nature and magnitude of the exposures occurring during posthurricane flood restoration work ." ] ]

[ [ "hence , this study aimed to determine the high - risk areas and spatially analyze the traffic crashes causing death to pedestrians in tehran in 2013 and 2014 .", "tehran is divided into 22 districts , 370 parishes , and 560 traffic zones , with more than 535 km of highway and 445 arterial streets ( 24 ) . \n", "\n road traffic injuries are responsible for the death of 1.23 million people around the world annually ( 1 ) . in terms of disability adjusted life year ( daly ( ( 1 ) .", "tehran is the largest city and the capital of iran , with an area of more than 612 square kilometers ( 22 ) .", "traffic load has dramatically increased in urban and suburban streets and roads of iran , while these transport infrastructures have not been developed qualitatively and quantitatively commensurate with car production . since a major proportion of traffic crashes in iran occur due to environmental factors , especially the quality of roads and streets and as the capacity of streets and roads , studying the urban and interurban roads and streets , particularly in densely populated cities with heavy traffic such as tehran , in terms of the environmental factors involved in traffic crashes can be helpful to more accurately identify the environmental factors of such crashes and their contribution .", "more than 20% of deaths caused by traffic crashes belong to pedestrians . according to the estimates ,", "pedestrians are associated with the highest contribution of deaths caused by traffic crashes in the world s densely populated cities ." ], [ "second , according to the universal transverse mercator ( utm ) , geographical coordinates of the traffic crashes locations with the accuracy of one to three meters were recorded and saved in a computer . the utm system divides the earth into 60 zones , each 6 of longitude in width and uses a secant transverse mercator projection in each zone .", "finally , global moran s index with euclidean distance method was used to study and analyze the distribution pattern of traffic crashes related to pedestrians in terms of being either cluster or scattered .", "the point of origin of each utm zone is the intersection of the equator and the zone 's central meridian . \n \n", "analytic surveys were conducted in the following steps : first , the exact location of traffic crashes causing death to pedestrians was extracted by reviewing the files of crashes in the database of tehran traffic police .", "z - score of this index shows that to what extent the studies feature has been distributed cluster - like , which may be statistically significant . in this study , this index was used to display the areas with high , low or moderate frequency of traffic crashes associated with pedestrians .", "moran s i index is the most common index used for measuring the spatial autocorrelation to determine how close are the objects compared to other close objects . \n \n" ], [ "low and high - risk traffic areas in terms of frequency of fatal crashes associated with pedestrians in tehran in 2013 - 2015", "distribution of fatal crashes associated with pedestrians in tehran by different months : 2013 - 2015 \n overall , 158 cases ( 79.8% ) of crashes have occurred in tehran highways .", "mapping of fatal crashes associated with pedestrians in the 22 districts of tehran in 2013 - 2015 \n result revealed that the density of events in the areas with dominant transportation , industrial and military land use was higher than the areas with dominant residential land use ( fig .", "\n one hundred ninety - eight incidents were studied ; 92 of which , ( 46.4% ) occurred in april 2013 to march 2014 and other 106 cases ( 63.6% ) occurred in april 2014 to march 2015 ." ], [ "\n the results of this study revealed that occurrence of the traffic crashes causing death among pedestrians in tehran during different months of 2013 and 2014 does not follow a specific and fixed trend .", ". \n \n results of this study revealed that high - risk traffic areas in terms of crashes causing death to pedestrians during the studied years are mostly located in the west and south of tehran .", "this study showed that about 80% of the studied crashes have occurred in highways and freeways .", "comparison of the statistics provided by the police and forensic medicine organization showed that the actual number of fatal crashes in tehran is more than those mentioned in the database of tehran traffic police and the information related to some crashes causing death does not exist in this database .", "therefore , it is not possible to acquire information on their location of occurrence through the police files . \n \n in such studies , it is better that the relevancy of the death of the injured by traffic crashes to these crashes be defined based on the time of death after crash ." ], [ "therefore , the majority of traffic crashes causing death to pedestrians have occurred on highways located at the main entrance ; that is , districts located in south , east and northwest of tehran .", "significant cluster - like distribution of crashes by the 560 traffic zones of tehran and existence of hot spots in terms of the studied crashes in the western and southern parts of tehran indicates the decisive role of environmental factors in occurrence of traffic crashes causing death to pedestrians .", "\n various districts of tehran , excluding central districts , are considered high - risk areas .", "moreover , it is necessary to organize the pedestrians traffic in high - risk areas . \n" ], [ "hosseini , the commander of tehran traffic police , personnel of crashes department of tehran traffic police , particularly lt .", "we would like to sincerely thank all who helped us in this study , especially gen .", "soroush , headquarters of public health faculty and members of the epidemiology department of shahid beheshti university of medical sciences .", "\n this study was part of a thesis conducted in shahid beheshti university of medical sciences ." ] ]

[ [ "the goal of our retrospective study of over 1361 patients was to compare the stone - free rates , steinstrasse formation , treatment efficacy and complications between patients with renal pelvic stones with and without pre - swl stent and to contribute to medical literature based on real life experiences .", ", pre - swl ureteral stent use should be preferred only in solitary kidney patients .", "since its first application in 1980 , extracorporeal shock wave lithotripsy ( swl ) has become the preferred treatment method in many ureteric and kidney stone diseases .", "the routine use of ureteral stent prior to swl is not recommended in renal stone cases despite the lack of any defined criteria in the guidelines [ 2 , 8 ] ." ], [ "this is a retrospective study conducted by scanning the medical data of 1378 patients treated with swl for renal pelvic stones at our clinic between 1995 and 2011 .", "the size of the stone was calculated in squared centimeters , by multiplying the widest width and length observed in kub . when multiple stones were observed , the sum of their sizes was calculated . in order to avoid statistical bias in this study ,", "seventeen patients who had percutaneous nephrostomy tube placement prior to swl were excluded from the study .", "the median age of the 1361 patients included in the study was 40 ( 1 - 85 ) years .", "the patients were separated into 3 groups based on the size of the stone : 1 cm ( group 1 ) , 1.12 cm ( group 2 ) , and > 2 cm ( group 3 ) .", "size of the stone(s ) , auxiliary procedures ( with or without stent use ) , radiologic evaluations at 3-month follow - up , and complications were evaluated retrospectively .", "patients were evaluated with kub and usg at the end of the first week after the procedure and at 3-month follow - ups ." ], [ "the grouping of 1361 patients according to the renal pelvis stone size was as follows : 514 patients in group 1 , 530 in group 2 , and 317 in group 3 .", "the average number of sessions was found to be significantly higher among the patients with stent placement in all groups ( group 1 : p = 0.022 ; group 2 and 3 : p = 0.000 ) , while the proportion of stone - free patients was similar across patients with and without stent placement in group 1 ( 86.4% and 73.3% ; p = 0.06 ) , a significant difference was observed in group 2 ( without stent 80.2% vs. with stent 56.8% ; p= 0.000 ) and group 3 ( without stent 75.1% vs. with stent 64.4% ; p= 0.047 ) .", "there were 178 patients ( 13% ) who had stent placement prior to the procedure according to the aforementioned criteria . the number of patients in groups 1 , 2 and 3 who had pre - swl stent placement was 30 ( 6% ) , 44 ( 8% ) , and 104 ( 33% ) , respectively . patient and stone characteristics by groups and stent placement are presented in table 2 , while treatment features by groups are shown in table 3 .", "while the rates of solitary kidney patients were significantly different across patients with and without stent placement in groups 1 and 2 ( p = 0.000 ) , no such significant difference was observed in group 3 ( p = 0.209 ) .", "according to these findings , no significant difference was observed between the patients with and without stent placement within the groups in terms of steinstrasse formation .", "of the 178 patients with stent placement , 68 ( 38% ) complained of frequent urination and pain in the bladder and kidney area that was associated with the stent but these issues were resolved via symptomatic therapies . \n " ], [ "ureteral stents are mostly used to enable continuation of drainage in the presence of complications such as stone , tumor or obstruction between the kidney and the bladder .", "use of ureteral stent in swl is generally not recommended and there are various studies on the matter .", "although ureteral stent is useful to prevent complications such as obstruction and renal colic following swl , it does not protect from steinstrasse formation or infectious complications and does not increase the proportion of stone - free patients [ 8 , 9 , 10 ] . in our study ,", "the retrospective nature , lack of randomization in terms of ureteral stent use prior to swl and that only 13% of patients had stent placement may be considered the limitations of this study .", "on the other hand , reported that the swl morbidity with or without stent placement is similar to that of pnl in patients with stones of > 2 cm ." ], [ "in our study , the stone - free rate following swl was found to be higher for renal pelvis stones > 1 cm in patients without stent placement , although no difference was observed regarding steinstrasse formation .", "our results showed that ureteral stents were observed to have a negative effect on the stone - free rates among stones greater than 1 cm in size .", "the results of this study support the idea of limiting the application of stents during swl and prevent possible complications as well as reduce the financial cost of treatment . considering that ureteral stents reduce stone - free rates", ", we believe that they should be preferred in special cases such as solitary kidney patients or those with long - term obstruction ." ], [] ]

[ [ "this systematic review was conducted to provide a comprehensive assessment of the association between the polymorphism in the gene tnfa -308g / a and the presence of t2 dm .", "noncommunicable diseases , including type 2 diabetes mellitus ( t2 dm ) , are considered the leading cause of death in the world and , in brazil , constitute the main cause of diseases .", "some facts corroborate the importance of heritability in t2 dm : the greater concordance between monozygotic twins than among dizygotic twins and a wide variation in the prevalence of t2 dm in epidemiological studies with different ethnic groups as well as positive results in numerous other genetic studies . in this regard", "withal , in most cases , a positive association between polymorphisms of these genes and t2 dm are not reproducible in the analysis of a different population .", ", it should be noted that even as more than 30 genes associated with t2 dm have been identified , the contribution of each individual gene in the disease susceptibility is very small .", "t2 dm assumes an important role in this context given that it is considered a worldwide epidemic disease ; in 2011 it appeared among the ten leading causes of death in the world and it is prospected that number of cases will continue to increase ." ], [ "any publications with case - control studies , on january 21 , 2016 , that show the relationship between polymorphisms of tnfa gene -308g / a and susceptibility to type 2 diabetes mellitus ( t2 dm ) were surveyed .", "inclusion criteria were as follows : ( 1 ) the study must have been case - control ; ( 2 ) the study should have assessed type 2 diabetes mellitus and -308g / a polymorphism of tnfa gene , even if associated with other comorbidities ; and ( 3 ) the study should have provided sufficient data , including the number or frequency of alleles and genotypes .", "the literature search was made through the virtual health library ( vhl ) which uses as bibliographic databases the publications found in sources such as lilacs , medline , and other information bases such as open educational resources , websites , and scientific events .", "studies were excluded if ( 1 ) there were commentaries , case reports , or non - case - control or meta - analyses studies ; ( 2 ) they did not report sufficient data ; ( 3 ) they presented data from other types of diabetes or did not specify what kind patients had ; and ( 4 ) they showed polymorphism in another coding region of the tnfa gene or ( 5 ) if the sample was composed of only dm patients .", "the filters are selected in accordance with the main subjects of the following terms : type 2 diabetes mellitus , tumor necrosis factor alpha , single nucleotide polymorphism , and genetic polymorphism .", "the following characteristics were collected : the authors , the study title , the year of publication , where it was published , the sample size , the tnfa -308g / a genotypes with their corresponding simple frequencies and percentages for the control and the case group , and the study 's p value and odds ratio , when calculated .", "the search terms used were as follows : diabetes and tnf or tumor necrosis factor , and polymorphism .", "data from eligible studies were extracted independently in accordance with the inclusion and exclusion criteria . for each study" ], [ "the literature search found articles published starting from 2000 , given that the year the complete mapping of the human genome was made available .", "advances in molecular biology technology since this project have been quick and , thus , increasing the number of genetic studies published for the association of certain genetic polymorphisms with various pathologies . in the case of literature search for articles with case studies that related polymorphism position -308 of the tnfa gene with diabetes ,", "due to contradictory results , this systematic review is aimed at providing a comprehensive assessment of the association between tnfa -308g / a and phenotype involving type 2 diabetes .", "the general characteristics of the studies included in this review are summarized in table 1 . in three studies conducted in spain , hungary , and", "morocco significant associations between the tnfa -308g / a polymorphism and the risk of t2 dm were identified [ 11 , 17 , 20 ] : two of them in patients with other comorbidities such as coronary heart disease and atherosclerosis . in the present study , therefore , we infer that although there was no evidence of heterogeneity in the association between polymorphisms in the tnfa -308g / a gene and increased risk for development of t2 dm , the presence of positive results may mean that few studies have not been enough to clarify this relationship , and besides there is no documented evidence in various ethnic groups .", "two of these studies did not show enough genetic data for analysis . in relation to tnfa gene ," ], [ "this evidence supports the assumption that polymorphisms in the tnfa gene and its association with other aspects , both genetic and environmental , may represent an important risk factor for type 2 diabetes mellitus .", "several association studies have discussed the importance of clarifying the relationship between genetic polymorphisms and the development of type 2 diabetes .", "several studies with the frequency of genotypes in control and case group were observed for a better understanding of the population genetic profile and a possible association between polymorphism of tnfa gene and t2 dm in groups with different ethnicities .", "studies seeking interactions between these variations , in particular , have been very promising . in the case of diabetes , a syndrome whose etiology is complicated and involves several risk factors for its development and progression , some studies on single nucleotide polymorphisms were suggested as causing the phenotypic characteristics and responsible for the increased risk of developing pathology [ 2527 ] . to study the risk factors for a disease is to study the possibility of a certain event happening . within the epidemiological concepts ,", "linkage research studies genetic markers and specific polymorphisms in a family group that has the disease ." ], [ "even though these factors may not be changed , the identification of their presence in individuals and families may enable health professionals to advise change in the lifestyle of these patients , avoiding early manifestation of t2 dm .", "risk factors not modifiable or irreversible in nature , such as genetic profiles , refer to the individual characteristics ." ] ]