Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling.
Oligodendrocytes undergo extensive changes as they differentiate from progenitors into myelinating cells. To better understand the molecular mechanisms underlying this transformation, we performed a comparative analysis using gene expression profiling of A2B5+ oligodendrocyte progenitors and O4+ oligodendrocytes. Cells were sort-purified ex vivo from postnatal rat brain using flow cytometry. Using Affymetrix microarrays, 1707 transcripts were identified with a more than twofold increase in expression in O4+ oligodendrocytes. Many genes required for oligodendrocyte differentiation were upregulated in O4+ oligodendrocytes, including numerous genes encoding myelin proteins. Transcriptional changes included genes required for cell adhesion, actin cytoskeleton regulation, and fatty acid and cholesterol biosynthesis. At the O4+ stage, there was an increase in expression of a novel proline-rich transmembrane protein (Prmp). Localized to the plasma membrane, Prmp displays adhesive properties that may be important for linking the extracellular matrix to the actin cytoskeleton. Together, our results highlight the usefulness of this discovery-driven experimental strategy to identify genes relevant to oligodendrocyte differentiation and myelination.


The association between IUGR and maternal inherited thrombophilias: A case-control study.
One of the risk factors for vascular obstetric complications, such as intrauterine growth restriction (IUGR), is inherited thrombophilias. Nevertheless, routine screening for thrombophilias is not endorsed in pregnant women due to their low prevalence and conflicting results of published studies regarding the usefulness of screening in these patients. The cause of IUGR remains unknown in almost 1 quarter of cases. There are no published studies evaluating the association of inherited thrombophilias and IUGR in patients with IUGR of unknown origin. Understanding and preventing IUGR is an important public health concern, as IUGR has been associated with fetal mortality and neonatal morbidity, as well as adverse long-standing consequences. This study aimed to evaluate the prevalence of inherited thrombophilias in IUGR of unknown cause and to test the association between the inherited thrombophilias and IUGR of unknown cause.This study included 33 cases of IUGR of unknown cause tested for inherited thrombophilias and 66 controls individually matched for age, ethnicity, and smoking status.Patients with plasminogen activator inhibitor 1 (PAI-1) and methylenetetrahydrofolate reductase (MTHFR) had significantly higher odds for IUGR of unknown cause (P < .001 and P = .002, respectively) with OR 13.546 (CI 95% 3.79-48.37) and 8.139 (CI 95% 2.20-30.10), respectively. A positive association between other inherited thrombophilias (homozygous 20210 prothrombin gene mutation and homozygous factor V Leiden) and IUGR of unknown cause was also found, P = .096, OR 6.106 (CI 95% 0.72-51.30), although it was not statistically significant (P = .096, OR = 6.106, CI 95% 0.72-51.30).Our results indicate that PAI-1 and MTHFR thrombophilias represent risk factors for IUGR of otherwise unidentified cause.


Manipulating Gene Expression in the Chick Embryo.
The chick embryo is a well-established representative of amniote embryos, which has been used to make many discoveries, including many major concepts, which have moved our knowledge of developmental biology in hugely important ways. The chick has a relatively compact genome and is easily amenable to embryological manipulations and in vivo imaging. Morpholino gene manipulations have been used in a variety of contexts, and constitute a quick and versatile molecular tool. Here we describe methods to deliver morpholinos to chick embryos, allowing targeting of specific cell populations at defined developmental stages, using two stages as examples: the epiblast of the embryo in the first day of incubation, when the primary germ layers of the embryo are specified, and in ovo electroporation of the neural tube as an example of a later stage. With slight modifications, these general methods can be used to target other embryonic tissues.


[Analysis of expectations on the nurse's leadership in the light of Grid's theories].
Based on the understanding that leadership is a fundamental resource for nurses in health institutions, the aim of the authors was to analyze, under the light of Blake & Mouton's Grid Theories, the expectations of the Nursing team regarding nurse's leadership. The analysis was based on four investigations performed in different contexts of Brazilian Nursing and data were collected through the application of the "Grid & Leadership in Nursing Instrument" developed by Trevizan. Results show that the subjects prefer the Grid style 9.9. The authors discuss the results and emphasize the need for the development of leadership in Nursing.


The miR-15 family reinforces the transition from proliferation to differentiation in pre-B cells.
Precursor B lymphocytes expand upon expression of a pre-B cell receptor (pre-BCR), but then transit into a resting state in which immunoglobulin light chain gene recombination is initiated. This bi-phasic sequence is orchestrated by the IL-7 receptor (IL-7R) and pre-BCR signaling, respectively, but little is known about microRNAs fine-tuning these events. Here, we show that pre-B cells lacking miR-15 family functions exhibit prolonged proliferation due to aberrant expression of the target genes cyclin E1 and D3. As a consequence, they fail to trigger the transcriptional reprogramming normally accompanying their differentiation, resulting in a developmental block at the pre-B cell stage. Intriguingly, our data indicate that the miR-15 family is suppressed by both IL-7R and pre-BCR signaling, suggesting it is actively integrated into the regulatory circuits of developing B cells. These findings identify the miR-15 family as a novel element required to promote the switch from pre-B cell proliferation to differentiation.


Inhibition of local aldosterone by eplerenone reduces renal structural damage in a novel model of chronic cyclosporine A nephrotoxicity.
The fact that mineralocorticoid receptor antagonists reduce structural and functional alterations induced by cyclosporine A (CsA) indicates that aldosterone plays a key role in chronic CsA nephrotoxicity. We and other researchers have reported local renal aldosterone synthesis. To investigate local renal aldosterone's role in chronic CsA nephrotoxicity, we evaluated the effect of eplerenone (Epl) on renal structural damage and renal dysfunction in adrenalectomized (ADX) rats, and assessed whether the therapeutic benefit was associated with reduction of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), plasminogen activator inhibitor type 1 (PAI-1) and collagen I (COL-I) expression. Male Sprague-Dawley rats fed a normal-sodium diet were divided in four groups: sham-ADX, ADX, CsA, or Epl. Rats in the ADX, CsA and Epl groups were adrenalectomized first. Aldosterone, sodium and potassium levels in serum and urine were measured on the second day. Two weeks later, vehicle (sham-ADX and ADX group), CsA (25mg/kg/d), or CsA and Epl (100 mg/ kg/d) combination was administrated, respectively. After six weeks, urinary protein, creatinine clearance (Ccr), tubulointerstitial fibrosis (TIF), aldosterone level in kidney, and renal aldosterone synthase CYP11B2, COL-I, TGF-β1, CTGF and PAI-1 gene expression levels were determined. On the second day after surgery, adrenalectomized rats showed undetectable aldosterone with natriuresis, hyponatremia, decreased urinary potassium excretion and hyperpotassemia. CsA reduced Ccr, induced urinary proteins and up-regulated COL-I, TGF-β1, CTGF and PAI-1 gene expression with a significant development of TIF. Eplerenone administration prevented TIF and COL-I, TGF-β1 and PAI-1 up-regulation but did not improve renal function. Our results suggest local renal aldosterone is an important mediator of renal injury induced by CsA.


Effect of vidarabine in dimethyl sulfoxide vehicle on type 1 herpesvirus-induced cutaneous lesions in laboratory animals.
Vidarabine (9-beta-D-arabinofuranosyladenine) prepared in a 70% dimethyl sulfoxide vehicle was applied topically to type 1 herpesvirus-induced cutaneous lesions on guinea pigs and athymic nude mice. Treatments were 3 or 5 times daily for 7 days beginning 24 h after virus exposure. Against infections in guinea pigs induced by a thymidine kinase-positive virus strain, either treatment schedule effectively inhibited mean lesion score, lesion size, appearance of new lesions, and reduced lesion virus titers. Therapy was similarly effective against infections in guinea pigs induced by a thymidine kinase-negative virus strain, except that lesion virus titers were somewhat increased in animals treated 3 times daily. Treatment 5 times daily was most efficacious against both virus strains. Treatment 3 times daily of mice infected with a thymidine kinase-negative virus was not effective, but treatment 5 times daily significantly inhibited lesion score and size and reduced lesion virus titer by 37%. Toxicity controls exhibited no signs of skin irritation, although guinea pigs treated 5 times daily experienced some transient weight loss.


The accessibility of vulnerable groups to health services in Greece: a Delphi study on the perceptions of health professionals.
Problems of accessibility to healthcare services notably affect certain population groups such as poor and unemployed people, migrants and minorities, thus having a negative impact on their health. The aim of this study was to investigate these problems from the perspective of health professionals and to formulate empirically informed suggestions to solve the issue. Primary data were collected in 2010-2011 by using a panel of 36 experienced health professionals around Greece. A two-round Delphi method was undertaken to achieve the objectives of the study. The first questionnaire investigated the factors that hinder accessibility to health services. The second round aimed at determining the relative importance of each of the factors emerging in the first round. The group of experts identified 345 factors in the first round, which were grouped in 55 statements. Consensus was achieved in 22 statements. The study revealed important issues, and health professionals proposed a number of actions to eliminate the accessibility problems. The use of medical interpreters and cultural mediators, transcultural education and stronger linkages among medical facilities are important to reduce accessibility problems. Restructuring primary healthcare and better documenting of the beneficiaries could also improve the quality of provided healthcare services.


Beta blockers: the extended family.
Beta-Adrenergic blocking drugs, by occupying beta receptors without stimulating adenylate cyclase, interfere with the physiologic responses mediated by the sympathetic nervous system. This property has led to their application in the cardiovascular disorders on which sympathetic tone either underlies or contributes to the pathogenesis of the process. Lipid solubility, selective beta-receptor blockade, and intrinsic sympathomimetic activity are three additional characteristics of beta blockers that modify the pharmacodynamics and pharmacologic effects of each agent. As the role of the sympathetic nervous system in the pathogenesis of heart disease is better defined, the development of beta blockers with particular pharmacologic profiles and fewer side effects may provide more specific treatment.


Quality assurance and cancer detection rates in a provincial screening mammography program. Work in progress.
In 1990, a provincial screening program was inaugurated in Alberta, a Canadian province of 2.4 million people. The goal of the program is to decrease the number of deaths from breast cancer by 30% in women aged 50-69 years. In the first 18 months of program operations, efforts were concentrated on high levels of quality assurance in all areas of program activities. In particular, the abnormality referral rates, cancer detection rates, and size and stage of mammographically detected cancers were evaluated. Of the 9,553 women seen, 8,524 were between the ages of 50 and 69 years. Reported abnormality rates were initially more than 16%, but were brought down steadily to less than 5%. Cancer detection rates increased with age, ranging from 1.9 cancers detected per 1,000 women aged 40-49 years to 14.1 cancers per 1,000 women aged 70 years and older. Forty-one of the 61 cancers detected (67%) were less than 1.5 cm in diameter. Forty-three of the 52 cancers (83%) in which the nodal status was known were node negative. At the conclusion of the first 18 months of operation, interpretation parameters were within the target zones expected for a population-based screening program.


Trophic effect of pentagastrin on normal and regenerating parietal cells. A light and electron microscopic study in rats.
Gastric mucosal wounds were produced by cauterization of the oxyntic gland area in adult rats. From the first postoperative day, one group of animals was given two daily subcutaneous injections of pentagastrin, 250 micrograms/kg body wt, dissolved in hydrolyzed gelatin. The remaining rats served as controls and were given saline in the gelatin. After 90 days of treatment the animals were killed and the gastric mucosa was prepared for light and electron microscopy. Using stereologic techniques, data on parietal cells were obtained from both normal and regenerating mucosas. Pentagastrin induced a 2.3-fold increase in the parietal cell volume density in the regenerating mucosa and a 1.3-fold increase in normal mucosa. However, pentagastrin did not affect the ultrastructure of the parietal cells. Thus, the well-known trophic effect of pentagastrin on the gastric mucosa was confirmed; however, the absence of ultrastructural changes in the parietal cells suggests that the target for its trophic effect is likely to be the progenitor cell population.


Classical infinite-range-interaction Heisenberg ferromagnetic model: metastability and sensitivity to initial conditions.
An N-sized inertial classical Heisenberg ferromagnet, which consists of a modification of the well-known standard model, where the spins are replaced by classical rotators, is studied in the limit of infinite-range interactions. The usual canonical-ensemble mean-field solution of the inertial classical n-vector ferromagnet (for which n=3 recovers the particular Heisenberg model considered herein) is briefly reviewed, showing the well-known second-order phase transition. This Heisenberg model is studied numerically within the microcanonical ensemble through molecular dynamics. In what concerns the caloric curve, it is shown that, far from criticality, the kinetic temperature obtained at the long-time-limit microcanonical-ensemble simulation recovers well the equilibrium canonical-ensemble estimate, whereas, close to criticality, a discrepancy (presumably due to finite-size effects) is found. The time evolution of the kinetic temperature indicates that a basin of attraction exists for the initial conditions for which the system evolves into a metastable state, whose duration diverges as N--> infinity, before attaining the terminal thermal equilibrium. Such a metastable state is observed for a whole range of energies, which starts right below criticality and extends up to very high energies (in fact, the gap between the kinetic temperatures associated with the metastable and the terminal-equilibrium states is expected to disappear only as one approaches infinite energy). To the best our knowledge, this has never before been observed on similar Hamiltonian models, in a noticeable way, for such a large range of energies. For example, for the XY (n=2) version of the present model, such a behavior was observed only near criticality. It is shown also that the (metastable state) maximum Lyapunov exponent decreases with N like lambda(max) approximately N-kappa, where for the initial conditions employed herein (maximal magnetization), kappa=0.225+/-0.030, both above and below the critical point.


Circulating tumor DNA analysis detects micrometastatic disease and predicts recurrence in a patient with colon cancer: A case report.
Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide, and approximately 50% of patients with early-stage disease develop metastases. A critical limitation for successful management of CRC is early disease detection and identification of progression. Next-generation sequencing-based circulating tumor DNA (ctDNA) profiling has emerged as a promising biomarker for the assessment of minimal or molecular residual disease in CRC. The patient was initially diagnosed with resectable CRC with uncertain small lung nodules. The patient was diagnosed with sigmoid colon adenocarcinoma placed at 15 to 20 cm above the anal verge (ypT4N1R0). Lung nodules were found in the apical part of the upper lobe of the right lung and the dorsal segment of the lower lobe of the left lung. The patient received systemic therapy and local treatment and plasma ctDNA-MRD detection was performed for monitoring the molecular disease status after surgery. The patient achieved a complete response after treatment. However, he presented with disease recurrence in liver lesions. The postoperative ctDNA detection suggested the possibility of micrometastatic pulmonary disease, and that was confirmed by follow-up examination. Serial ctDNA detection revealed disease relapse ahead of radiologic imaging by a lead time of 9 months. This case demonstrated the potential of ctDNA analysis to be a sensitive and specific tool for the detection of micrometastatic disease and prediction of recurrence.


Mechanism of conversion of aspartate into glutamate in cerebral-cortex slices.
1. When slices of guinea-pig cerebral-cortex slices are incubated with [U-(14)C]-aspartate and non-radioactive glucose as substrates, the specific radioactivities of the citric acid-cycle intermediates are lower than that of the glutamate isolated from the same vessels. 2. Glutamate was significantly labelled when [1-(14)C]-aspartate and glucose were present in the incubation medium. These results would not be expected on the basis of simple conversion of aspartate into glutamate through the citric acid cycle, since the C-1 position of oxaloacetate is decarboxylated in the conversion of isocitrate into alpha-oxoglutarate. 3. It appears that aspartate is converted into glutamate by citric acid-cycle mechanisms; however, the carbon ;skeleton' is not immediately condensed with acetyl-CoA to form citrate but first follows the cycle in a reverse direction to fumarate or succinate and then proceeds in the forward direction. 4. The conversion of aspartate into glutamate appears to be compartmentalized.


The winged helix transcriptional activator HFH-3 is expressed in the distal tubules of embryonic and adult mouse kidney.
The hepatocyte nuclear factor-3 (HNF-3)/fork head homolog (HFH) proteins are an extensive family of transcription factors, which share homology in the winged helix DNA binding domain. Members of the HFH/winged helix family have been implicated in cell fate determination during pattern formation, in organogenesis, and in cell-type-specific gene expression. In this study we isolated a full-length HFH-3 cDNA clone from a human kidney library which encoded a 351-amino acid protein containing a centrally located winged helix DNA binding domain. We demonstrate that HFH-3 is a potent transcriptional activator requiring 138 C-terminal residues for activity. We used in situ hybridization to demonstrate that HFH-3 expression is restricted to the epithelium of the renal distal convoluted tubules. We determined the HFH-3 DNA binding consensus sequence by in vitro DNA binding site selection using recombinant HFH-3 protein and used this consensus sequence to identify putative HFH-3 target genes expressed there. These putative HFH-3 target genes include the Na/K-ATPase, Na/H and anion exchangers, E-cadherin, and mineralocorticoid receptor genes as well as genes for the transcription factors HNF-1, vHNF-1, and HNF-4.


Chronic kidney disease classification stratifies mortality risk after elective stent graft repair of the thoracic aorta.
Risk factors for perioperative and late mortality after thoracic endovascular aortic repair (TEVAR) remain ill-defined. In this study, we examined the prognostic significance of chronic kidney disease (CKD), a well-known predictor of death after thoracic aorta open repair, employing a stratification based on CKD stages derived from glomerular filtration rate (GFR) values. A prospective database was evaluated for 179 consecutive patients electively submitted to TEVAR between 1999 and 2007. Preoperative GFR was estimated by using the Cockcroft-Gault equation. Patient groups were stratified into four quartiles by baseline serum creatinine (SC) and GFR values, with quartile I being the lowest, and quartile IV the highest, and into the five CKD stages in reverse order (I GFR >or= 90 ml/min/1.73 m(2); II 60-89; III 30-59; IV 15-29; V < 15). Prognostic significance of preoperative GFR values and CKD stages were investigated by means of univariate and multivariate analyses, and the Kaplan-Meier log-rank method. A primary technical success was achieved in 166 of 179 patients (92.7%), and an initial clinical success in 158 (88.3%). Thirty-day mortality was 5% (nine cases). Paraplegia or paraparesis were observed in 11 (6.1%) patients, and completely resolved in six cases after cerebrospinal fluid drainage. Preoperative GFR quartiles and CKD stages were significant predictors of 30-day mortality (P = .004 and P < .0001 respectively), whereas SC quartiles did not affect the outcome (P = .12). In particular, GFR quartile I (<60 ml/min/1.73 m(2)) was associated with a ten-fold greater risk of perioperative death compared with the other three quartiles (Odds Ratio 11.4, 95% Confidence Interval 2.3-57.0, P = .003). Midterm survival was 88.8% (159 of 179) at a mean follow-up of 35.6 +/- 23.7 months. Actuarial survival at 60 months was 57.8%, 81.1%, 92.3%, and 100% for GFR quartiles I to IV respectively (P < .0001), and 0.0%, 66.7%, 59.2%, 88.6%, and 100% (P < .0001) for CKD stage V to I respectively. At univariate analyses, age (P = .019), preoperative SC quartiles (P = .001), GFR quartiles (P = .0002), and CKD stages (P < .0001) were all predictive of mid-term mortality. At multivariate Cox proportional hazards regression analysis, only CKD stages remained independently associated with the outcome (P = .008). GFR is an accurate prognostic predictor in patients submitted to TEVAR. Also, perioperative and midterm mortality directly correlate with the severity of CKD stages, allowing a risk stratification model to be employed both for risk-adjusted preoperative evaluation, and to establish accurate matching criteria for comparative studies.


[There is no Need to Reinvent the Wheel - Requirements for a Successful Project Transfer].
Although the transfer of an existing project can be a resource-efficient form of implementation of successful interventions, project transfers are rarely carried out in practice. The aim of this article is to pool the experience of 3 projects about the transfer of their prevention approaches to other municipalities and regions, as well as to make recommendations for future trans-regional transfer processes in the field of disease prevention and health promotion. To achieve this, documentation sheets were used and interviews were conducted with team members of the transfer projects. The results show that the ability to adapt intervention to context is an essential condition of successful implementation. In addition, there has to be a need for the intervention in the transfer region and a benefit to the participant organizations as well as to the team members. Furthermore, constructive and personal communication and cooperation between the participants of the original and the transferred project are required for successful transfer.


Evaluation of properties of irreversible hydrocolloid impression materials mixed with disinfectant liquids.
Addition of disinfectant to irreversible hydrocolloid impression materials can eliminate the disinfection step to avoid dimensional changes associated with it. The aim of the present study was to evaluate the effect of various disinfectant mixing liquids on the properties of commercially available irreversible hydrocolloid impression materials. Four commercially available irreversible hydrocolloid impression materials (Zelgan, Vignette, Tropicalgin, and Algitex) were mixed with disinfectant liquid containing chlorhexidine (0.1 and 0.2%) and sodium hypochlorite (0.1 and 0.5%). After mixing with disinfectant liquids, materials were evaluated for pH changes during gelation, gelation time, flow, gel strength, permanent deformation and detail reproduction. Significant changes in gelation time were observed in irreversible hydrocolloid impression materials upon mixing with disinfectant liquids. In general, chlorhexidine increased the gelation time, whereas sodium hypochlorite reduced it. However, no significant changes in the flow were observed both with chlorhexidine and sodium hypochlorite. Gel strength was found to decrease when mixed with chlorhexidine, whereas an increase in gel strength was observed upon mixing with sodium hypochlorite. Permanent deformation of the most irreversible hydrocolloid impression materials was below the specification limit even after mixing with disinfectant liquids. Sodium hypochlorite significantly reduced the surface detail reproduction, whereas no change in detail reproduction was observed with chlorhexidine. Chlorhexidine solution can be used to mix irreversible hydrocolloid impression materials in regular dental practice as it did not significantly alter the properties. This may ensure effective disinfection of impressions.


Seasonality in physical activity and walking of healthy older adults.
An increasing number of older adults require improvements in their quality of life. Physical activities, particularly walking ability, are of primary importance for older adults. The influence of season on physical activity has not been sufficiently studied among older adults. Therefore, this report compared the physical activity and walking of older individuals between summer and winter seasons using a longitudinal study design in a community in a mid-latitude area. Participants in the study comprised 39 healthy community-dwelling adults ranging in age from 65 to 80 years. Physical parameters and activities as well as the preferred speed of walking were measured at half-year intervals. Significant seasonal differences from summer to winter and from winter to summer were detected. Specifically, body fat percentage, single-leg stance, walking speed, cadence, stride length, and trunk and head-trunk pitch ranges were greater in winter than in summer, whereas grip strength and steps per day were greater in summer. Temperature and total activity level were considered to be related to body fat percentage. Grip strength was thought to be affected by outdoor temperature. The possibility of relationships between increased activity per unit time in older adults and increased preferred walking speed, cadence, and stride length in winter temperatures was discussed. The seasonal climatic environment of the geographic area of this study affected the activity level of the participants. These results indicate that seasonality should be considered when analyzing physical activity and walking in older adults.


Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity.
A growing number of youth suffer from obesity and in particular severe obesity for which intensive lifestyle intervention does not adequately reduce excess adiposity. A treatment gap exists wherein effective treatment options for an adolescent with severe obesity include intensive lifestyle modification or metabolic and bariatric surgery while the application of obesity pharmacotherapy remains largely underutilized. These youth often present with numerous obesity-related comorbid diseases, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, musculoskeletal problems, and psychosocial issues such as depression, anxiety, and social stigmatization. Current pediatric obesity treatment algorithms for pediatric primary care providers focus primarily on intensive lifestyle intervention with escalation of treatment intensity through four stages of intervention. Although a recent surge in the number of Food and Drug Administration-approved medications for obesity treatment has emerged in adults, pharmacotherapy options for youth remain limited. Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population, discussed here are the efficacy, safety, and clinical application of obesity pharmacotherapy in youth with obesity based on current literature. Legal ramifications, informed consent regulations, and appropriate off-label use of these medications in pediatrics are included, focusing on prescribing practices and prescriber limits.


Issues when treating epilepsy in the elderly.
Single seizures and epilepsy are one of the most commonly encountered neurologic disorders in elderly individuals, arising as a result of complex and often multiple acquired underlying pathologies. Ischemia is by far the most frequent etiology, and is found in up to one-third of these patients, followed by tumors, which are diagnosed in approximately 10% of affected individuals. Thus, a multidisciplinary approach to its diagnosis and management is required. Antiepileptic drug (AED) therapy is the mainstay of treatment for epilepsy in the elderly, but age-specific changes in drug metabolism, increased sensitivity to side effects, and the risk of drug interactions must be considered. Some newer AEDs seem to offer advantages over the older agents in terms of their reduced drug interaction potential (due to lack of enzyme induction), and improved tolerability profiles, which is supported by few recent clinical trials. In order to achieve seizure freedom without causing intolerable side effects, treatment should be initiated with monotherapy at low doses and titrated slowly to within the recommended dose range.


Bluetongue virus in Lebanon.
Since 2000, several incursions of bluetongue virus (BTV) occurred in the Mediterranean Basin involving European and surrounding Countries. The Middle East represents one of the most important gateways for the access of BTV in Europe. Limited data on the BTV situation in this area are available. In this perspective, an epidemiological survey on the presence of BTV in Lebanon was conducted. Of the 181 serum samples tested, 97 (mean = 53.6%; 95% CI: 46.3-60.7) resulted positive when tested for the presence of BTV antibodies by c-ELISA, of these 42 (mean = 42%; 95% CI: 32.8-51.8) serum samples were from sheep and 55 (mean = 67.9%; 95% CI: 57.1-77.1) serum samples were from goats. Fourteen blood samples (14/110; mean = 12.7%; 95% CI: 7.8-20.3), 6 (6/66; mean = 9.1%; 95% CI: 4.4-18.5) from sheep and 8 (8/44; mean = 18.2%; 95% CI: 9.6-32.0) from goats, were positive by qRT-PCR. The results with serum-neutralization assay and typing performed by RT-PCR confirmed that six BTV serotypes are currently circulating in Lebanon, and these serotypes are as follows: 1, 4, 6, 8, 16 and 24. This study is the first report that confirms the presence and circulation of BTV in Lebanon.


Rhabdomyolysis associated with simvastatin-gemfibrozil therapy.
Simvastatin is a potent inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase intended for use as a hypocholesterolemic agent. The long-term clinical experience with simvastatin indicates that it is a safe, effective, and well-tolerated hypolipidemic agent. Laboratory adverse events involving elevations of serum transaminase levels and serum creatine kinase (CK) levels to more than three times the upper limit of normal range have been seen in 1.5% and 3.4% of cases, respectively. We describe a case of severe myopathy and rhabdomyolysis associated with concomitant use of simvastatin and gemfibrozil. Seven days after discontinuing administration of gemfibrozil and simvastatin, the patient's condition improved and she was discharged home. Although this is the first report to indicate an association between myopathy and concomitant use of simvastatin and gemfibrozil, we strongly recommend caution and careful monitoring if simvastatin is given to patients receiving gemfibrozil.


Avoiding underdiagnosis, overdiagnosis, and misdiagnosis of lung carcinoma.
Given the magnitude of the therapeutic and prognostic implications, it is critical that pathologists diagnose lung cancer accurately. This can sometimes be a formidable challenge, as a number of benign entities mimic lung carcinoma and vice versa. To present strategies for recognizing benign entities likely to be confused with lung carcinoma, malignancies of the lung prone to misinterpretation as benign, and commonly misclassified pulmonary neoplasms. The medical literature and experience from consultative and surgical practice. In addition to understanding the clinical context in which a lung biopsy is procured and the radiographic findings, appreciating the histologic distribution of disease and what, if any, pathologic features are present in the background can go a long way toward averting a misdiagnosis of lung cancer. Recognizing the limitations posed by small samples and communicating clearly to clinicians the level of diagnostic uncertainty are equally as important for establishing an accurate diagnosis of lung cancer.


Spectral tuning and evolution of short wave-sensitive cone pigments in cottoid fish from Lake Baikal.
The cottoid fishes of Lake Baikal in eastern Siberia provide a unique opportunity to study the evolution of visual pigments in a group of closely related species exposed to different photic environments. Members of this species flock are adapted to different depth habitats down to >1000 m, and both the rod and cone visual pigments display short wave shifts as depth increases. The blue-sensitive cone pigments of the SWS2 class cluster into two species groups with lambda(max) values of 450 and 430 nm, with the pigment in Cottus gobio, a cottoid fish native to Britain, forming a third group with a lambda(max) of 467 nm. The sequences of the SWS2 opsin gene from C. gobio and from two representatives of the 450 and 430 nm Baikal groups are presented. Approximately 6 nm of the spectral difference between C. gobio and the 450 nm Baikal group can be ascribed to the presence of a porphyropsin/rhodopin mixture in C. gobio. Subsequent analysis of amino acid substitutions by site-directed mutagenesis demonstrates that the remainder of the shift from 461 to 450 nm arises from a Thr269Ala substitution and the shift from 450 to 430 nm at least partly from Thr118Ala and Thr118Gly substitutions. The underlying adaptive significance of these substitutions in terms of spectral tuning and signal-to-noise ratio is discussed.


Platelet size in man.
The shape and parameters of platelet size distributions were studied in 50 normal persons and 97 patients in order to test the proposed thesis that platelet size heterogeneity results mainly from aging in the circulation. This thesis was contradicted (1) by size distributions of age-homogeneous, newly-born cell populations which were lognormal with increased (instead of decreased) dispersion of volumes and (2) by the macrothrombocytosis found in some populations with normal age distribution. For these reasons, thrombocytopoiesis appeared to play the major role in determining platelet size. A model was built in which the volume variation of platelet territories due to megakaryocyte growth and membrane demarcation at each step of maturation was a random proportion of the previous value of the volume. This model explains the lognormal shape of both newborn and circulating platelet size distributions. It also implies that (1) the mean and standard deviation of platelet logvolumes depend on the rates of volume change of the individual platelet territories (growth rate minus demarcation rate) as well as on megakaryocyte maturation time; (2) platelet hyperdestruction causes an increase in the mean and dispersion of the rates of territory volume change; (3) Mediterranean macrothrombocytosis and some hereditary macrothrombocytotic thrombocytopenias or dysthrombocytopoieses reflect a diminished rate of territory demarcation, and (4) platelet size heterogeneity is caused mainly by the variations in territory growth and demarcation and not by aging in the circulation.


Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS.
Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects β-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. In a crossover design, two diets ('Standard,' STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. Thirty women with PCOS. β-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. Paired t-test indicated that the lower-CHO diet induced significant decreases in basal β-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic ('first-phase') β-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol-to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone.


Sustaining innovation and improvement in the treatment of childhood cancer: lessons from high-income countries.
Cancer in children and adolescents is rare and biologically very different from cancer in adults. It accounts for 1·4% of all cancers worldwide, although this proportion ranges from 0·5% in Europe to 4·8% in Africa, largely because of differences in age composition and life expectancy. In high-income countries, survival from childhood cancer has reached 80% through a continuous focus on the integration of clinical research into front-line care for nearly all children affected by malignant disease. However, further improvement must entail new biology-driven approaches, since optimisation of conventional treatments has in many cases reached its limits. In many instances, such approaches can only be achieved through international collaborative research, since rare cancers are being subdivided into increasingly smaller subgroups on the basis of their molecular characteristics. The long-term effect of anticancer treatment on quality of life must also be taken into account because more than one in 1000 adults in high-income countries are thought to be survivors of cancer in childhood or adolescence. The introduction of drugs that are less toxic and more targeted than those currently used necessitates a partnership between clinical and translational researchers, the pharmaceutical industry, drug regulators, and patients and their families. This therapeutic alliance will ensure that efforts are focused on the unmet clinical needs of young people with cancer. Most children with cancer live in low-income and middle-income countries, and these countries account for 94% of all deaths from cancer in people aged 0-14 years. The immediate priority for these children is to improve access to an affordable, best standard of care in each country. Every country should have a national cancer plan that recognises the unique demographic characteristics and care needs of young people with cancer. Centralisation of the complex components of treatment of these rare diseases is essential to improve survival, accelerate research, and train the future specialist workforce. Referral routes and care pathways must take account of the large geographical distances between many patients' homes and treatment centres, and the economic, cultural, and linguistic diversity of the populations served.


Role of alcohol-induced hypothermia in mediating the teratogenic effects of alcohol in C57BL/6J mice.
The purpose of this study was to determine the role of alcohol-induced maternal hypothermia in the teratogenic actions of alcohol. C57BL/6J mice were administered an acute dose of alcohol (5.8 g/kg orally) or isocaloric sucrose on day 10 of gestation. One half of each group was placed for 6 hr in an incubator set at 32 degrees C and the other half was housed in the incubator at room temperature (22 degrees C). As expected, acute prenatal alcohol exposure at this time of gestation was associated with decreased birth weight and an increase in limb and kidney malformations. The significant alcohol x environmental temperature interaction on these dependent variables indicated that the teratogenic insult was not attenuated, but was in fact even greater for the 32 degrees C/alcohol group. An absence of a main effect of environmental temperature indicated that the 32 degrees C environment, per se, was not teratogenic. Thus, maternal hypothermia is probably not an etiological factor in animal models of fetal alcohol syndrome. Moreover, antagonism of alcohol-induced maternal hypothermia exacerbates the teratogenic actions of alcohol observed at room temperature.


The common -675 4G/5G polymorphism in the plasminogen activator inhibitor -1 gene is strongly associated with obesity.
Plasminogen activator inhibitor 1 (PAI-1) increases in several insulin-resistant conditions such as obesity. We tested the hypothesis that the PAI-1 gene might be a candidate for obesity and Type II (non-insulin-dependent) diabetes mellitus. We investigated the frequency of a common and functional -675 4G/5G promoter polymorphism in the PAI-1 gene in 188 lean, 70 overweight (BMI 25-30 kg/m(2)) and 247 obese otherwise healthy Scandinavian subjects. The genotypic ( p = 0.002), or allelic ( p = 0.0004) distribution differed markedly between the three groups. Homozygosity for 4G was more common among obese people, whereas homozygosity for 5G was more common among lean subjects. Heterozygosity was evenly distributed. The lean and overweight groups did not differ in frequency distribution. The relative risk for being obese in comparison to being lean for 4G/4G was threefold higher ( p = 0.0003). Also, carriers of the 4G allele in the heterozygous or homozygous form were distributed differently between the three groups ( p = 0.006). The 4G carriers were more common among the obese than the lean group. The latter group did not differ from the overweight group. The relative risk of being obese in comparison with lean was twofold increased in 4G carriers ( p = 0.0015). Similar results were obtained in men and women. Thus, the common -675 4G/5G polymorphism in the PAI-1 gene is strongly linked to obesity and a markedly increased risk for obesity is associated with the 4G allele in its homozygous form.


[Primary aspergillus laryngitis: report of six cases].
To discuss the distinctive clinical manifestation of primary aspergillus laryngitis. Six cases of primary aspergillus laryngitis in our department were reviewed, among which 3 cases were diabetes patients, and were laryngeal mucosal barrier impairment. 2 cases were smoking, 2 cases were over use of voice and 1 case was gastro-pharyngeal reflux. Refractory hoarseness was the main clinical manifestation of all patients. The prophase treatment with antibiotics and glucocorticoid should breakdown the balance of flora and exacerbate the disease. Stop using antibiotics and glucocorticoid and alter to oral administration of itraconazole in 2 to 4 weeks after final diagnosis can effectively cure the disease. No recurrence was found in 6 month to 4 years follow up. Diffuse hyperemia, pachynsis and scattered lamellar leukasmus of vocal cord were the characteristic physical findings of primary aspergillus laryngitis. Pathology is the major means to get the final diagnosis. Oral administration of itraconazole could be effective.


Analytical Methods Based on Liquid Chromatography and Capillary Electrophoresis to Determine Neonicotinoid Residues in Complex Matrices. A Comprehensive Review.
Neonicotinoids (NNIs) are neuro-active and systemic insecticides widely used to protect crops from pest attack. During the last decades, there has been an increase concern about their uses and toxic effects, especially to beneficial and non-target insects such as pollinators. To assess potential health hazards and the environmental impacts derived from NNIs uses, a great variety of analytical procedures for the determination of their residues and their metabolites at trace level in environmental, biological and food samples have been reported. Due to the complexity of the samples, efficient sample pretreatment methods have been developed, which include mostly clean-up and preconcentration steps. On the other hand, among the analytical techniques used for their determination, high-performance liquid chromatography (HPLC) coupled to ultraviolet (UV) or mass spectrometry (MS) detection is the most widely used, although capillary electrophoresis (CE) has also been employed in the last years, considering some improvements in sensitivity when coupling with new MS detectors. In this review, we present a critical overview of analytical methods based on HPLC and CE reported in the last decade, discussing relevant and innovative sample treatments for the analysis of environmental, food and biological samples.


Quantitative regional cerebral blood flow measurement techniques improve noninvasive detection of cerebrovascular vasospasm after aneurysmal subarachnoid hemorrhage.
Adequate therapy of vasospasm (VS) in patients suffering from aneurysmal subarachnoid hemorrhage critically depends upon early and reliable diagnosis of cerebral hypoperfusion. The objective of the present study was to evaluate the usefulness of quantitative regional blood flow (rCBF) analysis as an adjunct in noninvasive prediction of VS. Therefore, 33 transcranial Doppler sonography (TCD) studies assuming cerebrovascular VS (TCD flow velocity >120 cm/s) were followed by (s)Xe/CT and cerebral panangiography (PA). TCD plus (s)Xe/CT significantly increased the predictability of VS from 34 to 91%, proving that a combination of TCD and rCBF studies improves the noninvasive detection of VS and might help to prevent unnecessary angiographic examinations.


Toward integrase defective lentiviral vectors for genetic immunization.
Genetic immunization with lentiviral vectors is under evaluation as a means for induction of sustained immune response. Lentiviral vectors showed reduced antivector immune responses and efficiently transduce post-mitotic cells in vivo, including antigen presenting cells, such as dendritic cells and macrophages, thus providing a significant benefit over other vector-based antigen delivery platforms. Several evidences indicate that a single immunization with lentiviral vectors induces strong and sustained effector and memory T-cell immune responses, as well as antibody production. New generation of lentiviral vectors with improved biosafety profile are also under development. In particular, integration defective lentiviral vectors have been generated and used as an efficient and safe delivery system for both gene therapy and immunization purposes. Taken together, these evidences support the ongoing development of lentiviral vector-based genetic immunization strategies for safe applications in the clinic.


Introduction to the theme.
Spicker introduces a set of five articles on medico-economic, ethical, and conceptual problems raised by the new Medicare prospective payment system (PPS), which bases reimbursement of hospitals on treatment of patients in disease categories known as diagnosis related groups (DRGs). The articles are by Charles E. Begley ("Prospective payment and medical ethics"); George J. Agich ("Incentives and obligations under prospective payment"); Thomas Halper ("DRGs and the idea of a just price"); Leonard M. Fleck ("DRGs: justice and the invisible rationing of health care resources"); and Edmund L. Erde ("Efficiency, ethics and indigent care: a review of the proceedings of the conference 'The all-payers DRG system: has New Jersey found an efficient and ethical way to provide indigent care?").


Anterior Chamber Migration of Ozurdex Implants.
We present patient characteristics and follow-up results of cases with anterior chamber dexamethasone implant migration. The common feature of all six presented cases was vitrectomized eyes. Four of the patients had sutured intraocular lens (IOL) implantation due to complicated cataract surgery, one had combined retinal detachment surgery with sutured IOL implantation, and one had vitrectomy for diabetic intravitreal hemorrhage cleaning and uncomplicated cataract surgery. Anterior chamber implant migration caused corneal edema in all cases and elevated intraocular pressure in three cases. In two cases, the dexamethasone implant was directed into the vitreous cavity after maximum pupillary dilation and corneal manipulation with cotton tip applicator with the patient in reverse Trendelenburg position. There was no other complication until dexamethasone implant degradation, with clear cornea at final examination. In two cases, the implant was removed from the anterior chamber by aspiration, but keratoplasty surgery was planned due to endothelial cell loss and persistent corneal edema during follow-up. In the last two cases, the dexamethasone implant was redirected into the vitreous chamber with a 23-gauge catheter and anterior chamber maintainer but they migrated into the anterior chamber again. In one of these patients, the implant was aspirated by catheter and corneal transplantation was performed due to corneal edema, while the other patient's implant was redirected into the vitreous chamber with no further anterior migration. The risk of dexamethasone implants migrating into the anterior chamber of vitrectomized eyes and those with sutured IOL implantation should be kept in mind and the patient should be informed and advised to see an ophthalmologist immediately before permanent corneal endothelial damage occurs.


The assessment and impact of sarcopenia in lung cancer: a systematic literature review.
There is growing awareness of the relationship between sarcopenia (loss of muscle mass and function), and outcomes in cancer, making it a potential target for future therapies. In order to inform future research and practice, we undertook a systematic review of factors associated with loss of muscle mass, and the relationship between muscle function and muscle mass in lung cancer, a common condition associated with poor outcomes. We conducted a computerised systematic literature search on five databases. Studies were included if they explored muscle mass as an outcome measure in patients with lung cancer, and were published in English. Secondary care. Patients with lung cancer. Factors associated with loss of muscle mass and muscle function, or sarcopenia, and the clinical impact thereof in patients with lung cancer. We reviewed 5726 citations, and 35 articles were selected for analysis. Sarcopenia, as defined by reduced muscle mass alone, was found to be very prevalent in patients with lung cancer, regardless of body mass index, and where present was associated with poorer functional status and overall survival. There were diverse studies exploring molecular and metabolic factors in the development of loss of muscle mass; however, the precise mechanisms that contribute to sarcopenia and cachexia remain uncertain. The effect of nutritional supplements and ATP infusions on muscle mass showed conflicting results. There are very limited data on the correlation between degree of sarcopenia and muscle function, which has a non-linear relationship in older non-cancer populations. Loss of muscle mass is a significant contributor to morbidity in patients with lung cancer. Loss of muscle mass and function may predate clinically overt cachexia, underlining the importance of evaluating sarcopenia, rather than weight loss alone. Understanding this relationship and its associated factors will provide opportunities for focused intervention to improve clinical outcomes.


Transmissive resonator optic gyro based on silica waveguide ring resonator.
A transmissive resonator optic gyro (TROG) based on silica waveguide ring resonator with improved long-term bias stability is reported in this paper. The modeling of a transmissive resonator used in optic gyro is carried out. The polarization dependence of resonator and the influences of phase modulator's residual intensity modulation on the gyro output are analyzed. The resonator is simulated, designed, fabricated, tested and used to build up a TROG prototype. A bias stability of 0.22°/s over one hour test with an integration time of 10s is successfully demonstrated. No obvious drift has been found from the Allan variance analysis result of a 10000s test data, which means that the TROG prototype has an improved long-term drift characteristic.


A rationale for modifying the site of insertion of the orticochea pharyngoplasty.
A modification of the insertion level of Orticochea flaps is proposed. The purpose of the modification is to place the pharyngoplasty at a higher site, in the area of attempted velopharyngeal contact. The site of velopharyngeal contact can be identified using lateral radiographic techniques. A success rate of 93 percent was achieved in improved oral-nasal resonance balance when the pharyngoplasty was placed at a site in the nasopharynx.


Estimation of the components of municipal solid waste settlement.
Estimation of the municipal solid waste settlements and the contribution of each of the components are essential in the estimation of the volume of the waste that can be accommodated in a landfill and increase the post-usage of the landfill. This article describes an experimental methodology for estimating and separating primary settlement, settlement owing to creep and biodegradation-induced settlement. The primary settlement and secondary settlement have been estimated and separated based on 100% pore pressure dissipation time and the coefficient of consolidation. Mechanical creep and biodegradation settlements were estimated and separated based on the observed time required for landfill gas production. The results of a series of laboratory triaxial tests, creep tests and anaerobic reactor cell setups were conducted to describe the components of settlement. All the tests were conducted on municipal solid waste (compost reject) samples. It was observed that biodegradation accounted to more than 40% of the total settlement, whereas mechanical creep contributed more than 20% towards the total settlement. The essential model parameters, such as the compression ratio (Cc'), rate of mechanical creep (c), coefficient of mechanical creep (b), rate of biodegradation (d) and the total strain owing to biodegradation (EDG ), are useful parameters in the estimation of total settlements as well as components of settlement in landfill.


Biocompatible Short-Peptides Fibrin Co-assembled Hydrogels.
Fibrin hydrogels made by self-assembly of fibrinogen obtained from human plasma have shown excellent biocompatible and biodegradable properties and are widely used in regenerative medicine. The fibrinogen self-assembly process can be triggered under physiological conditions by the action of thrombin, allowing the injection of pregel mixtures that have been used as cell carriers, wound-healing systems, and bio-adhesives. However, access to fibrinogen from human plasma is expensive and fibrin gels have limited mechanical properties, which make them unsuitable for certain applications. One solution to these problems is to obtain composite gels made of fibrin and other polymeric compounds that improve their mechanical properties and usage. Herein, we prepared composite hydrogels made by the self-assembly of fibrinogen together with Fmoc-FF (Fmoc-diphenylalanine) and Fmoc-RGD (Fmoc-arginine-glycine-aspartic acid). We have shown that the mixture of these three peptides co-assembles and gives rise to a unique type of supramolecular fiber, whose morphology and mechanical properties can be modulated. We have carried out a complete characterization of these materials from chemical, physical, and biological points of view. Composite gels have improved mechanical properties compared to pure fibrin gels, as well as showing excellent biocompatibility ex vivo. In vivo experiments have shown that these gels do not cause any type of inflammatory response or tissue damage and are completely resorbed in short time, which would enable their use as vehicles for cell, drug, or growth factor release.


Red blood cell mechanical stability test.
Red blood cells (RBC) are exposed to various levels of shear stress (SS) during their flow in the circulatory system, yet no significant damage occurs if their mechanical stability is not impaired. Alternatively, normal RBC may be damaged during flow in non-physiological environments and under extreme SS (e.g., extracorporeal circulation, ventricular assist devices). The shear-induced damage may result in hemolysis or in altered mechanical properties of RBC that, in turn, reduces the ability of RBC to withstand further damage by SS. An ektacytometer employing a Couette shearing system was used to apply SS at a constant level of 100 Pa for 300 seconds as a model of sub-hemolytic mechanical stress. The degree of cellular damage during and after the application was assessed by diffraction pattern analysis. The area of the diffraction pattern was found to correlate with the number of RBC in the sheared suspension. Monitoring the ellipse area during the application of gradually increasing SS provides the concentration of the remaining intact RBC and can therefore be used to estimate the hemolytic threshold as a measure of RBC mechanical stability. The hemolytic threshold determined after the mechanical stress application was found to be ~150 Pa, while it was ~250 Pa in the same samples before the SS application. Additionally, SS-elongation index curves recorded before and after the application of the sub-hemolytic SS significantly differed from each other, indicating the impairment in deformability following the mechanical stress. The Couette type ektacytometer can be used as a tool to assess the sub-hemolytic damage to RBC in testing the biomedical equipment.


Surface-initiated anionic polymerization of [1]silaferrocenophanes for the preparation of colloidal preceramic materials.
A novel strategy for the preparation of poly(ferrocenylsilane) (PFS) immobilized on the surface of cross-linked polystyrene (PS) nanoparticles is reported. The ferrocene-containing core/shell architectures are shown to be excellent candidates as preceramic polymers yielding spherical ceramic materials consisting of iron silicide (Fe3 Si) and metallic iron after thermal treatment. For this purpose, dimethyl- and hydromethyl[1]silaferrocenophane monomers are polymerized by surface-initiated ring-opening polymerization upon taking advantage of residual vinylic moieties at the PS particle surface. A strategy for selective chain growth from the particle surface is developed without the formation of free PFS homopolymer in solution. The grafted particles are characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). These particles are excellent precursors for ceramics as studied by thermogravimetric analysis (TGA). The composition of the ceramics is studied using X-ray diffraction (XRD) measurements, while the morphology is probed by scanning electron microscopy (SEM) revealing the original spherical shape of the precursor particles. Obtained ceramic materials- predominantly based on iron silicides-show ferromagnetic behavior as investigated by superconducting quantum interference device (SQUID) magnetization measurements at different temperatures.


Anaphylaxis following the use of bacitracin ointment. Report of a case and review of the literature.
A 52-year-old woman suffered an acute anaphylactic reaction to topically applied bacitracin. An investigation disclosed the presence of concurrent type I and IV hypersensitivity to bacitracin. We review five other cases of anaphylactic reactions to topical medications and describe the clinical characteristics common to all six cases.


Cardiorespiratory Fitness as a Mediator of the Influence of Diet on Obesity in Children.
The association between diet and obesity has been widely studied and it continues to be controversial; however, the extent to which cardiorespiratory fitness (CRF) acts as a confounder or mediator in this relation has not been analyzed. The aim of this study is to examine if the relation between diet and obesity is mediated by CRF. In this cross-sectional study, fat mass (by electronic bioimpedance) was measured in 320 schoolchildren, aged 9-11 years. Diet was measured through two computerised 24-h dietary recalls and CRF was assessed by the 20-m shuttle run test. Simple mediation analyses were fitted. CRF acts as a partial mediator in the negative relationship between dietary factors (energy intake/weight, carbohydrate intake/weight, protein intake/weight, and fat intake/weight) and fat mass. The percentage of mediation ranged from 24.3 to 33.2%. Thus, Spanish schoolchildren with higher levels of energy and macronutrients intake had lower adiposity levels, especially when they had good levels of CRF.


Mentalization-based treatment and its evidence-base status: A systematic literature review.
This study reviewed the evidence-base status of mentalization-based treatment (MBT), its quality, strengths, and limitations. The aim was to pave the way for further MBT research. An electronic database and reference lists search identified MBT outcome papers, and these were systematically reviewed. The quality of the studies and the risk of bias were determined using two validated checklist tools. Twenty-three studies were included in the review. This included nine randomized controlled trials, seven uncontrolled pre- and post-effectiveness studies, three retrospective cohort studies, two uncontrolled randomized trials, and two case studies. The methodological quality of almost half of the papers was assessed as fair (43%), followed by good (34%), poor (17%), and excellent (4%) ratings. Nevertheless, the review identified risk of confounding bias across the majority of studies (60%) and fidelity to treatment was poorly reported in almost half of the studies (47%). Most of the studies focused on borderline personality disorder (BPD), showing positive clinical outcomes for this population but the evidence-base for other presentations was still developing. The treatment of adolescents who self-harm and at-risk mothers in substance abuse treatment showed particularly promising results, as these are client groups that have previously shown limited positive response to psychological interventions. Mentalization-based treatment is a potentially effective method across a wide range of clinical presentations but further research should focus on increasing the quality and the quantity of the MBT evidence outside the treatment of BPD. MBT can be a particularly effective intervention for the treatment of adults with a diagnosis of BPD and of adolescents who self-harm and mothers enrolled in substance abuse treatments. MBT can be an effective intervention for depression and eating disorders but the evidence is currently limited. Professionals supporting mothers of children at risk may benefit from receiving training in the principles of MBT.


Orlistat (The Lipase Inhibitor) Therapy in Overweight and Obese Subfertile Women.
This experimental study was carried out to evaluate the efficacy of orlistat (a pancreatic lipase inhibitor) therapy over lifestyle change on weight reduction and ovulation in overweight and obese subfertile women. It was carried out in Department of Gynecology and Obstetrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, Bangladesh from August 2015 to January 2016. Subfertile obese and overweight female patients attending the study centre during study period was considered as study population. Subfertile women with normozoospermic husband with BMI (25-40) Kg/M2, age (18-35) years with no history of taking medication or dietary modification for weight loss currently or for the preceding 3 months were included in this study but subfertile patients having laparoscopic ovarian drilling and metformin and those with structural abnormalities in reproductive tract and known hormonal and medical disorder were excluded from this study. Detailed history taking, physical examination including weight, Body Mass Index (BMI) and baseline relevant investigations were done. Transvaginal sonography (TVS) on day 12 and day 14 of menstrual cycle was done for evaluation of ovulatory status of the patients. Counseling was done about life style change by diet of low glycemic index and moderate exercise. Following written informed consent, 120 patients were enrolled into either of the two groups. Group I received capsule Orlistat 120 mg twice daily for 3 months period. Group II was counseled for life style modification only. Post treatment weight measurement and TVS on day 12 and 14 were done after completion of intervention. Then pre and post-treatment parameters were assessed between two groups. Mean age was (27.31±4.58) years in Group I and (26.20±4.71) years in Group II. Majority patients, (78.3%) in Group I and (76.7%) in Group II had oligomenorrhoea. Hirsuitism was observed in (25%) in Group I and (43.3%) in Group II. Mean weight (kg) at booking was (72.26±7.81) in Group I and (67.10±5.93) in Group II; after 3 months (67.77±7.82) and (63.55±6.07). Reduction of weight (%): (6.52±2.28) in Group I and (5.33±2.14) in Group II which was significantly higher in Group I than that of Group II in (25.0-29.9) BMI. Ovulation assessed by TVS at booking and after 3 months in Group I: 13(21.7%) and 37 (61.7%) and in Group II: 14 (23.3%) and 27 (45.0%). Ovulation was higher in Group I than that of Group II, but the difference was not statistically significant. Majority of the overweight and obese subfertile patients suffered from oligomenorrhoea and anovulation. Weight significantly reduced in both groups along with ovulation improvement, more in Group I, but insignificant in between groups. Therefore this study suggested that orlistat can improve ovulation as it acts indirectly by weight reduction more than life style modification alone.


Rapid preparative isolation of a new phenylpropanoid glycoside and four minor compounds from Sparganium stoloniferum using high-speed counter-current chromatography as a fractionation tool.
A rapid high-speed counter-current chromatography (HSCCC) method was used to isolate five minor compounds from rhizome of Sparganium stoloniferum namely San Leng in Chinese, including two phenylpropanoid glycosides, sparganiaside A (1) and 1-O-feruloyl-3-p-coumaroylglycerol (2), and three aromatic acids, vanillic acid (3), p-hydroxylcinnamic acid (4), and p-hydroxybenzoic acid (5), of which, compound 1 was a new one. Five compounds were preparatively enriched at top efficiency by one-step HSCCC operation in the isolation procedure. A suitable solvent system composed of chloroform-methanol-water (4:3.5:1.8, v/v/v) was used. And the operation time was less than 4 h. The purities of compounds (1-5) in the enriched fractions were determined to be 75.8%, 66.3%, 90.6%, 79.9%, and 98.2%, respectively. The mean recoveries of the five compounds were 84.8%, 87.3%, 81.8%, 90.3%, and 92.7%, respectively. Compounds 1-4 were further purified by semi-preparative high-performance liquid chromatography (HPLC). This is the first report on the use of HSCCC as a fractionation tool for preparative isolation of minor compounds from S. stoloniferum. The method was proved to be rapid, convenient, high yield, and low cost. HSCCC was shown to be a quick and effective tool in isolation of natural products even though the compounds were not abundant.


The sense of life satisfaction versus dietary choices of young women doing fitness for recreational purposes
: The health potential of a person can be improved thanks to recreational physical activity and rational diet. The sense of life satisfaction is also one of significant health resources. The aim of the study was to analyze the relations between the level of life satisfaction and the frequency of consuming selected products in the group of young women who engage in fitness for recreational purposes. The study involved 200 young women (20-30 years old) who regularly do recreational physical activity in fitness clubs in Małopolska. An original questionnaire was used to measure the frequency of consumption of food products, with the following scale: several times a day, once a day, several times a week, once a week, several times a month, and more rarely / never. The Satisfaction With Life Scale (SWLS) by Diener et al., adapted into Polish by Juczyński, was used to measure life satisfaction. The results were analyzed with the use of U Mann-Whitney test and Spearman's rank correlation coefficients in a statistical package PQStat ver. 1.6. Statistical analysis showed that along with higher life satisfaction, women significantly less often consumed: white bread (p<0.05) and whole milk (p<0.05), and significantly more often: wholemeal bread (p<0.05), whole-grain rice and pasta (p<0.001), legumes (p<0.05), fermented milk products (p<0.05), fish (p<0.05), seafood (p<0.01), beef (p<0.01) and vegetable juices (p<0.001). The comparison of the mean frequency of consumption of certain foods depending on the level of life satisfaction (low vs. high according to the SWLS) showed that women who displayed high life satisfaction significantly more often consumed wholemeal bread (p<0.01), whole-grain rice and pasta (p<0.001), curd cheese with reduced fat content (p<0.05), seafood (p<0.05), beef (p<0.001) and vegetable juices (p<0.05), and significantly less often, sweets and confectionery (p<0.05) than did women displaying low life satisfaction. The study proved the predictive role of life satisfaction in the development of eating habits of young, physically active women, indicating more rational dietary choices of women with higher levels of this individual quality.


[Demographic change and disease rates: a projection until 2050].
Demographic change and its impact on the German healthcare system is a subject of great debate. The purpose of this paper is to make projections on disease rates based on the 11th coordinated demographic prediction and population-based data which take into consideration demographic developments. The German population will decrease by approximately 16% until 2050, while at the same time the number of persons aged over 65 years will increase by 38% and the number of individuals aged over 80 years will increase by 156%. Baby boomers cause a vertical wave in the population pyramid. The population pyramid itself will lead to an overproportional increase in the number of elderly persons. Assuming that disease probability stays the same, the incidence of diseases due to advanced age will rise dramatically. Especially diseases, such as community-acquired pneumonia, age-related macula degeneration, dementia, fracture of the femur neck, and myocardial infarction, will by then occur more often. By 2050, some of the most frequent diseases will be hypertension and arthrosis. Thus, the continuous cutting of resources seems rather short minded. It is highly recommended to reconsider the long-run effects before setting a health policy course. A proper social discourse about primary care and prioritization appears to be urgently needed.


Electrically variable liquid crystal lenses for ophthalmic distance accommodation.
We present the example of a specific design of an electrically tunable liquid crystal lens (TLCL) with floating electrode to analyze experimentally the potential of using TLCLs in intraocular implants. An optimized voltage-frequency driving technique is demonstrated to achieve high optical powers (up to 4 diopters) with very low aberrations (below 0.1μm) for an optical aperture of 3mm. In addition, the continuous character of distance accommodation and the absence of granularity across the aperture of the lens (pixel-free) make this component an excellent choice for various ophthalmic applications.


[Structural organization of the genome of paramyxoviruses].
The review summarizes the recent papers on the studies of primary structure of genome of a number of paramyxoviruses from the three genera of a family. The cited data demonstrate that despite the common principles of the genetic material arrangement shared by paramyxoviruses, they are variable in the genome, the primary structure of intragenic region, as well as the strategy of coding for some proteins. The data on the arrangement of the genetic material is discussed as useful as a criterion for classification of single stranded viruses with unsegmented genome.


Effect of endovascular coronary low-level laser therapy during angioplasty on the release of endothelin-1 and nitric oxide.
Nitric oxide (NO) and endothelin-1 are potentially significant factors contributing to the pathogenesis of post-angioplasty restenosis. It may be postulated that low-level laser therapy (LLLT) can favorably influence the process of restenosis by affecting those factors. The aim of the study was to evaluate the effect of LLLT applied during percutaneous coronary intervention (PCI) on the factors participating in the homeostasis of vascular tone - NO and endothelin-1. In a randomized, prospective study of 52 subjects undergoing PCI, an additional 808 nm intravascular LLLT was applied at a dose of 9 J/cm2 in the lesion part. The control group was 49 subjects with PCI only. We assessed the concentration of nitrites/nitrates reflecting NO metabolism as well as endothelin-1 in both groups before PCI, and at 6 h, 12 h and 1 month after the procedure. In addition, half a year after PCI, a follow-up angiography was performed. Statistically higher nitrite/nitrate concentrations were observed in the laser group as compared to the control group in all tests except the pre-PCI assays. Endothelin-1 levels were significantly higher in the laser group 6 h after PCI with a significant decrease in subsequent tests, which was not observed in the control group. The restenosis rate was 15.0% in the laser group and 32.4% in the control group (however the difference was not statistically significant). LLLT applied during the PCI procedure can influence the process of restenosis by modifying NO and endothelin-1 concentrations.


What Works in Collaboration? Identifying Key Ingredients to Improve Service Delivery in Schools.
This survey study examined factors that may influence interprofessional collaboration in schools to support children with oral and written language impairments, namely, knowledge, collaborative beliefs and practices, and resources. A survey was conducted across 319 school-based professionals, in a partnering public school district, to examine these constructs within the context of each individual participant's professional role. Between-groups comparisons were made between special educators, general educators, paraprofessionals, and indirect educators (i.e., those whose roles do not explicitly include language-based instruction). Special educators had significantly higher levels of learning experiences and knowledge about language disorders compared to other groups. Those who engaged in the most independent learning (i.e., learning outside of pre- or in-service learning) exhibited the highest levels of knowledge. Collaborative beliefs among professionals were best predicted by access to resources and overall professional learning experiences. More positive collaborative beliefs, in turn, predicted higher rates of collaborative behaviors. Resources were predicted by a small negative relationship with years of experience and by working in specific school buildings within the district. Those with less experience in specific buildings reported more resources. Individuals with higher levels of individual learning and positive attitudes toward collaboration may enhance the interprofessional collaborative practices of teams supporting children with language disorders. https://doi.org/10.23641/asha.24059178.


Amplitude spectral area: predicting the success of electric shock delivered by defibrillators with different waveforms.
Prolonged ventricular fibrillation (VF) is associated with a low rate of return of spontaneous circulation (ROSC) following electric shock. Moreover, electric shock that does not reestablish spontaneous circulation causes myocardial dysfunction even if ROSC is subsequently achieved. Amplitude spectral area (AMSA), calculated by analysis of VF waveforms immediately before electric shock, is considered to predict the outcome of electric shock. This study aimed to evaluate the prognostic value of AMSA in relation to waveforms of defibrillators in prehospital settings. The AMSA values of 81 patients with VF confirmed by ambulance crews were compared according to the type of defibrillators with different waveforms and between those with and without ROSC. With a biphasic defibrillator, the mean AMSA was significantly different between the 14 patients who achieved ROSC (25.3 ± 9.5 mV-Hz) and the 43 subjects who did not achieve ROSC (15.4 ± 8.1 mV-Hz; p = 0.0006). No significant difference was seen in the corresponding values when a monophasic defibrillator was used, at 19.1 ± 2.4 mV-Hz for 3 ROSC patients and 16.1 ± 7.5mV-Hz for 21 non-ROSC patients. AMSA may serve as a predictive measure for ROSC following electric shock delivered by a biphasic defibrillator.


Toxic exposure of children in 2004--telephone service of toxicology.
509 toxicological telephone inquiries concerning children under 15 years have been provided by Kraków Poison Information Centre (PIC) in the year 2004. Medication drugs were involved in almost one half (n=208) the cases noted. 63.7% of calls concerned children under 4 years with a two-year-old group predominance. The main reason for poisoning in children under 4 were pharmaceuticals (42.6%), followed by pesticides (9.8%), corrosives (8.8%), hydrocarbons (8.1%), plants (5.5%) and detergents (3.7%); all exposure were accidental. Suicide attempts reached 32.3% in the 12-14 age group. In that group also a cases of psychoactive substances overdosing were noted. Most exposures in children reported to poison centre were accidental (87.2%). Thus, it is absolutely necessary to intensify prevention and education activity both for parents and primary school children to avoid the poisoning.


Betulin-Constituted Multiblock Amphiphiles for Broad-Spectrum Protein Resistance.
Multiblock-like amphiphilic polyurethanes constituted by poly(ethylene oxide) and biosourced betulin are designed for antifouling and synthesized by a convenient organocatalytic route comprising tandem chain-growth and step-growth polymerizations. The doping density of betulin (DB) in the polymer chain structure is readily varied by a mixed-initiator strategy. The spin-coated polymer films exhibit unique nanophase separation and protein resistance behaviors. Higher DB leads to enhanced surface hydrophobicity and, unexpectedly, improved protein resistance. It is found that the surface holds molecular-level heterogeneity when DB is substantially high due to restricted phase separation; therefore, broad-spectrum protein resistance is achieved despite considerable surface hydrophobicity. As DB decreases, the distance between adjacent betulin units increases so that hydrophobic nanodomains are formed, which provide enough landing areas for relatively small-sized proteins to adsorb on the surface.


Difference in adenoma detection rates according to colonoscopic withdrawal times and the level of expertise.
Adequate screening colonoscopy in the general population decreases the mortality associated with colorectal cancer through detection and removal of adenomatous polyps. Prolonged colonoscopic withdrawal times (>6 min) are reportedly beneficial for adenoma detection rates (ADRs). However, the quality of the endoscopist compared with colonoscopic withdrawal times is not known. The aims of this study were to investigate the difference in ADRs between trainees and experienced examiners. A total of 967 consecutive patients who underwent screening colonoscopy in a single University hospital from June 2010 to November 2011 were enrolled in this prospective observational study. Colonoscopy was performed by four experienced staff and seven gastroenterology fellows. Seven gastroenterology fellows performed 633 colonoscopies and four experienced staff performed 334 colonoscopies. The overall detection rates of colorectal adenoma were 31.5% with ADRs of fellows and staff of 29.4% and 35.6%, respectively (p=0.047). Fellows also showed lower advanced ADRs (5.7% vs. 9.9%, p=0.016), and fellows had longer mean withdrawal times than staff (12.4±B1;4.9 min vs. 8.2±B1;4.1 min, p<0.001). Multivariate analysis showed significantly increased ADRs and advanced ADRs for staff compared with fellows (adjusted OR 2.41, 95% CI 1.70-3.43; adjusted OR 2.55, 95% CI 1.47-4.45, respectively). ADRs were significantly lower when colonoscopy was performed by trainees, although withdrawal times were longer than those of staff. Our results demonstrated that the quality of colonoscopy, as measured by ADRs, may be improved by experienced examiners.


Nailing down a diagnosis.
Nails can act as a barometer of an individual's health, offer clues to nutritional disturbances and serve as windows through which to view capillary changes associated with constitutional disease. Understanding growth and development of normal nails is essential to the identification and interpretation of nail pathology. Causes of onychopathology include genetic disease, trauma, tumors, dermatologic disease, miscellaneous acquired disorders and generalized systemic disease. Diagnosis is aided by the realization that the nails have a limited number of reaction patterns when disturbed by disease. Any of these reactions may manifest a host of disorders. Clinicians should remember to include the nails in patient assessment. The nails are interesting anatomical and physiological areas that can help make a diagnosis.


[A clinical comparative study of multiple sclerosis and neuromyelitis optica.].
To compare the clinical characteristics of multiple sclerosis (MS) and neuromyelitis optica (NMO) for better diagnosis and differential diagnosis of them. The characteristics of 40 MS and 38 NMO cases were retrospectively studied on clinic manifestations, electroneurophysiology, some laboratory indices, imaging characteristics and so on. The ratios of male to female were 1:1.35 and 1:4.43 respectively in patients with MS and NMO, so patients with NMO were more likely to be female as compared with MS (P < 0.05). The mean onset age was (35.5 +/- 13.9) years in MS patients and (30.6 +/- 15.6) years in NMO patients, but no significant difference was found (P > 0.05). The cases of visual acuity </= 0.1 in patients NMO was 13, which of MS was merely 1. The cases of visual acuity less than 0.5 after treatment in NMO patients was 19, which in MS was only 1. The cases of cognitive impairment in NMO was 3, which of MS was 10. The cases of cerebrospinal fluid oligoclonal bands in MS was 16, which in NMO patients was 9. The lesions of spinal cord shown in MRI of MS patients were typically oval, peripheral and asymmetric, but those in NMO patients extended longitudinally and converged centrally. The mean number of involved vertebral segments in NMO patients was significantly greater than that in MS patients (6.6 vs 2.2, P < 0.01). Furthermore, the number of spinal cord lesions in MS patients was alse remarkably greater than that in NMO patients (2.0 vs 1.2, P < 0.01). NMO may be a distinct clinical entity, which is likely to be differentiated from MS by its tendency to affect women, younger age at onset, and other features clinical manifestations, electroneurophysiology, laboratory parameters, neuroimaging show.


Promoting Self-Care of Diabetic Foot Ulcers Through a Mobile Phone App: User-Centered Design and Evaluation.
Without effective self-care, people with diabetic foot ulcers (DFUs) are at risk of prolonged healing times, hospitalization, amputation, and reduced quality of life. Despite these consequences, adherence to DFU self-care remains low. New strategies are needed to engage people in the self-care of their DFUs. This study aimed to evaluate the usability and potential usefulness of a new mobile phone app to engage people with DFUs in self-care. We developed a new mobile phone app, MyFootCare, to engage people with DFUs through goals, progress monitoring, and reminders in self-care. Key features included novel visual analytics that automatically extract and monitor DFU size information from mobile phone photos of the foot. A functional prototype of MyFootCare was created and evaluated through a user-centered design process with 11 participants with DFUs. Data were collected through semistructured interviews discussing existing self-care practices and observations of MyFootCare with participants. Data were analyzed qualitatively through thematic analysis. Key themes were as follows: (1) participants already used mobile phone photos to monitor their DFU progress; (2) participants had limited experience with using mobile phone apps; (3) participants desired the objective DFU size data provided by the tracking feature of MyFootCare to monitor their DFU progress; (4) participants were ambivalent about the MyFootCare goal image and diary features, commenting that these features were useful but also that it was unlikely that they would use them; and (5) participants desired to share their MyFootCare data with their clinicians to demonstrate engagement in self-care and to reflect on their progress. MyFootCare shows promising features to engage people in DFU self-care. Most notably, ulcer size data are useful to monitor progress and engage people. However, more work is needed to improve the usability and accuracy of MyFootCare, that is, by refining the process of taking and analyzing photos of DFUs and removing unnecessary features. These findings open the door for further work to develop a system that is easy to use and functions in everyday life conditions and to test it with people with DFUs and their carers.


The endocyclic restriction test: the geometries of nucleophilic substitutions at sulfur(VI) and sulfur(II).
The trajectories for nucleophilic substitutions at sulfur(VI) and sulfur(II) have been investigated by the endocyclic restriction test. On the basis of double-labeling experiments, the sulfur(VI) transfer in the conversion of 1 to 2 is found to be intramolecular, while the sulfur(VI) transfer in the conversion of 3 to 4 and the sulfur(II) transfer in the conversion of 5 to 6 are found to be intermolecular. These results are taken to be consistent with transition structures for these sulfur transfer reactions which require a large angle between the entering and leaving group, a geometry analogous to apical group positions in trigonal bipyramidal transition states.


Sensitization by ventral pallidal DAMGO: lack of cross-sensitization to morphine.
Repeated injections of morphine into the ventral pallidum of laboratory rats results in the development and expression of motor sensitization. Although morphine and [D-Ala, N-MePhe, Gly(ol)]-enkephalin (DAMGO) both activate μ-opioid receptors, their influence on receptor-mediated signaling differs; therefore, we determined if they differentially influenced ventral pallidal-mediated motor sensitization. Repeated intraventral pallidal injections of DAMGO led to the development of motor sensitization and this behavior persisted for at least 18 days. When DAMGO-sensitized rats were challenged with a morphine treatment (either in the ventral pallidum or systemically), the resulting motor response was similar to that seen in rats with a history of intrapallidal saline, that is, cross-sensitization did not occur. As DAMGO and morphine likely activate different arms of the heterologous signal transduction system associated with μ-opioid receptors, these observations may reflect behavioral consequences of biased agonism at these receptors.


Hard Magnetic Properties and the Features of Nanostructure of High-Temperature Sm-Co-Fe-Cu-Zr Magnet with Abnormal Temperature Dependence of Coercivity.
This paper presents methods and approaches that can be used for production of Sm-Co-Fe-Cu-Zr permanent magnets with working temperatures of up to 550 °C. It is shown that the content of Sm, Cu, and Fe significantly affects the coercivity (Hc) value at high operating temperatures. A decrease in the content of Fe, which replaces Co, and an increase in the content of Sm in Sm-Co-Fe-Cu-Zr alloys lead to a decrease in Hc value at room temperature, but significantly increase Hc at temperatures of about 500 °C. Increasing the Cu concentration enhances the Hc values at all operating temperatures. From analysis of the dependence of temperature coefficients of the coercivity on the concentrations of various constituent elements in this alloy, the optimum chemical composition that qualifies for high-temperature permanent magnet (HTPM) application were determined. 3D atom probe tomography analysis shows that the nanostructure of the HTPM is characterized by the formation of Sm2(Co,Fe)17 (2:17) cells relatively smaller in size along with the slightly thickened Sm(Co,Cu)5 (1:5) boundary phase compared to those of the high-energy permanent magnet compositions. An inhomogeneous distribution of Cu was also noticed in the 1:5 phase. At the boundary between 1:5 and 2:17 phases, an interface with lowered anisotropy constants has developed, which could be the reason for the observed high coercivity values.


In silico studies of the properties of water hydrating a small protein.
Atomistic molecular dynamics simulation of an aqueous solution of the small protein HP-36 has been carried out with explicit solvent at room temperature. Efforts have been made to explore the influence of the protein on the relative packing and ordering of water molecules around its secondary structures, namely, three α-helices. The calculations reveal that the inhomogeneous water ordering and density distributions around the helices are correlated with their relative hydrophobicity. Importantly, we have identified the existence of a narrow relatively dehydrated region containing randomly organized "quasi-free" water molecules beyond the first layer of "bound" waters at the protein surface. These water molecules with relatively weaker binding energies form the transition state separating the "bound" and "free" water molecules at the interface. Further, increased contribution of solid-like caging motions of water molecules around the protein is found to be responsible for reduced fluidity of the hydration layer. Interestingly, we notice that the hydration layer of helix-3 is more fluidic with relatively higher entropy as compared to the hydration layers of the other two helical segments. Such characteristics of helix-3 hydration layer correlate well with the activity of HP-36, as helix-3 contains the active site of the protein.


[Oxalis inhibits prostate tumor in the mouse model of castration-resistant prostate cancer: Effect and mechanism].
To investigate the inhibitory effect of oxalis on prostate tumor in the mouse model of castration-resistant prostate cancer (CRPC) and its action mechanism. We established a CRPC model in 40 male C57/BL mice aged 6-8 weeks, divided them randomly into four groups of an equal number, and treated them intragastrically with normal saline (control), low-dose oxalis (5 mg/kg/d), medium-dose oxalis (10 mg/kg/d), and high-dose oxalis (15 mg/kg/d), respectively. After 28 days of treatment, we measured the tumor volume and body weight of the mice in different groups, calculated the tumor-inhibition rate, examined the histomorphological changes of the prostate tumors by HE staining, and detected the expressions of the nuclear factor-κB (NF-κB) signaling pathway and its downstream proteins in the tumor tissue by immunofluorescence assay. In comparison with the controls, the mice in the low-, medium- and high-dose oxalis groups showed a gradual decrease in tumor cell concentration and cell degeneration, and a gradually increased number of necrotic tumor cells. The volume and mean weight of prostate tumors were significantly reduced (P < 0.05), the expressions of NF-κB p65 and Ki67 proteins remarkably down-regulated (P < 0.05), and that of the Bax protein markedly up-regulated (P < 0.05) in the oxalis groups compared with the controls. Oxalis can inhibit the growth of prostate tumor in CRPC mice possibly by down-regulating the NF-κB signaling pathway and the expressions of p65 and Ki67 and up-regulating the expression of Bax, and thereby promoting the degeneration and necrosis of tumor cells.


A chloroplast cyclophilin functions in the assembly and maintenance of photosystem II in Arabidopsis thaliana.
Photosynthetic light reactions rely on the proper function of large protein complexes (including photosystems I and II) that reside in the thylakoid membrane. Although their composition, structure, and function are known, the repertoire of assembly and maintenance factors is still being determined. Here we show that an immunophilin of the cyclophilin type, CYP38, plays a critical role in the assembly and maintenance of photosystem II (PSII) supercomplexes (SCs) in Arabidopsis. Mutant plants with the CYP38 gene interrupted by T-DNA insertion showed stunted growth and were hypersensitive to high light. Leaf chlorophyll fluorescence analysis and thylakoid membrane composition indicated that cyp38 mutant plants had defects in PSII SCs. Sucrose supplementation enabled the rescue of the mutant phenotype under low-light conditions, but failed to mitigate hypersensitivity to high-light stress. Protein radiolabeling assays showed that, although individual thylakoid proteins were synthesized equally in mutant and wild type, the assembly of the PSII SC was impaired in the mutant. In addition, the D1 and D2 components of the mutant PSII had a short half-life under high-light stress. The results provide evidence that CYP38 is necessary for the assembly and stabilization of PSII.


Septin2 is modified by SUMOylation and required for chromosome congression in mouse oocytes.
In mitosis, centrosomes nucleate microtubules that capture the sister kinetochores of each chromosome to facilitate chromosome congression. In contrast, during meiosis chromosome congression on the acentrosomal spindle is driven primarily by movement of chromosomes along laterally associated microtubule bundles. Previous studies have indicated that septin2 is required for chromosome congression and cytokinesis in mitosis, we therefore asked whether perturbation of septin2 would impair chromosome congression and cytokinesis in meiosis. We have investigated its expression, localization and function during mouse oocyte meiotic maturation. Septin2 was modified by SUMO-1 and its levels remained constant from GVBD to metaphase II stages. Septin2 was localized along the entire spindle at metaphase and at the midbody in cytokinesis. Disruption of septins function with an inhibitor and siRNA caused failure of the metaphase I /anaphase I transition and chromosome misalignment but inhibition of septins after the metaphase I stage did not affect cytokinesis. BubR1, a core component of the spindle checkpoint, was labeled on misaligned chromosomes and on chromosomes aligned at the metaphase plate in inhibitor-treated oocytes that were arrested in prometaphase I/metaphase I, suggesting activation of the spindle assembly checkpoint. Taken together, our results demonstrate that septin2 plays an important role in chromosome congression and meiotic cell cycle progression but not cytokinesis in mouse oocytes.


Acute purulent diverticulitis in the cecum: case report.
A 40-year-old female with a 24-hour course of abdominal pain suggestive of acute appendicitis. An emergency laparotomy was performed, finding plastron in the cecum and ascending colon, color changes, with purulent liquid and 5 cm in diameter, fixed to Toldt's. It was decided to perform a right hemicolectomy with an ileotransverse end-to-side anastomosis with adequate postsurgical evolution. The histopathological report showed acute purulent diverticulitis of the cecum, which is very low incidence in the Mexican population, that's why this case report is carried out.


Nanoscale Horizons Emerging Investigator Series: Dr Ahu Gümrah Dumanli-Parry, University of Manchester, UK.
Our Emerging Investigator Series features exceptional work by early-career nanoscience and nanotechnology researchers. Read Ahu Gümrah Dumanli-Parry's Emerging Investigator Series article 'Edible cellulose-based colorimetric timer' (https://doi.org/10.1039/D3NH00006K) and read more about her in the interview below.