Spinal cord injury is a life-transforming condition of sudden onset that can have devastating consequences. A multidisciplinary, functional goal-oriented programme is required to enable the tetraplegic patient live as fully and independently life as possible. Physiotherapy is a very important part of the multidisciplinary team required to prevent many of the immobilization complications that may result in serious functional limitations, reduce overall morbidity and achieve well patterned recovery. This study therefore highlights the neuromuscular adaptations of tetraplegic patients to physiotherapy over a period of six weeks. Fifteen patients participated in this study and the results showed that even though changes in the musculoskeletal parameters are inevitable in tetraplegics, the extent/degree of reduction of these parameters was grossly minimized in the studied subjects through the administration of physiotherapeutic measures. However, further research using a large sample size will be required to evaluate the physiologic adaptations of the neuromuscular system to the physiotherapy interventions among patients with spinal cord injury. Spinal cord injury (SCI) is a life transforming condition with a great risk of development of an array of debilitating and potentially life- threatening complications . Its cliTetraplegic patients have impairment of motor and/or sensory function in the cervical segment of the spinal cord . Tetraplwww.spinal-injury.net).The post traumatic dysfunction of the spinal cord causes loss of homoestatic and adaptive mechanisms which keep people naturally healthy. There are diverse causes of SCI but any mechanism that causes injury to the vertebral column or the bones in the back can damage the spinal cord. These causes can be traumatic (84%) or non-traumatic (16%) . The mosTraumatic spinal cord injury (SCI) in the UK affects an estimated 10–15 people per million population per year so there are around 40,000 individuals in the UK living with a traumatic SCI . The estBielby and Joint contractures or permanent limitations of joint movement usually due to poor positioning, lack of movement and/or muscle spasticity; muscle atrophy, a shrinking or wasting of musculature due to lack of use; osteoporosis, deterioration of the bone that may occur due to decreased weight bearing, as well as factors related to the injury itself; development of deep venous thrombosis and possible pulmonary embolism due to lack of or reduced muscular pump activities for adequate venous return resulting from paralysis or weakness of muscles; and decreased respiratory function which can create such problems as increased risk for respiratory infections, congestion, rapid breathing and/or increased shortness of breath.Management of the tetraplegic patients requires a multidisciplinary team approach, physiotherapy being one of the major inputs required in the care. Physiotherapy commences as soon as the patient is admitted and he/ she is stable clinically. The main objectives of physiotherapy in the acute phase include prevention of the above listed risks, maintenance of full range of motion (ROM) of all joints within the limitations of the injury, maintenance/ strengthening of all innervated muscle groups and to monitor neurological status and manage appropriately .Comprehensive rehabilitation (physiotherapy as a key part) along with early surgery, where necessary, is believed to markedly reduce the overall morbidity of spinal cord injured patients by enabling the patient to lead an independent life .Physiotherapeutic inputs have been considered an important adjunct in the care of the tetraplegic patients following spinal cord injury but no study has systematically and subjectively documented to what extent these measures or inputs maintain and improve functions towards eventual mobilization of tetraplegics after the acute care. This study therefore aims to fill this gap in knowledge.The following research questions were raised to guide the study.Would physiotherapeutic inputs achieve the expected goals in the recovery pattern / trend of tetraplegic patients? Specifically, the investigation probed into whether there would be a maintenance or improvements in the muscle strength, muscle girth, and range of movement among tetraplegic patients following physiotherapy measures in the acute phase of their management?The following hypotheses were formulated and tested.Physiotherapeutic inputs would not significantly contribute positively towards mobilization of spinal cord injured patients with tetraplegia during the acute phase of their management.The specific hypothesis formulated and tested was whether there would be no significant improvements in the muscle strength, muscle girth, and range of movement among tetraplegic patients following physiotherapy measures in the acute phase of their management.Fifteen subjects participated in this study which comprised of thirteen (13) males and two (2) females with average ages of 29.3 and 37.0 years old respectively. They were randomly selected from those admitted in the neurosurgical ward of the University of Benin Teaching Hospital, Benin City, Nigeria, between 2009 and 2011. The age range of the males was between 12 and 50years old while that of the females was between 27 and 47 years old.Inclusion criteria was the enrollment of patients with quadriplegia resulting from SCI  without associated injuries like head injuries, psychiatry condition, fractures of the limbs or ribs; medical conditions like diabetes mellitus and positive retroviral states. Exclusion criteria included aged patients of over 65years old and those with chronic (old) SCI. Ethical approval of the research and ethics committee of the study institution was sought and obtained.This study measured musculoskeletal parameters of fifteen (15) tetraplegic patients at the commencement of physiotherapy immediately at their being admitted to the neurosurgical ward, two weeks, four weeks and six weeks post admission. The progress or otherwise on the specified variables during the period of immobilization were compared. Physical measurements of these parameters were taken using validated instruments at the different stages of care.The present physiotherapeutic measures employed in the management of SCI patients with tetraplegia were Chest Physiotherapy, Passive Mobilization, Proper Positioning on bed, strengthening exercises, soft tissue mobilization, pain management procedures and preparation for mobilization.Parameters that were measured adapted Adams and Hamblen’s (1990) protocol which focused on muscle strength, muscle girth, range of joint movements/motion, forced expiratory volume and maximum inspiratory volume/capacity. Muscle strengths were measured subjectively using Medical Research Council grading as follows: 0= no contraction; 1= a flicker of contraction; 2= slight power, sufficient to move the joint only with gravity eliminated; 3= power sufficient to move the joint against gravity; 4= power to move the joint against gravity plus added resistance; 5= normal power .Muscle girths were measured using measuring tape rules. The girths of arms, forearms, thighs and legs were measured in these patients using the International Standards for Anthropometric Assessment (ISAK) recommended points and positions. The bilateral arm girth measurements were taken at the level of the mid acromiale-radiale with the patients assuming a relaxed supine lying position and the elbow being in an extension with the tape positioned perpendicular to the long axis of the arm.The forearm girths bilaterally were taken at the maximum girth of the forearm distal to the humeral epicondyles with the forearm supinated while relaxing the muscles of the forearm. For consistency in the measurement, a point 10cm away from the tip of the olecranon was marked as the reference point. For the thigh and leg girths measurements, a distance of 12.5cm above and below the upper and lower tips of the patellae was used as the reference point for the purpose of uniformity. The patients were measured in a relaxed supine lying position with the knee joints extended. In all the girth measurements, it was ensured that the tape was firmly passed round the limbs without excessive tension and that it did not indent the skin or slip. Three measurements were taken on each point and the average values of the measurements were taken and recorded.The joints range of motion of all the patients were measured with the aid of a goniometer. The joints used in this study were the shoulders, elbows, wrists, hips, knees and ankle joints bilaterally. Measurements were also taken at two, four and six weeks on admission.The neurosurgical management of a tetraplegic compulsorily requires a period of six weeks of immobilization on bed for postural reduction. Tetraplegic patients admitted in the neurosurgical ward in supine lying positions with either a cervical collar  or Crutchfield tongs/calipers or Gardner-Wells traction fixed on the skull depending on the degree of instability to immobilize the injured cervical spine for spinal stabilization were immobilized on bed for an average of six weeks. A few of the patients with unstable spine or observed not to have improved satisfactorily with conservative approach were operated upon using surgical procedures for spinal stabilization. In such an instance, they spent less than six weeks on bed post operation for proper spinal stabilization and rehabilitative care. All the patients had daily physiotherapy during the acute phase of their management. The daily treatment consisted of manual therapy of Chest Physiotherapy of vibration and shaking of the chest for about 5- 10minutes along with active deep inspiration exercise. Passive mobilization of all the extremities of the patients carried through safe range or degree, strengthening exercises all the muscles of the extremities, soft tissue mobilization with aid of talcum powder, proper positioning of the limbs on bed, pain management procedures and preparation for mobilization in the form of ambulation when due. The treatment regimen takes an average of one hour per patient daily and each patient had four treatment sessions per week. The treatment period was six week of postural reduction on bed. The data obtained were fed into SPSS version 16 statistical analysis. Descriptive statistics of mean, standard deviation and percentage as well as inferential statistics of one-way repeated measures ANOVA were used to test the hypotheses at alpha level of 0.05.The results are presented in tables In terms of inferential statistics using one-way repeated measures, three out of sixteen parameters were not statistically significant. Specifically, In The second and third measurements for right upper limb, below elbow, showed statistically significant values of 16.783 with 0.058 and 7.647 with 0.058 respectively as shown in The purpose of this study was to investigate effect of early physiotherapy measures on musculoskeletal parameters  that are required for functional activities in patients with spinal cord injury (SCI).The outcome of the study revealed significant differences in the muscle girth measurements in majority of the body segments of the extremities of the patients measured. The study revealed no significant difference in the reduction of the chest circumferential measurements taken two weeks on admission but a significant difference in the increase in the circumferential measurement obtained by six weeks during rehabilitation. However, there were significant differences both in the initial reduction and the eventual increase in the waist circumferential measurement of the patients during the six weeks period of admission for postural reduction. The chest and waist circumferential measurements were used as surrogates for chest and abdominal muscle strength and lung ventilation capacity (inspiratory and expiratory functions) in this study. Respiration is a function that is critical for sustaining life but also significantly important for generating the pressure needed to cough, speak, and swallow . RespiraTurning and positioning are measures that can minimize spasticity and prevent flexor muscle hypertonia in SCI patients who are recumbent on bed. The study also recorded full range of motion on all the joints of the extremities measured throughout the study period. This has been achievable through the daily administration of passive mobilization of the limbs by the physiotherapists. Contractures (reduced joint mobility) were due to loss of extensibility in soft tissues spanning joints, and were found to be a common complication of spinal cord injury. One study found that spinal cord injured patients had, on average, seven contractures at between 6 and 7 weeks after injury . ContracIn the present study, occurrence of pain was anticipated and was also prevented by the use of medications by the neurosurgeon to avert occurrence of chronic pains. Topical analgesic gels were also applied on the joints of the upper and lower extremities to relieve pain where applicable. These were gently massaged into the joints by the physiotherapists; patients’ relatives were taught how to apply these gels where necessary in order to ensure twice or thrice daily applications when the severity of pain demanded such.This study has presented results that further strengthened the effects of physiotherapeutic measures as important adjuncts in the management of SCI patients with tetraplegia especially during the acute care phase of management. It showed that even though changes in the musculoskeletal parameters are inevitable in tetraplegics, the extent/degree of reduction of these parameters can be reduced grossly through the administration of physiotherapeutic measures. It was evident from the results that the rate of neurophysiological responses that follow the spinal cord injuries which result in deterioration of neuromuscular parameters like the muscle mass, tones, power and joint flexibility can be greatly influenced by application of physiotherapy techniques and measures. Therefore, it is highly recommended that structured physiotherapeutic measures should be an adjunct to the care and management of SCI patients. It is also recommended that further studies that will make use of larger samples and that will also follow up effects of physiotherapeutic measures on recovery pattern of patients with SCI beyond the acute stage be conducted.


Suggestion has been defined as a form of communicable ideation or belief, that once accepted has the capacity to exert profound changes on a person's mood, thoughts, perceptions and behaviors . The hypnotized individual will be concentrating on the hypnotist's voice relaying a series and variety of suggestions to which the individual may or may not respond. Under the influence of hypnotic suggestion (or post-hypnotic suggestion which is a suggestion given under hypnosis but activated post-hypnosis) the experience of pain  suggests that placebo effects require the involvement of the prefrontal cortex whereas hypnotic suggestibility is increased when the prefrontal cortex is hypoactive. Applying TMS to the left dorso-lateral prefrontal cortex (DLPFC) to impair function in this region results in increased hypnotic suggestibility  matter microstructure and hypnotic suggestibility (Hoeft et al., The PFC is a large region of the brain, and one might consider the role of different regions of the PFC in the varieties of suggestion. The involvement of the DLPFC could differentiate hypnosis and placebo effects. The role of more ventromedial regions in other forms of suggestion (Asp et al., Lifshitz et al.  draw a dNotably, research suggests that measures of placebo suggestibility do not correlate with hypnotic/imaginative suggestibility measures (Kihlstrom, In conclusion, whilst there are potentially informative similarities between hypnotic suggestion and placebos, their differences, particularly with regard to the differential contributions of regions of the prefrontal cortex, are also potentially informative as to the nature of suggestion more generally.The author confirms being the sole contributor of this work and approved it for publication.This research was supported by Bournemouth University.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


European Commission and Patients Associations identify Registries as strategic instruments to improve knowledge in the field of Rare Diseases ,2. InterIn this study, exploratory data analyses were applied to the EPIRARE (European Platform for Rare Diseases Registries) Registry Survey in order to generate a macro-classification and characterization of RDPR and to deepen different informative needs.At first, a Multiple Correspondence Analysis (MCA) suggested associations between selected variables characterizing the structure of RDPR Figure . Then, aThese results, identifying different profiles of RDPR and specific informative needs, represent an informative support aimed at addressing the activities for the design of an European platform of Rare Diseases. Identification of informative cores could address the activities of a platform able to enhance the sharing of information between RDPR with common aims, but also to facilitate a coherent dialogue between RDPR with different profiles.Guide to interpretation: the arrows indicate the directions of association among the aims; the dimension of the circles represents the frequency of the variable. The higher are the coordinate and the frequency of the variable, the more it contributes to the interpretation of the factorial axis; variables placed on the same direction are correlated.


Despite a wealth of fossils of Mesozoic birds revealing evidence of plumage and other soft-tissue structures, the epidermal and dermal anatomy of their wing’s patagia remain largely unknown. We describe a distal forelimb of an enantiornithine bird from the Lower Cretaceous limestones of Las Hoyas, Spain, which reveals the overall morphology of the integument of the wing and other connective structures associated with the insertion of flight feathers. The integumentary anatomy, and myological and arthrological organization of the new fossil is remarkably similar to that of modern birds, in which a system of small muscles, tendons and ligaments attaches to the follicles of the remigial feathers and maintains the functional integrity of the wing during flight. The new fossil documents the oldest known occurrence of connective tissues in association with the flight feathers of birds. Furthermore, the presence of an essentially modern connective arrangement in the wing of enantiornithines supports the interpretation of these primitive birds as competent fliers. Exceptional fossil preservation allows access to crucial information regarding the integumentary structures244457911The distal wing of MCCMLH31444 is likely exposed in ventral view, as evidenced by the presence of ventral flexor depressions in the exposed side of the pre-ungual phalanges of digit I and II and the metacarpal II15Confuciusornis sanctus101010Three epidermal structures  indicate that the connective tissues of MCCMLH31444 are mainly preserved as calcium phosphate while the plumage has likely undergone a carbonization process . PhosphaThe parallel pattern of plait-like fibers alternating with an unorganized matrix in MCCMLH31444 is characteristic of modern tendons and ligaments that are subject to multidirectional mechanical stresses1919229Ligg. phalangoremigalia distalia, digitationes remigiales999In modern birds, networks of smooth muscles attached by elastic tendons to the outer walls of feather follicles control the coordinated movement of groups of feathers91024The evolution of the modern network of smooth muscles, elastic tendons and ligaments involved in the function of the wing’s flight feathers was a paramount event in the fine-tuning of aerodynamic capabilities in birds. By allowing these feathers to be repositioned in tandem, this sophisticated dermal system helped the wing to maneuver as a single functional unit and to cope with the strenuous aerodynamic stresses of flapping flight. The 125-million-year-old MCCMLH31444 provides the oldest reported evidence of this intricate connective network and its earliest phylogenetic occurrence. The remarkably modern anatomy and arrangement of the connective tissues preserved in the wing of MCCMLH31444 implies that Early Cretaceous enantiornithines had already developed forelimbs morphologically well adapted for flight, losing most of the primitive grasping functions attributed to the dinosaurian forerunners of birdsProtopteryx fengningensis4418418Although still showing a suite of primitive skeletal traits4How to cite this article: Navalón, G. et al. Soft-tissue and dermal arrangement in the wing of an Early Cretaceous bird: Implications for the evolution of avian flight. Sci. Rep.5, 14864; doi: 10.1038/srep14864 (2015).


Manualised Family Based Treatment (FBT) is considered the best evidenced treatment for adolescents with Anorexia Nervosa. However, the replication of outcome data from research trials into treatment in a general clinical setting can be a challenge. Following on from the presentation entitled 'Overcoming challenges of implementation of FBT at the Regional Eating Disorders Service (REDS) in Auckland, New Zealand', the results of the implementation of the delivery of FBT at Auckland's Regional Eating Disorders Service (REDS) are presented. Results are based on a clinical audit of treatment outcomes in the year preceding the implementation of FBT. Data will be presented of the period of 18 months while FBT was established, and the 6 months afterwards. A comparison of these different periods will be made with respect to weight recovery and psychometrics as well as effects on length of admission and re-admission rate to the paediatric hospital.Service Initiatives: Child and Adolescent Refeeding and FBT stream of the 2014 ANZAED Conference.This abstract was presented in the


According to World Health Organization (WHO), dental caries is common among 60-90% of school children and nearly among 100% of adults. Further, severe form of periodontal disease is found in 15-20% of 35-44 years old patients. WHO experts emphasize that timely prevention of dental diseases will not only contribute importantly to mainitaining oral health but would also significantly reduce cost of care and treatment of oral diseases.An important component in the prevention of oral diseases is informing of patients about the possibility of maintaining oral health with the help of available oral hygiene products. For adequate and efficient planning of activities to raise oral health awareness it is necessary to estimate level of oral health literacy of the community. In different countries there are certain questionnaires which are primarily used during scientific research. Many of these questionnaires and tests are not well-suited for use in patients with different culture and language.We suggest that standardization of oral health literacy assessment would be conducive to more effective evaluation of oral health care needs of a given population. Thus, we have developed an index of oral health literacy which has the following characteristics:- questions are universal and reflect current trends of prevention of oral diseases;- questions have no cultural contexts and attachments;- questions can be translated into any language;- questions have some variants for answers;- quantitative assessment of oral health literacy.Pilot studies showed that the developed index of oral health literacy can reliably predict the level of knowledge in young patients and the state of the oral health.In conclusion, the use of the developed index should will allow assessment of oral health literacy of patients regarding aspects of oral health preservation irrespective of nationality and language should facilitate the development of personalized approaches to prevention of dental diseases.


Controlled Clinical Trials are the Gold Standard to assess the efficacy and safety of a new therapeutic intervention. Furthermore, their results are used to make decisions in relation to public health issues. This stAll trials led by CENCEC from 1992 to 2013 were characterized according to specific variables. A review of available information at the Cuban Regulatory Agency regarding the registration process of new drugs was performed. Interviews to sponsors, clinical investigators and health authorities were carried out to identify products registered outside the country, health benefits and impact of the results of clinical trials conducted by CENCEC.In this period, 133 clinical trials were completed evaluating 58 products from 28 sponsors, with participation of 1075 clinical sites from 90 hospitals and 60 primary care health care units involving 4241 researchers. Some of those studies were performed for the evaluation of health technologies and to search evidence for public health decisions. The activities of CENCEC were carried out according to international standards: Quality Assurance System Certificated (ISO 9001:2008), Cuban Public Registry of Clinical Trials (WHO Primary registry [The benefits of "new intervention" clinical trials were related to morbidity and mortality rates, new patterns of disease management, better Infrastructure of clinical sites, improvement of the quality of medical care, the introduction of new technologies and the building of capacity of clinical investigators .The experience of Cuba, a low income country with a defined health policy, shows that the results of clinical trials are an effective tool to improve health services and for an efficient introduction of evidence in medical practice, for decision making in public health leading to improvements in clinical care. The experience gained could be applied in other countries of Latin America to achieve public health results .


The aim of the present study was to determine different affections of the salivary ducts in buffaloes with special reference to diagnosis and treatment. The study was carried out on 39 buffaloes suffering from different affections of the salivary ducts. The recorded affections of the salivary ducts in buffaloes include; ectasia of the parotid duct (21 cases), parotid duct fistula (15 cases) and sialocele (3 cases). Each case was subjected to full study including case history, clinical examination, diagnosis, and treatment whenever possible. Exploratory puncture and radiography were used for confirmation of diagnosis. Intraoral marsupialization was performed for treatment of parotid duct ectasia. Salivary fistula was corrected by one of two successful techniques; the first by reconstruction of the parotid duct and the second by ligation of the parotid duct just caudal to the fistula opening. Sialoceles were corrected by removal of the mandibular salivary gland of the affected side. The main salivary glands in buffaloes consist of three pairs namely; parotid, mandibular and sublingual glands.et al., 1988).The parotid duct emerges from the distal extremity of the gland and courses forward along the ventral border of the masseter muscle, then turns upward and gains the rostral border of the muscle. After a short course, the duct opens into the buccal vestibule at the parotid papilla .The sublingual duct originates from the rostral extremity of the gland and courses deeply with the mandibular duct until it opens alone or into a common duct with the mandibular duct at the sublingual caruncle .The common affections of the salivary ducts in buffaloes were recorded in the available literatures. They include; ectasia of the parotid duct, salivary fistula, sialolith and sialoceles . Three affections of the salivary ducts were recorded in the present study namely; ectasia of the parotid duct, parotid duct fistula and mandibular sialocele.Ectasia of the parotid duct was diagnosed in 21 animals aged 4 months to 8 years. 15 animals were females and 6 were males. Diagnosis was established depending on the case history and clinical symptoms. Exploratory puncture and radiographic examination were used for confirmation of diagnosis. Marsupialization was the treatment of choice and was performed under the effect of the tranquilizer xylazine HCl 2% with a dose rate of 0.05 mg/kg intramuscularly.et al., 1991). The second technique was applied in 9 animals and was performed by ligation of the salivary duct just caudal to the fistula opening under the effect of xylazine HCl 2% at a dose rate of 0.05 mg/kg intramuscularly  with subcutaneous local infiltration analgesia using 10 ml of lidocaine HCl 2% at the site of operation.Parotid duct fistula was diagnosed in 15 female buffaloes aged 2 to 8 years. Diagnosis was established depending on the presence of an opening along the course of the parotid duct discharging saliva. The condition was corrected by two techniques. The first one was applied in 6 animals and was performed by the application of a segment of polyethylene tube at the site of fistula for reconstruction of the patency of the salivary duct  were applied with 2 cm distance between them and tied after withdrawal of the probe. After that, the skin wound was closed using simple interrupted stitches (# 2). Also, the site of fistula opening was freshened and trimmed followed by simple interrupted silk stitches. Sialocele was recorded in 3 adult buffaloes .A soft fluctuating painless swelling was detected at the mandibular space since a few months as per the case history. No case history was established explaining the beginning of the condition except a gradual appearance and enlargement of the swelling. Exploratory puncture revealed the presence of saliva and aspiration of the cystic swelling resulted in its collapse but refilling was detected within one hour or more.Treatment was performed in only two cases, where unilateral removal of the mandibular salivary gland of the suspected affected side was performed in both cases. Recovery was uneventful in two cases and the third one was not operated at owner’s request.Salivary ducts carry a huge amount of saliva from the salivary glands to the mouth cavity. Anatomically, the parotid salivary duct runs mostly subcutaneously along its course while mandibular and sublingual salivary ducts are embedded in tissues except at their terminal parts where they run submucosally inside the mouth cavity.et al., 1991). Sialoceles occurs due to leakage of saliva from the injured mandibular or sublingual salivary ducts . Intraoral trauma may cause the formation of sublingual or mandibular sialoceles . Diagnosis of salivary duct affections was performed depending on clinical presentation of all cases; however a degree of confusion may be present in the differential diagnosis between ectasia of the parotid duct and sialoceles  and formation of a cystic swelling at one side of the head. However, the presence of parotid duct ectasia in calves may have a congenital link . Salivary fistula of the parotid duct was corrected successfully by reconstruction of the duct using a segment of polyethylene tube or by destruction of the gland through ligation of the duct just caudal to the fistula opening. Selection of either technique was based on the surgeon’s preference.Complete reconstruction of the affected parotid duct in cases of parotid duct ectasia was performed in one buffalo with successful results. However, complete resection of the dilated duct and its replacement by a polyethylene tube is a tedious operation and should be performed only under general anesthesia .The presence of sialoceles at the middle of mandibular space does not reveal the affected side. However sialography using contrast medium will help in differentiation of the healthy side from the affected side .The main affections of the salivary ducts in buffaloes are two; ectasia of the parotid duct and salivary fistula of the parotid duct while the third affection is mandibular sialoceles which occurs only sporadically. Fortunately, both common affections can be corrected easily, safely and in a short time without postoperative complications and with good prognosis.


Cancer is one of the most urgent health issues of today. According to WHO, the number of cancer cases is expected to increase by 75% in the next two decades . DespiteThe aim of any anti-cancer treatment is to selectively kill cancer cells by targeting key biological properties essential for the maintenance of tumorigenicity and malignant progression . CurrentA newer type of anti-cancer therapy generally called molecularly targeted therapy relies on rationally designed agents to target, with a high degree of specificity, well-defined molecules or pathways that operate in cancer cells to maintain their malignant potential. Although both cytotoxic and molecularly targeted therapeutic approaches generally exploit differences between neoplastic and normal cells, only targeted therapies enable the so-called precision medicine. Recent advances in the field of molecular profiling have opened up a real possibility to make better informed treatment decisions based on the data from personalized tumor profiling . HowNew generation sequencing methodologies while enabling to identify genomic alterations associated with different types of cancer with an unprecedented completeness also revealed the high degree of genetic diversity existing not only between different types of cancer but also between individual tumors of the same histotype . A These considerations are of particular relevance in the context of the CSC hypothesis, which postulates that CSCs constitute only a minor fraction of tumor cells capable of initiating tumor growth . Inde novo and recurrent AMLs, it was established that a minor AML clone underrepresented in the primary tumor became dominant in recurrent tumors as a consequence of chemotherapy  heterogeneous types of cancer cells can be separated spatially within a tumor raises several important questions concerning the identity of tumor clones that are capable of escaping from anti-cancer treatments and repopulating the tumor. There is some evidence that exposure to therapy may influence the dynamics of clonal repopulation and lead to the alternation of clonal dominance as a consequence of treatment. For example, by applying next generation sequencing to compare somatic mutations in matched pairs of otherapy . Similarotherapy . In the in vitro might be more feasible. Such an approach has the advantage of reducing the variability in treatment conditions and dissecting the effects of single and combined treatments. By comparing treatment responses in different types of cancer cells from the same tumor should allow to improve predictions on the efficacy of a particular treatment scheme in a particular tumor.The realization that intratumor heterogeneity poses one of the major challenges to overcome resistance to anti-cancer therapy raises a number of questions: are there common molecular denominators underlying resistance to different types of therapy? Is there an interaction between different populations of cancer cells residing in the same or different geographic regions of the same tumor? What is the impact of different types of anti-cancer therapy in the emergence of resistant clones? To address these issues, there is a need of suitable methodologies that would take into account the spatiotemporal patterns of intratumoral diversity. It has been proposed that multiple sampling analyses of multiple regions from matched pairs of untreated and recurrent tumors would be required to assess the impacts of intratumoral diversity on the development of resistance to anti-cancer therapies . Such anIt should be noted that the degree of intratumoral heterogeneity may not necessarily reflect an enhanced malignant potential. It is believed that a considerable portion of new mutations arising in the course of tumor evolution are passenger mutations . In suchThe emerging scenario of recurrent tumor growth reveals key roles of intratumoral heterogeneity in intrinsic and acquired resistance to cytotoxic and targeted therapies. Understanding spatiotemporal patterns and dynamics of intratumoral heterogeneity before and during therapy is crucial for the ability to design individual-tailored treatment regimens best suited to a particular molecular context.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.


Gram- negative bacteria utilize a diverse array of multidrug transporters to pump toxic compounds out of the cell. Some transporters, together with periplasmic membrane fusion proteins (MFPs) and outer membrane channels, assemble trans-envelope complexes that expel multiple antibiotics across outer membranes of Gram-negative bacteria and into the external medium. Others further potentiate this efflux by pumping drugs across the inner membrane into the periplasm. Together these transporters create a powerful network of efflux that protects bacteria against a broad range of antimicrobial agents. This review is focused on the mechanism of coupling transport reactions located in two different membranes of Gram-negative bacteria. Using a combination of biochemical, genetic and biophysical approaches we have reconstructed the sequence of events leading to the assembly of trans-envelope drug efflux complexes and characterized the roles of periplasmic and outer membrane proteins in this process. Our recent data suggest a critical step in the activation of intermembrane efflux pumps, which is controlled by MFPs. We propose that the reaction cycles of transporters are tightly coupled to the assembly of the trans-envelope complexes. Transporters and MFPs exist in the inner membrane as dormant complexes. The activation of complexes is triggered by MFP binding to the outer membrane channel, which leads to a conformational change in the membrane proximal domain of MFP needed for stimulation of transporters. The activated MFP-transporter complex engages the outer membrane channel to expel substrates across the outer membrane. The recruitment of the channel is likely triggered by binding of effectors (substrates) to MFP or MFP-transporter complexes. This model together with recent structural and functional advances in the field of drug efflux provides a fairly detailed understanding of the mechanism of drug efflux across the two membranes. Multidrug resistance or polyspecific transporters (MDRs) are present in all living systems. However, they are particularly abundant and diverse in bacteria and comprise 2–7% of the total bacterial protein content  are primary active transporters which couple substrate translocation with binding and hydrolysis of ATP. MDRs in all the other superfamilies are secondary transporters which utilize electro-chemical gradients of ions (most frequently protons but sometimes sodium) to transport their diverse substrates. Both primary and secondary transporters are ubiquitous in bacteria, however their relative presence seems to correlate with energy generation: fermentative bacteria tend to rely more on the primary transporters while genomes of aerobic bacteria contain somewhat more secondary transporters  binding of a substrate on the cytoplasmic or periplasmic side of the membrane, (ii) conformational changes in a transporter leading to re-orientation of the binding site to the other side of the membrane, and (iii) the release of the substrate. The conformational change leading to reorientation of substrate binding sites and relaxation of a transporter are usually energy-dependent steps, which is provided by either ATP hydrolysis (ABC pumps) or by a proton motive force (PMF) or sodium motive force. The basic mechanism of energization of transporters by ATP and PMF are well understood on examples of ABC and MF transporters  and the outer membrane channels (OMFs)  which are largely responsible for the low permeability characteristic , ABC  and MF  superfamilies  showed significantly lower affinity to AcrB  by stimulating the efflux activities of transporters and (ii) by engaging OMFs and opening them for substrates to be expelled from the cell  that interact with transporters within the cytoplasmic membrane , the MFP oligomerization was treated more as an artifact of crystallization, partly due to the fact that hydrodynamic studies and the size exclusion chromatography studies showed only monomers in solution   in the transport could be enhanced by additional subunits? In case of MFPs, this could be the separation of roles in the stimulation of a transporter and the recruitment/opening of OMF. In transporters, this could be an added substrate specificity or a separation of energy transduction and substrate translocation as suggested for MdtBC  to identify MFP-transporter and MFP-OMF molecular interfaces that are critical for activation of efflux and (ii) to characterize conformational transitions in all components of the complexes leading to efflux across the outer membrane. Non-typical transporters could be powerful tools in understanding how the trans-envelope efflux is achieved. There is a significant gap in knowledge about functions of MFPs in the context of Gram-positive cell envelopes.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.


Identification of a linear filter in cascade with a spiking neuron has been previously considered  under thHere we propose a new system identification methodology to identify a more general NARMAX representation of the nonlinear receptive field in cascade with an ideal-IAF neuron, based only on measurements of the input stimulus and the spike time sequence of the IAF neuron. By using an orthogonal forward selection algorithm we are able to derive the NARMAX representation of a scaled version of the nonlinear filter directly from the reconstructed input of an ideal IAF neuron. The method is further extended to leaky-IAF neurons which require estimating an additional spiking neuron parameter. We use the NARMAX methodology to identify recursively the nonlinear filter and the spiking neuron parameter in the presence of noise. Statistical and dynamical model validation tests are used to check if the identified nonlinear filter models are an adequate representation of the underlying nonlinear information processing mechanisms. The performance and robustness to noise of the proposed methods is demonstrated through numerical simulation studies. Specifically, we compared the generalized (higher-order) frequency response functions (GFRFs) of the original and the identified nonlinear filter  and evaluated, for different noise levels, the SNR of the model predicted output on a validation data set .


This data article contains eleven tables supporting the research article entitled: Cost-Optimal Design For Nearly Zero Energy Office Buildings Located In Warm Climates The data explain the procedure of minimum energy performance requirements presented by the European Directive (EPBD) This files include the application of comparative methodological framework and give the cost-optimal solutions for non-residential building located in Southern Italy. The data describe office sector in which direct the current European policies and investments In particular, the localization of the building, geometrical features, thermal properties of the envelope and technical systems for HVAC are reported in the first sections. Energy efficiency measures related to orientation, walls, windows, heating, cooling, dhw and RES are given in the second part of the group; this data article provides 256 combinations for a financial and macroeconomic analysis. Specifications TableValue of the data•Identification of 256 combinations of energy efficiency measures for office buildings.•Assessment of optimal energy solutions in terms of primary energy consumptions and global costs for non-residential buildings.•Methodological approach to understand and exploit the possible solutions for nZEBs in warm climate.12 gas emissions, global costs) of non-residential buildings located in warm climate .Eleven tables are provided in order to give the input  and output data  having 1153 degree-days. The country is characterized of a non-extreme winter, but high aridity in summer and rainfall concentered in autumn and winter The input data about the geometrical features  are derived from ENEA reports The aim of the research is to reduce the energy demands and the primary energy consumptions for office buildings in order to reach nZEBs level by applying several combinations of variants. The measures proposed include different type of walls, windows and technical systems . The selected highly external precast walls and the type of windows frame are reported in the 2 gas emissions, primary energy consumptions, global costs and the performance classification are listed in terms of financial analysis. Macroeconomic output values are given only for the best range of solutions (The software ProCasaClima2015 has been used for the evaluation of the energy demands, the primary energy consumptions and the global costs for all combinations, according with olutions .2 gas emissions ranges. Each one is characterized by a combination of specific technical system variants.The analysis led to define seven ranges of primary energy consumptions. 2 gas emissions, primary energy consumptions and costs have been obtained for several solutions compared to the reference building.The study contributes to define the strategies to reach high performance energy buildings for Mediterranean climate according with the national requirements. The reduction of COAll authors participated in preparing the research from the beginning to ends, such as establishing research design, method and analysis. All authors discussed and finalized the analysis results to prepare manuscript according to the progress of research.


P < 0.0000). The study showed an increase in the muscle fatigue of the temporal and masseter muscles correlated with the intensity of temporomandibular dysfunction symptoms in patients. The use of surface electromyography in assessing muscle fatigue is an excellent diagnostic tool for identifying patients with temporomandibular dysfunction.The aim of this study is to evaluate muscle fatigue in the temporal and masseter muscles in patients with temporomandibular dysfunction (TMD). Two hundred volunteers aged 19.3 to 27.8 years  participated in this study. Electromyographical (EMG) recordings were performed using a DAB-Bluetooth Instrument . Muscle fatigue was evaluated on the basis of a maximum effort test. The test was performed during a 10-second maximum isometric contraction (MVC) of the jaws. An analysis of changes in the mean power frequency of the two pairs of temporal and masseter muscles (MPF%) revealed significant differences in the groups of patients with varying degrees of temporomandibular disorders according to Di ( According to various reports, the prevalence of functional disorders in the population aged 3–74 years ranges from 7% to 84% –6. AccorA review of epidemiological studies conducted by McNeill  indicateSimilar conclusions regarding the disparity between the prevalence of subjective symptoms and the recorded evidence of functional disorders were presented by Mohlin et al.  followinIn the light of the evidence presented, expanding the repertoire of modern noninvasive diagnostic methods should result in obtaining more objective research results –14.The aim of this study is to evaluate muscle fatigue in the temporal and masseter muscles in patients with temporomandibular dysfunction.The research was approved by the Ethics Committee of the Pomeranian Medical University in Szczecin, Poland (number BN-001/45/07) as being consistent with the principles of Good Clinical Practice (GCP). All the patients were informed about the aim and research design and they gave their consent in order to participate.Two hundred volunteers  aged 19.3 to 27.8  referred to the Orthodontic Department of the Pomeranian Medical University in Szczecin participated in this study. Inclusion criteria were that the participants should be aged between 19 and 28 years and express consent to participate voluntarily in the study. As a result of the application of the adopted exclusion criteria listed in Anamnestic interviews which included the patients' general medical history as well as detailed information about their masticatory motor system were conducted. The patients were divided according to a three-point anamnestic index of temporomandibular dysfunction (Ai).The assessment of the function of the masticatory motor system included clinical as well as electromyographic examinations. The former involved visual and auscultatory assessment as well as palpation and made it possible to qualitatively and quantitatively evaluate the function of the masticatory system. The clinical index of temporomandibular dysfunction was used for the analysis of the data obtained from the clinical study . The intEMG recordings were performed using a DAB-Bluetooth Instrument . During these recordings each patient was sitting on a comfortable chair without head support and was instructed to assume a natural head position during electromyographic examination.Surface EMG signals were detected by four silver/silver chloride (Ag/AgCl), disposable, self-adhesive, bipolar electrodes  with a fixed interelectrode distance of 20 mm. The electrodes were positioned on the anterior temporal muscles and the superficial masseter on both the left and the right sides parallel to the muscular fibres, for the anterior temporal muscle: vertically along the anterior margin of the muscle; for the masseter muscle: parallel to the muscular fibres with the upper pole of the electrode at the intersection between the tragus-commissura labiorum and exocanthion-gonion lines. A reference electrode was placed inferior and posterior to the right ear .Before the recordings, in order to reduce impedance, the skin was carefully cleaned with 70% ethyl alcohol and dried. The EMG procedures were performed 5 minutes later.The DAB-Bluetooth Instrument was interfaced with a computer which presented the data graphically and recorded it for further analysis. The EMG signals were amplified, digitized, and digitally filtered.Muscle fatigue was evaluated on the basis of a maximum effort test. The test was performed during a 10-second maximum isometric contraction (MVC) of the jaws. Analysis of the mean power frequency (MPF%), as a variable independent of the complex impedance of the measurement system, did not require the use of a normalization process.The asymmetry between the activity of the left and the right jaw muscles was quantified by the Asymmetry Index (As). It ranges from 0%  to 100%  –20:(1)AsU test were used to verify the hypotheses relating to the existence or absence of differences between the mean values of the independent variables. The statistical significance for verifying all the hypotheses was set at P = 0.05.The Kruskal-Wallis test, the median, and the Mann-Whitney P < 0.0000, The analysis of changes in the mean power frequency of the two pairs of temporal and masseter muscles (MPF%) showed significant differences in the groups with varying severities of temporomandibular dysfunction according to the Di index (P < 0.0000). There was always greater depletion of the interference signal in the case of the masseter muscles relative to the temporal muscles.Resistance to muscle fatigue was modified at the level of the type of muscles examined (P < 0.0004), moderate dysfunction , and severe dysfunction  according to the Di index. There were no significant differences in the fatigue of the right and left temporal muscles in each group of temporomandibular dysfunction according to the Di index (P < 0.0784).Changes in the mean power frequency (MPF%) of temporal muscles during 10 s of maximum voluntary contraction were the lowest in the group with no symptoms of temporomandibular dysfunction (−2.92%). Significantly higher depletion of the interference signal was observed in the group with mild dysfunction , moderate dysfunction , and severe dysfunction  according to the Di index. As in the case of the temporal muscles, the impact of dysfunction on the differences in fatigue between the right and left masseter muscles has not been confirmed (P < 0.0937).Similar to the temporal muscles, changes in the mean power frequency of masseter muscles were the lowest in the group with no symptoms of dysfunction (−3.97%). Significantly higher muscle fatigue, as evidenced by a greater reduction in the mean power frequency, was found in groups with mild dysfunction ) because of the noninvasive nature of measurements that it provides [Electromyography (EMG) is one of the few diagnostic tools that enable direct and objective assessments of muscle function. Practitioners dealing with functional disorders of the masticatory motor system are particularly interested in global electromyography  and its changes linked to function are a reliable and objective indicator of muscle resistance to fatigue. Thus, changes in the frequency of the electrical activity of muscles, being a component of interference signal depletion, are a major predictor of susceptibility to muscle fatigue in EMG recordings. Muscle fatigue can also be determined by an increase in the EMG activity of muscles involved in generating a constant force. This is consistent with the view that generating a constant force as muscle fatigue increases must be associated with an increase in the electrical activity of muscles .Our own examinations showed significant differences with regard to the type of muscles examined. There was a significantly greater depletion of the interference signal in respect of the changes in mean power frequency of the masseter muscles than the temporal muscles during 10 s of maximum isometric contraction in the intercuspal position.Changes in the interference signal with respect to the mean power frequency of muscles during maximum isometric contraction were also a strong predictor of functional disorders in the masticatory motor system. Resistance to fatigue in the temporal and masseter muscles was significantly higher in the group with no symptoms of temporomandibular dysfunction than in the group of patients with symptoms of dysfunction according to the Di index. There was a significantly greater depletion of the interference signal for masseter and temporal muscles in the group with TMD.Measurements of the mean power frequency of temporal and masseter muscles also showed high discriminatory efficiency for subjects with varying severities of temporomandibular dysfunctions according to the Di index. There were significant differences in terms of fatigue between the groups with varying severities of dysfunction for both temporal and masseter muscles.The results of the study were based on the clinical index of temporomandibular dysfunction (Di). This index is simple and easy to use and is extensively used in research . AlthougIn studies of masticatory muscle fatigue conducted by Sforza et al.  a muscleHori et al.  recordedIn studies conducted by Gay et al.  surface A study by Castroflorio et al.  concerneLiu et al.  found siThe studies presented, whose observations are consistent with the results of our own findings, provide justification for using the analysis of muscle fatigue in the identification and discrimination of subjects with symptoms of masticatory system dysfunction.The results of the presented study showed an increase in the fatigue of temporal and masseter muscles in direct proportion to the severity of symptoms of temporomandibular dysfunction in the examined patients.The use of surface electromyography in the assessment of muscle fatigue is an excellent diagnostic tool for identifying patients with temporomandibular dysfunction.


The dendrite of the cerebellar Purkinje cell is one of the most complex structures in the mammalian brain, receiving more than 150,000 synaptic inputs. It is also one of the most extensively modelled neurons in the mammalian brain, with theoretical analysis of the input-output relationships in its dendrite extending back 40 years. While most of this experimental and modelling work has been conducted using mammalian neurons, it has also often been noted that overall cerebellar structure as well as the general morphology of Purkinje cells has been highly conserved in all vertebrate species. The work described here seeks to identify conserved features of Purkinje cell function by examining the relationship between structure and function in a range of vertebrate species from fish to mammals.This study is based on passive compartmental models constructed from anatomical reconstructions of Purkinje cells obtained from fish, reptiles, birds and mammals. Morphologically, while the Purkinje cells of each of the species are flattened structures and appear to have the same geometrical relationship to other elements of the cerebellar cortical circuitry, the dendrites of birds, alligators and mammals have a much more highly articulated dendritic branching structure than the dendrites of fish and turtles. In previous studies of the passive electrical properties of these dendrites , we have


The rarity of glucagonoma imposes a challenge with most patients being diagnosed after a long period of treatment for their skin rash (months-years). Awareness of physicians and dermatologists of the characteristic necrolytic migratory erythema often leads to early diagnosis. Early diagnosis of glucagonoma even in the presence of resectable liver metastases may allow curative resection. Herein, we present a typical case of glucagonoma treated at our center and review the literature pertinent to its management.  Since its first description by Becker in 1942 This highlights the importance of early diagnosis since complete resection of the primary tumor and limiting metastases offers the only chance of cure. The slow growth of the tumor coupled with advances in liver surgery and transplantation may allow curative resection in patients with metastatic disease confined to the liver.Novel advances in management of metastatic pancreatic neuroendocrine tumors include complex liver resections and liver transplantation , percuta


The aim of this article was to suggest some changes in the teaching-learning process methodology of the judo osoto-guruma technique, establishing the action sequences and the most frequent technical errors committed when performing them. The study was carried out with the participation of 45 students with no experience regarding the fundamentals of judo  from the Bachelor of Science of Physical Activity and Sport Science at the University of Vigo. The proceeding consisted of a systematic observation of a video recording registered during the technique execution. Data obtained were analyzed by means of descriptive statistics and sequential analysis of T-Patterns (obtained with THEME v.5. Software), identifying: a) the presence of typical inaccuracies during the technique performance; b) a number of chained errors affecting body balance, the position of the supporting foot, the blocking action and the final action of the arms. Findings allowed to suggest some motor tasks to correct the identified inaccuracies, the proper sequential actions to make the execution more effective and some recommendations for the use of feedback. Moreover, these findings could be useful for other professionals in order to correct the key technical errors and prevent diverse injuries. Judo is one of the most important martial art sports practiced in the world . It inclIn this respect, the requirements for the improvement of the technical and tactical preparation have been the focus of some studies which achieved meaningful results with theoretical and practical applications for judo coaching . As an eLack of comprehension of the relation between a poor technique performance and the circumstances that may cause different forms of injuries  has also recently raised a debate . In thisMany injuries are attributed to repetitive actions performed with a poor technique. These actions can bring about an excessive pressure on particular joints or muscles contributing to an injury.Finally, the feedback given by the trainees  and the Therefore, the present research is intended to assist coaches and teachers of judo, showing the behavior patterns (errors and their sequences) hidden from visual perception. With the aim of achieving the technical understanding necessary to improve the teaching-learning process, we performed a systematic observational study. In this particular case, the most relevant errors and sequences of errors of the osotoguruma judo technique have been studied. The findings allow to propose some methodological recommendations in the development of tasks. The feedback of the process can be useful for performing the osoto-guruma throw efficiently and for helping professionals to correct the key technical errors, avoiding diverse injuries.In this research, we used an observational methodology  which prThe observational design  was nomoNovice students  were filmed while following a subject of judo at the Faculty of Sciences of Education and Sport at the University of Vigo. The recordings were made during the course of five academic years (2003 to 2008), with the written authorization of the participants that the videos could be used for research purposes. All the ethical standards throughout the study were in accordance with the American Psychological Association (APA).The observational instrument developed for this study was the SOBJUDO-OSGU , combiniThe SOBJUDO-OSGU instrument fits the observational design presented. Thus, it is multidimensional in nature including the following structural criteria: grip, off-balance, right-foot position, right-arm position, hip position, left-foot position, leg′s action, blocking action, throw stage, control stage and globality. Each dimension gives rise to a system of categories that meets the conditions of exhaustiveness and mutual exclusivity (EME).The data collection was performed by recording the student from two different angles with two digital cameras (JVC GZ-MG21E). To assist the analysis of the projections recorded, the filmed material was edited with the software Pinnacle Studio v.12. The software Match Vision Studio Premium v.3.0. , a multiThe technical execution of osoto-guruma was filmed all along the ordinary training period (∼4 months with 3 hrs of practice per week) at the University of Vigo, involving the learning process of a total of 17 projections. We only used the data collected from 10 of the techniques. The selection criteria of the techniques studied were based on: 1) the premises of an investigation reporting the performance difficulty of certain techniques of Gokyo ; and 2) The quality control of the data recorded by two observers was performed by means of the Cohen’s Kappa  coefficient (k), that guarantees the agreement between them when the value k is >0.80. The software GSEQ  providedThe excel files obtained allowed to have the frequencies of all the codes of occurrences registered, which were successively transformed in order to enable further analyses. The codes of the instrument of observation SOBJUDO-OSGU were entered into the software THEME , 2005, aThe frequency of occurrence of the different errors committed during the osotoguruma throw performance was determined by means of a descriptive analysis using SPSS 15. The results of this analysis are shown in In The most common errors are those related to the initial imbalance (NOB), the improper position of the supporting foot (IPSF) and the incorrect blocking action (SF), with a deficient traction action and an incorrect direction of the arms accompanied by an insufficient rotation of the trunk at the end of the technique (IAT).In osoto-guruma technique. Thus, in tori to replace the leg previously used to perform the sweeping (REAP-RBL) .After a thorough revision of the literature, we have confirmed the lack of scientific studies regarding the technical errors and its sequences in judo. Only the most relevant authors of this field of study have pointed out the key aspects or the most common technical errors when describing a technique . Such inThus, several authors have highlighted that the imbalance of the opponent at the beginning of the technical action must be directed towards the back right diagonal (NOB) and tori must make uke be balanced only by the heel of his right foot .The incorrect placement of tori’s supporting foot in the second and third phases of the projection (IPSF) is one of the typical errors observed, what has also been mentioned by other authors . AccordiAnother common error detected is the incorrect distribution of tori’s mass on legs at the time of throwing the opponent. The most correct approach would be to lean the body mass on the leg that does not participate in the blocking action (SF and WLB). However, there is a tendency to poise the right foot fully on the floor. Although nobody has specifically mentioned this aspect as a typical error or a fundamental point, some authors state that the body mass should entirely fall on the left leg .Additionally, some individuals perform a sweeping action instead of performing the blocking action (REAP). Some authors, such as Several authors, such as The sequential pattern analysis of errors reveals that an improper imbalance of uke leads to inaccurate positioning of the body, preventing tori from distributing body mass in a suitable way to perform the projection. That makes it difficult to carry out an optimal action with the arms and to perform the body rotation towards the right direction. Few references were found regarding the pattern of this chain of errors and, to our knowledge, the connection between the major errors observed in osoto-guruma judo-technique had not previously been explained in detail.Several authors have reported some dual relationships between errors. One of the limitations of this study was the time available for students to practice (four months), as well as the nature of the participants (university students). Therefore, future research employing longer learning periods (>10 months), other origins of the participants  or different age groups could be interesting. The process of learning judo techniques could possibly be better analyzed this way, establishing guidelines and setting the practice time required to identify the most common mistakes. Further studies could also be undertaken in order to identify the factors influencing the number and importance of errors and their sequential registration.A proper unbalance of the opponent’s body promotes the correct location of the supporting foot.A proper placement of the supporting foot and a suitable distribution of the body mass simplify the subsequent blocking action on the uke’s body and the correct execution of the projection phase of osoto-guruma technique.It is a matter of fact that the teaching and learning process of osoto-guruma technique could be improved by paying special attention to the following statements regarding the movement sequences, which will ensure that the throw is correctly executed:The results of this study also enable us to suggest a number of strategies, based on the knowledge of performance, with the aim of improving the teaching and learning of the osotoguruma technique.When demonstrating the technique, the student should pay attention to the key points highlighted in this study. As far as the throw theoretical aspects are concerned, we think that coaches could find it useful to incorporate some video-recordings or other images illustrating the fundamental features and the common errors detected here. In any case, teachers or coaches should only focus on the most relevant aspects.Instructors could design tasks or drills that draw the student’s attention to the most significant errors and sequences of behavior detected.After a throw execution in the training, the subsequent communication between coaches and students could be improved by providing a more precise feedback. Coaches should firstly consider the most significant errors and sequences identified in the present study, leaving others for a later stage of the training. It would also be helpful to take into consideration just a few key aspects to avoid overloading the students with an excess of information. The results of this study can provide a platform for different kinds of feedback , which should always be positive in nature.Coaches could elaborate some observation/evaluation sheets based on the category system of the observation instrument used in this study. One model should be intended for the students to work in groups of three, with one of the trainees observing the other two while they are performing the throw. Thus, this student would conduct an observational analysis using the evaluation sheet, noting the errors made and providing an immediate feedback. The same observational analysis could also be carried out later by means of video recordings.


Growing clinical evidences indicate the benefits of human milk (HM) for appropriate growth and development of a newborns: the particular composition make it a unique and inimitable nutrient . Mother'Nonetheless storage and processing of human milk may reduce some biological components, which may diminish its health benefits but when donor milk is used instead of formula, it is demonstrated a reduction in the incidence of necrotizing enterocolitis and an enhanced feeding tolerance . PasteurFuture research should focus on the improvement of milk processing in HMB, particularly of heat treatment on the optimization of DM fortification and on further evaluation of the potential clinical benefits of processed and fortified DM.


Frontiers in Plant Science research topic provides a snapshot of current research into the application of environmental phytoremediation strategies.Human industry, farming, and waste disposal practices have resulted in the large-scale contamination of soil and water with organic compounds and heavy metals, with detrimental effects on ecosystems and human health. Conventional soil remediation methods are expensive and often involve the storage of soil in designated areas, postponing rather than solving the problem. In the last decade, the pressing need to find alternative methods has highlighted the scientific and economic benefits of plants and their associated microorganisms, which can be used for the reclamation of polluted soil and water Meagher, . This isPteris vittata with or without bacterial strains selected from autochthonous rhizosphere-derived microorganisms [chosen for their resistance to high concentrations of arsenic (As) and their ability to reduce arsenate to arsenite] showed that the efficiency of phytoextraction increased when P. vittata plants were inoculated with the selected microbial communities  and Astragalus bisulcatus (Fabaceae), and the related non-accumulators Physaria bellis (Brassicaceae) and Medicago sativa (Fabaceae), revealed that isolates from Se hyperaccumulator species were more resistant to selenate and selenite, could reduce selenite to elemental Se, could reduce nitrite and produce siderophores, and several strains also showed the ability to promote plant growth  with three of these isolates promoted plant growth and the removal of toxic metals from polluted soil, demonstrating that the interaction between plants and bacterial strains identified in contaminated areas could improve plant growth and the efficiency of phytoremediation (Khan et al., Brassica juncea and Ricinus communis plants inoculated with rhizospheric and endophytic bacteria isolated from a polluted serpentine environment accumulated more biomass and heavy metals than non-inoculated control plants (Ma et al., The phytoremediation potential of plants inoculated with bacteria isolated from the rhizosphere and endosphere of other plants grown in soil contaminated with heavy metals is discussed in two articles (Khan et al., The beneficial interaction between plants and rhizobia for the remediation of contaminated soil is discussed by Teng et al. . CertainPhragmites australis plants were exposed to carbamazepine, a widely-used drug that is present in the environment as a persistent and recalcitrant contaminant (Ternes et al., Two further articles discuss the use of plants and their associated microorganisms for the reclamation of land polluted with organic contaminants (Germaine et al., It is notable that all the articles submitted in this research topic focused on the use of naturally-occurring hyperaccumulator species rather than transgenic plants and/or microorganisms, although genetically-engineered plants and microbes can also be used for the efficient treatment of polluted soil and water (Van Aben, 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.


Hereditary cerebellar ataxias are a wide group of progressive, degenerative diseases, which manifest as lack of control and coordination of voluntary movements due to progressive loss of Purkinje cells and other cell types in the cerebellum. Cerebellar degeneration could affect people of any age, is often diagnosed after symptoms start to manifest and no prevention and no causal and really effective therapy is available today.There is high variability in pathogenesis in human cerebellar degenerations and high variability in onset and progress of the disease. Though the basal manifestation of all cerebellar degenerations is similar as it is related to dysfunction of the cerebellum, there are some differences between individual types of them and also some variability in the frame of one disease making the clinical diagnosis difficult. The manifestation of the mutation could be also modified by the genetic background. For all of that, individual approach of treatment is necessary.There is a vide spectrum of mouse models of genetically determined cerebellar degenerations including both spontaneous mutants and transgenic mice, some of which are available in several mouse strains. This situation is analogous to variability of human hereditary cerebellar disorders and genetic heterogeneity of human population. Mouse models can be used for investigation of efficiency of experimental therapy in individual types of cerebellar degenerations and for studying of the effect of genetic background on the pathological process. Such research could allow identifying factors determining progress of the disease and influencing the effect of the therapy. This is necessary to choose the optimal treatment for each individual patient and for development of new therapeutic methods.One of therapies which could benefit from such research is stem cell and neurotransplantation therapy. So far it seems promising in slowing down progress, but it might even mitigate neurological deficit caused by the cerebellar degeneration.Nevertheless, as experiments in mice shoved different types of grafts have different effects. For example mesenchymal stem cells prevent neurodegeneration progression, but do not reverse already developed cell loss and neurological deficit. Transplanted suspension of embryonic cerebellar cells generates new graft-derived Purkinje cells in Purkinje cell degeneration mice and improvement of motor function was described in them. On the other hand, in Lurcher mice functional benefit of cerebellar tissue transplantation has not been achieved yet. In addition, cultivated embryonic neural stem cells survive well in the host cerebellum and despite they do not create any new Purkinje cells they have been shown to rescue Purkinje cells in a mouse model of Niemann-Pick disease.Genetically defined mouse strains with different mutations causing neurodegenerative diseases and different mouse strain backgrounds for the same mutations and analysis of their genome and proteome would be valuable tool to identify genetic markers and factors important for assessment of prognosis and management of appropriate stem-cell therapy and for development of new therapeutic approaches based on the principles of personalized medicine.


The authors wish to retract this article at the request of the Scottish Haemophilus Legionella Meningococcus Pneumococcus Reference Laboratory (SHLMPRL). Although the work was part of an independently-funded research grant awarded to Stuart Clarke, Matthew Diggle and Robert Davies by the Scottish Executive, they did not have permission from the current SHLMPRL management to publish the data in their current form. The anonymised data in the MLST database will remain available. The authors apologise to the readers.


In 1980, Clair C. Patterson stated: “Sometime in the near future it probably will be shown that the older urban areas of the United States have been rendered more or less uninhabitable by the millions of tons of poisonous industrial lead residues that have accumulated in cities during the past century”. We live in the near future about which this quote expressed concern. This special volume of 19 papers explores the status of scientific evidence regarding Dr. Patterson’s statement on the habitability of the environments of communities. Authors from 10 countries describe a variety of lead issues in the context of large and small communities, smelter sites, lead industries, lead-based painted houses, and vehicle fuel treated with lead additives dispersed by traffic. These articles represent the microcosm of the larger health issues associated with lead. The challenges of lead risk require a concerted global action for primary prevention. Geochemist Clair C. Patterson became distressed about the health impacts of the massiveness of the 20th century quantities of lead in commerce and their residues . This toThe theme of lead risk assessment and health effects was explored and interpreted by the authors of 19 manuscripts. The papers reflect the international scope of lead research conducted in Australia ,3, BeninThe critical issue at this point is the need to revitalize primary prevention and develop skills and tools to curtail the risks of lead exposure. The most vulnerable individuals to the risks of lead exposure are children and because the exposure appears without symptoms this makes the issue invisible. One tendency is to rely on children’s blood lead levels as a tool for discovery of environmental lead. This is not primary prevention. Unexpected results continue to mount regarding the long-term health outcomes associated with ever smaller amounts of lead exposure during early stages of development .lead loading. Within interior environments the practice of measuring the lead content of the vacuum cleaner bag dust was discarded in favor of floor wiping methods that measure lead loading. The methodology change occurred because there was a stronger association between lead loading and blood lead than between lead content and blood lead. In the outside soil environment, lead content is the standard method of measurement. However, an improved understanding about the quantity of lead in the environment could be achieved by recognizing the amount of lead loading of the soil surface; lead loading of soil generally exceeds by large factors the current standard for interior floor surfaces (which some consider too high) [Along with policy matters there are scientific barriers that thwart primary prevention progress. Measurement techniques are critical for addressing environmental lead and human exposure, and instrumentation developments, such as hand-held field X-ray Fluorescence, have allowed major strides toward identifying sources of lead in the environment. However, in the case of soil there is a critical issue apropos the difference between lead content and oo high) .margin-of-safety. The engineering and toxicology/pharmacology professions recognize the need to apply margin-of-safety factors to protect human health within the context of their respective trades. The margin-of-safety concept has not been included in the standards for lead and the outcome has been a continuing series of failures to protect children [margin-of-safety factor is an essential addition to the standards to make them relevant for protecting children [Another scientific issue involves the concept of children . Given tchildren . Primary


Deep brain stimulation (DBS) is an established therapy for movement disorders, including tremor, dystonia, and Parkinson's disease, but the mechanisms of action are not well understood. Symptom suppression by DBS typically requires stimulation frequencies ≥100 Hz, but when the frequency is increased above ~2 kHz, the effectiveness in tremor suppression declines (Benabid et al.,  Deep brain stimulation (DBS) is an effective treatment for the motor symptoms of movement disorders including essential tremor, Parkinson's disease, and dystonia, and recent data suggest that it may also be effective to treat epilepsy, obsessive-compulsive disorder, and depression. Although the mechanisms of action of DBS remain unclear, its effects are strongly dependent on stimulation frequency  implemented in NEURON v7.2   as a measure of the regularity of neuronal firing  and κ, the number of discrete bins per ISI decade, was set to 20  pairs  approximated those of a deterministic model, albeit with a higher overall entropy. Conversely, the responses of the stochastic model with a low density of sodium channels (200 channels per node) were substantially more variable than those of the deterministic model, and, unlike the other two models, this low density stochastic model nerve fiber exhibited spontaneous firing.The evoked patterns of activity in each model variant were quantified by calculating the firing pattern entropy for each axon in the population with the extracellular stimulation intensity selected to evoke action potential firing in half of the model axons at a stimulation frequency of 100 Hz Figure . At freqHigher stimulation frequencies produced block of conduction in fibers close to the electrode and the resulting cessation of activity produced firing pattern entropy of zero , the patterns and changes in entropy were similar to those in the deterministic model, and to reduce computational cost and complexity we used the deterministic model to analyze the effects of DBS on intrinsically active (bursting) model nerve fibers.We used a population of 100 deterministic model nerve fibers, with intrinsic burst activity generated by intracellular current injection at one end of each fiber, to quantify the effect of extracellular stimulation on firing patterns. The ability to mask the intrinsic bursting in the model depends on the distance between the node closest to the electrode and the proximal end of the axon where the patterned intracellular stimuli were delivered .We quantified the effect of increasing stimulation amplitude on the entropy of the firing patterns of intrinsically bursting model nerve fibers at different electrode to fiber distances Figure . At 200 The firing patterns of the fiber populations are summarized in the histograms of inter-spike interval pairs  generate conduction block of activity in the model nerve fibers or (2) generate highly irregular patterns of activity in the model nerve fibers. Conduction block with kHz frequency signals has been demonstrated experimentally (Bowman and McNeal, DBS at clinically-effective frequencies entrains spike activity both downstream and upstream from the site of stimulation, although the entrainment occurs only for a fraction of the stimulation pulses (Agnesi et al., This modeling study enabled the identification of possible causes of the increase in stimulation amplitude required to suppress tremor with kHz frequency DBS. However, the model included a limited representation of possible geometries; the fibers were all orientated parallel to each other and had a linear geometry, which is not representative of the true anatomical arrangement of axons around the electrode. Furthermore, the model did not include other neuronal elements that are also affected by extracellular stimulation and may contribute to effects of thalamic DBS on tremor. Accumulation of potassium within the peri-axonal space may contribute to functional block of axons in response to high-frequency stimulation (Bellinger et al., Increased irregularity in the pattern of neural firing has been suggested as the cause of symptom exacerbation by low frequency DBS while masking of intrinsic neural activity and the consequent regularization of neuronal firing by high frequency DBS has been hypothesized as responsible for the therapeutic success of DBS (Grill et al., The loss of tremor suppression by thalamic DBS at kHz frequencies can be explained by the increases in the entropy of neuronal firing generated by kHz frequency DBS in model neurons. Entropy was subsequently reduced when the amplitude of the stimulus was further increased, consistent with the experimental observations of increased stimulation amplitude thresholds for tremor reduction with kHz frequency DBS (Benabid et al., JC performed computer simulations and analyzed the data. JC and WG designed the research and wrote the paper.This work was supported by NIH R01 NS040894 and R37 NS040894.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 authors re-exported source data from the animal ventilator (FlexiVent) and compared the output with the raw data originally received from the animal pulmonary physiology laboratory. The results from these initial comparisons suggested potential inconsistencies in the data, so the authors requested that an independent laboratory replicate the experiments of animal airway physiology presented in Figure 1 and Figure 4. The results of the replicated experiments validated the originally reported central role of mindin in airway hyper-responsiveness after exposure to either lipopolysaccharide (LPS) or ozone.Because the animal physiology laboratory at Duke University also analyzed cytokines, the authors had an independent laboratory replicate experiments to analyze the original role of cytokines reported in Figure 3 and Figure 6. In these replicate studies, which were limited in the number of animals and samples tested, the authors did not observe the same results and could not definitively determine whether or not the findings were valid.The inconsistent results led the authors to take a conservative approach, and they agreed to retract this paper. They regret any inconvenience to the scientific community.


Histopathological examination of the tissue samples removed from 50 tumor-like growths  revealed three types of tumors; squamous cell carcinoma (70%), spiny keratoderma (22%) and fibroma (8%). An increased incidence of tumors was recorded in the medial when compared to the lateral toenails in both sexes. In females, the incidence in the medial toenails was 90/259 (34.75%) and 71/259 (27.41%) in the right and left forelimbs respectively when compared to the lateral toenails which was 25/259 (9.65%) and 5/259 (1.93%) for the respective right and left forelimbs. In the hind limbs, this ratio was 29/259 (11.20%) and 20/259 (7.72%) for right and left medial toenails respectively, whereas it was 17/259 (6.56%) and 2/259 (0.77%) for the right and left lateral toenails respectively. Similar to the observations in female camels, male camels also showed a higher incidence of these tumors in the medial when compared to the lateral toenails in both fore and hind limbs. Based on these findings, we conclude that in the dromedary camels, the medial toenails of the fore limbs are most commonly affected with tumors; with the most common tumor being the squamous cell carcinoma.A total of 275 dromedary camels  of local  Camelids are modified digitigrades with a small, non-weight bearing nail which is similar to a human nail and is located at the extremity of each digit. The nail is closely attached to the third phalanx via the corium. The pectoral limb is the weight bearing axis of the body and there is a slight difference in the anatomical configuration between the lateral and medial metacarpal bones and the digits in camels.The proximal articular surface of the third metacarpal bone is slightly higher than that of the fourth metacarpal and its mediopalmar facet articulates only with the second carpal bone.The distal articular surface of the third metacarpal bone is also at a slightly higher plane than that of the fourth metacarpal bone. The first and second lateral phalanges are ~2-3 mm longer than their medial counter parts .This anatomical configuration results in a slight but noticeable lateral deviation of the forelimbs extending from the knee to the foot. This configuration may subject the medial digit to increased pressure when compared to the lateral digit, rendering the former more prone and vulnerable to pressure-related injuries leading to abnormal growth lesions .et al., 1997), squamous cell carcinoma of the foot and chondrosarcoma of the left carpal joint in camels .Although the hind limbs in the camel are not a part of the weight bearing axis of the body, the anatomical configuration of the metatarsal bones and the digits resembles that of the corresponding bones of the fore limbs, as the first and second lateral phalanges are 1-2 mm longer than their medial counter parts . Previous reports on tumors in camelids include squamous cell carcinoma of the skin in a llama , cutaneous melanocytoma in a llama  and a basal cell carcinoma in a dromedary camel  have been previously published.A general report of neoplasia in camels .The development of the tumor is progressive and the animal is often presented for treatment when the tumor is at an advanced stage. Onychia (inflammation of the corium beneath the nail) and paronychia (inflammation of the tissue at the margins of the nail) in camelids can result from either contusions or lacerations of the nail. Neglected toenail trimming in such cases may allow the infection to migrate dorsally under the nail .If further neglected, such conditions can exacerbate and act aggressively leading to the involvement of the soft tissue beyond the toenail.A squamous cell carcinoma typically originates from the skin around the toenail and commonly affects the surrounding bone and soft tissue. Because this tumor spreads slowly, it can often be visualized before it spreads to other areas of the body.The most common symptom at this stage is a swollen toe with or without lameness. Radical surgical excision of the mass along with the toenail is most likely the only treatment that can consistently provide relief to the animal and also potentially avoid metastasis of the tumor to other sites .Squamous cell carcinoma is also reported in the dogs. Similar to that observed in the camel, the tumor in the dogs affects only one toe and is noticeable grossly as solid, raised skin mass over the affected toe. However, over time the tumor expands and loses its original solid mass-like appearance as the tissue within the mass dies. Eventually the tumor ulcerates and subsequently extends proximally to involve the digit .In our experience, the toenail tumor in the camel follows almost a similar course as that reported in the dog.Because the toenail/digit tumors in the dromedary camel are very frequent in the emirate of Abu Dhabi, United Arab Emirates, we sought to study this widespread condition in depth including an investigation of the incidence and nature of this endemic disease.The study included 275 cases  that displayed growth around the soft tissues above the nail. These cases were reported to the Central Veterinary Hospital, Al-Wathba, Abu Dhabi, United Arab Emirates during a period of 8 years . The cases were categorized on the basis of sex, the limb and toenail involved .Our study shows that the growth involved the toenail only  or almosIn each case, the severity and extent of involvement of the digit was carefully evaluated in order to decide the most appropriate surgical procedure to provide relief to the suffering animal.When only the toenail was involved, the third phalanx along with the toenail was removed by disarticulation at the distal interphalangeal joint . In caseWhen the tumor involved more than half or the entire digit; unilateral disarticulation of the digit was performed at the metacarpo-phalangeal or metatarso-phalangeal joint with excision of the diseased tissue while preserving the normal sole .This procedure resulted in restoring the maximum weight bearing surface of the foot, thus enabling the animal to attain a near-normal gait soon after the recovery.In all surgical interventions, a strict adherence to the goals of cancer surgery was assured: viz; a complete excision of the cancerous tissue along with the surrounding healthy tissue to minimize chances of tumor recurrence and to prevent an adverse metastasis.A total of 275 cases were operated for tumor-like lesions. Tissue samples from 50 cases  showing different growth patterns were collected for histological examination. Representative sections from each tumor tissue were fixed in 10% neutral buffered formalin and were submitted to the Pathology Laboratory of Al-Noor Hospital, Abu Dhabi for a detailed histopathological evaluation.P < 0.05.The data was analysed using the chi-square test. The criterion for statistical significance was set at None of the operative wounds healed through first intention. The wounds in different animals required variable time periods to heal ranging from 2 to 4 months. Recurrence of the tumor was not observed in any of the operated cases.An increased incidence of the tumors was recorded in the medial toenails/digits of the fore and hind limbs in both sexes Tables  and 3. IHistopathological examination revealed that the toenail tumors included one of three following types; Squamous Cell Carcinoma, Spiny Keratoderma or fibroma. The incidence of three different types of toenail tumors (in 50 tissue samples collected) is shown in Squamous Cell Carcinoma lesions consisted of moderate to well-differentiated sheets of small and average sized squamous cells.Frequent clusters of anaplastic squamous epithelial cells with central keratin pearls were also observed. The nuclei were larger in size and had an average number of 2-3 nucleoli per nucleus.The lesions showed frequent angulations with desmoplastic stroma and polymorphic inflammatory infiltrate. No vascular or perineural invasion was observed .Spiny Keratoderma lesions had thick spiny keratotic projections consisting of a well-defined compact column of parakeratotic horn material directly continuous with granular layer. Abrupt transition to orthokeratotic corneal layer at the margins of parakeratotic column was also observed. No dyskeratotic or vacuolated keratinocytes were observed in the underlying epidermis. Furthermore, no malignancy was observed .Fibroma lesions had thick skin tissue showing evident areas of acanthosis and spiny hyperkeratosis. There was abnormal deposition of fibrocollagenous material involving up to the subcutis with wavy fibrous tissue infiltrating and dissecting the underlying structures including the pileosebaceous units, muscles and sweat glands. Whorl appearance was also noticed in some of the areas .et al., 1995).None of the surgical wounds healed through first intention. Considering the anatomic location of the lesions and the type of surgical manipulations required, first intention healing of the wounds in such cases is not likely . Complete surgical excision of the tumor along with the surrounding healthy tissue most likely minimized the probability of tumor recurrence .In our opinion, the possible reason for the lower incidence of tumors in the hind limbs is that these are not a part of weight bearing axis of the body and therefore, are not subjected to higher pressure under the body weight of the animal. However, the anatomical configuration of the metatarsal bones and the digits resembles that of the fore limbs. This may be a plausible reason for an increased incidence of tumors in the medial when compared to the lateral toenails/digits in the hind limbs .et al., 1995; Rogers et al., 1997; Al-Hizab et al., 2007; Janardhan et al., 2011).The significant observation of our study that clinically aggressive tumor lesions have increased chances of being malignant agrees well with the previous reports (Tageldin and Omer, 1986; Gahlot In summary, salient findings from our study reveal that the medial toenails of the fore limbs are frequently prone to squamous cell carcinomas and that a timely surgical excision of the tumorous mass completely alleviates this afflictive condition in camels.


The ion channels kinetics are affected by the trauma-induced damage to neural membrane structure. The density of affected channels is at its highest in the nodes and the axon initial segment (AIS). In this study we focus on the consequences of modifying sodium channels kinetics in the AIS to model the effect of damage. It is inspired by a similar study on damaged nodes of Ranvier  and by eo on AIS ,3. The AA neuron was simulated as three sections, each containing multiple compartments: the soma, the initial segment and the myelinated axon. Each compartment was modeled by the classical Hodgkin-Huxley equations using appropriate densities for each type of ion channel. The types of channels and their distributions were based on a previous study looking specifically at cortical pyramidal neurons having Nav1.2 and Nav1.6 at the AIS . The kinWe explored the effect of damage on the initiation and propagation of APs during repeated stimuli which deplete concentration gradients. Our model allows the investigation of the effect of CLS on the location and duration of the initiation and the threshold duration of Ap-initiatingcurrents. We find that the current threshold for action potential initiation decreases with increased damage or decreased length of the AIS.