Determinants of undernutrition and overnutrition among reproductive-age women in Bangladesh: Trend analysis using spatial modeling.
Bangladesh is facing a dual burden of malnutrition, with high rates of undernutrition and increasing rates of overnutrition. The complex scenario of malnutrition in Bangladesh varies across different regions, making it a challenging public health concern to address. This study analyzes the spatial and temporal dependence of underweight and overweight Bangladeshi women of reproductive age. Nationally representative cross-sectional data from the Bangladesh Demographic and Health Surveys in 2014 and 2017-18 were utilized to study the changes in weight status in 15-49-year-old women who were either underweight or overweight. A Bayesian geo-additive regression model was used to account for non-linear and linear effects of continuous and categorical covariates and to incorporate spatial effects of geographical divisions. The prevalence of overweight or obese women in rural, city corporations, and other urban areas increased significantly over the four years from 2014 to 2017-18. Women in the categories 'richer' and 'richest' were more likely to be overweight or obese. Women from Sylhet were more likely to be underweight in both survey years; however, the spatial effects were significant for underweight women in Mymensingh for the year 2017-18. Women in Rajshahi and Khulna were more likely to be overweight or obese in 2014, and women from Barishal and Chittagong were more likely to be overweight in the year 2017-18. Underweight and overweight statuses in women vary unevenly across Bangladesh, with a substantially higher prevalence of overweight or obese women in more urbanized areas. The growing burden of overweight and obesity among Bangladeshi women should be addressed with interventions aimed at those in the reproductive age group.


Acute, simultaneous tear of patellar tendon and ACL: possible mechanism of injury and rationality of the two-stage surgical treatment.
The authors report a case of a 47-year-old professional driver with an acute, simultaneous tear of patellar tendon and anterior cruciate ligament (ACL). The patient was treated in two stages. Acute patellar tendon repair and delayed (6-month postinjury) ACL reconstruction was performed. The authors discuss the possible mechanism of injury and the rationality of the two-stage surgical treatment.


Radiosensitization by derivatives of isoindole-4,7-dione.
New derivatives of isoindole -4,7-dione have been synthesized and their radiation sensitization and chemical behavior have been studied. One-electron reduction potentials have been determined by pulse radiolysis and found to be in the range of -0.45 to -0.36 V vs NHE . Radiosensitization effects were tested in vivo using soft tissue sarcoma transplanted in mice. All the isoindole -4,7-diones tested were found to exert considerable radiosensitization, approaching that of misonidazole tested under comparable conditions. The derivatives which contain a carbethoxy group on the pyrrolic ring were found to have more positive reduction potentials and to act as more efficient sensitizers. Further development of this class of radiosensitizers is underway.


In situ resuspension rate monitoring method in the littoral zone with multi-ecotypes of a shallow wind-disturbed lake.
Sediment resuspension has been recognized as a crucial internal process in aquatic ecosystems. However, there is still a lack of reliable measuring methods due to the complex hydrodynamic conditions in large shallow eutrophic lakes. In this study, sequential sediment traps (SST) and instantaneous multiple point (IMP) methods were compared at 6 sites located in the littoral zone of Zhushan Bay in Lake Taihu. Results show that the average resuspension rates (RRs) estimated using the IMP method at sites 1 to 6 were 266.39, 272.79, 235.17, 254.95, 392.25, and 483.85 g·m-2d-1, respectively. While the RRs estimated using the SST method were 195.16, 236.99, 116.76, 156.23, 389.53, and 509.85 g·m-2d-1, respectively. In wind-disturbed areas, both methods were suitable for RR analysis in large and shallow eutrophic lakes and SST provides high-resolution temporal RR estimations. However, in the areas with cyanobacterial blooms and vegetation cover, the IMP method overestimated the RR. Therefore, SST was more suitable across different conditions in large and shallow eutrophic lakes, providing a simple, accurate, and high-resolution temporal estimation of RR, while furthering our understanding of lake evolution processes.


Albuterol delivery via tracheostomy tube.
Albuterol delivery through a tracheostomy tube is affected by device (nebulizer vs metered-dose inhaler), interface (mask vs T-piece), bias flow, and humidification. A lift bar was placed between the chambers of a dual-chambered lung model such that a ventilator triggered simulated spontaneous breathing at a rate of 20 breaths/min, tidal volume of 0.4 L, and inspiratory-expiratory ratio of 1:2. An 8-mm inner diameter cuffed tracheostomy tube was placed through a semi-circular model that simulated a patient's neck. Four conditions of gas flow and humidification were used for the nebulizer experiments: heated aerosol (approximately 30 L/min, approximately 30 degrees C), heated humidity (approximately 30 L/min, approximately 30 degrees C), high flow without added humidity (approximately 30 L/min), or a nebulizer attached to the tracheostomy tube without additional flow. The nebulizer was filled with 4 mL that contained 2.5 mg of albuterol, and operated at 8 L/min. The nebulizer was tested with a T-piece or tracheostomy mask. For the metered-dose inhaler experiments, a spacer was used and actuation of the inhaler (100 microg per actuation) was synchronized with inhalation (4 actuations separated by > or = 15 s). When the spacer was used without additional flow, a valved T-piece was used with a 1-way valve placed either proximal or distal to the spacer. A filter was attached between the lung model and the distal end of the tracheostomy tube. Albuterol washed from the filter was measured by ultraviolet spectrophotometry. For the nebulizer, the most efficient delivery was with no flow other than that to power the nebulizer and with a T-piece (p < 0.001). The most efficient method for aerosol delivery was metered-dose inhaler with a valved T-piece and placement of the 1-way valve in the proximal position (p < 0.001). The effect of humidity was unclear from the results of this study. Albuterol delivery via tracheostomy was affected by the delivery device (nebulizer vs inhaler), bias gas flow, and the patient interface.


The redundant nerve root syndrome of the Cauda equina.
The redundant nerve root syndrome is defined as the association of high-grade extradural lumbar spinal stenosis with large, elongated and tortuous nerve roots. Acquired elongation of nerve roots due to the mechanical trapping at the level of lumbar spinal stenosis is assumed to be the possible mechanism. It is believed that the cause is a squeezing force due to the chronic compression. The most common clinical symptoms are low back pain and leg pain. Although lumbar spinal canal stenosis is common, the entity has rarely been discussed in the literature. Here we present the MR imaging and intraoperative appearance of the condition with a brief discussion in a 71-year-old woman.


Allogeneic bone marrow transplantation in leukemia.
This paper describes European experience of bone marrow transplantation for hematological malignancies. From 1979 until December 1986 2224 transplants were reported to the European registry. The results clearly show that the leukemia-free survival is highest when the transplant is performed in the first complete remission of acute leukemia or in the first chronic phase of chronic myeloid leukemia. Under these conditions 50% of the patients can be expected to be alive and well at 8 years after the transplantation. Other factors influencing leukemia-free survival are age, donor-recipient sex combination, and prevention of graft-versus-host disease with cyclosporine.


Unsedated flexible upper gastrointestinal endoscopy: need for routine oxygen monitoring?
To determine the incidence of oxygen desaturation and whether routine oxygen monitoring is necessary during unsedated diagnostic flexible upper gastrointestinalendoscopy. A prospective study involving 54 consecutive in and out patients who had diagnostic upper gastrointestinal endoscopy at the endoscopy suit of the Jos University Teaching Hospital, Jos, Nigeria between March 2007 and October 2007. The patients were reviewed before the procedure and classified according to the American Society of Anesthesiologists' (ASA) classification into classes I, II, III and IV Endoscopy was carried out after topical pharyngeal anaesthesia using 10% lidocaine spray and oxygen saturation was monitored throughout the procedure. There were 30 males and 24 females, with a male, female ratio of 1.25:1. The mean age was 46.7 with a range of 17 to 81 years. Mild to moderate desaturation occurred in 10 (18.5%) of the patients while severe desaturation occurred in 7 (12.9%) of the patients. All cases of severe desaturation lasted less than 30 seconds and no supplementary oxygen was needed. There were no significant statistical correlations between desaturation and gender, age, duration of procedure or ASA status of the patients. Routine oxygen monitoring may not be necessary in patients undergoing unsedated diagnostic upper gastrointestinal endoscopy and who do not have respiratory disease.


Xanthogranulomatous pyelonephritis: a retrospective review of 16 cases.
Xanthogranulomatous pyelonephritis is an uncommon disorder of unknown etiology that is characterized by extensive destruction of the involved kidney. It is being increasingly recognized as an important cause of renal morbidity around the world. This retrospective study was undertaken to review the xanthogranulomatous pyelonephritis cases presented at our tertiary care referral center in Bangalore, India. A total of 16 biopsy-proven cases of xanthogranulomatous pyelonephritis from October 2007 to March 2010 treated at our institute were included in the study. There were 10 females and 6 males with a mean age of 51.5 years. Flank pain was the most common presenting symptom followed by fever. All patients had unilateral disease and underwent total nephrectomy of the affected nonfunctional kidney. Xanthogranulomatous pyelonephritis is a chronic and unusual infectious inflammatory condition involving the renal parenchyma. The definite treatment is nephrectomy. Early identification and prompt treatment of this relatively benign and uncommon condition is important to minimize morbidity and mortality.


Evaluation of the usefulness of COVID-19 antigen tests in primary health care on the example of Kashubian Medical Centre in Sierakowice.
The SARS-CoV-2 pandemic is described as a global health crisis. The most typical symptoms of infection prompt most patients to visit a primary care clinic (PCC). From December 2020, COVID-19 can be diagnosed in European Union countries on the basis of a positive antigen test result. These tests are widely used at the primary care level. The analysis covered the period from 01.09.2021 to 28.02.2022. Statistical analysis was performed on the results of a study of 1,849 patients who underwent antigen testing in primary care clinics at the Kashubian Medical Centre (KCM) in Sierakowice and data published by the Ministry of Health on the results of tests performed from the whole country, Pomeranian Voivodeship and Kartuzy County. Statistical analysis showed that the results of studies conducted in KCM in Sierakowice (antigen-only tests) were consistent with the results of studies conducted in Kartuzy County, Pomeranian Voivodeship and nationwide (molecular PCR - Polymerase Chain Reaction and antigen tests). Rapid antigen tests are a useful diagnostic tool in the fight against the SARS-CoV-2 pandemic because of their easy availability and simplicity of performance, and their widespread dissemination, especially in primary care settings, could contribute to multibillion-dollar savings in the health care system.


Arylamidrazones as novel corticotropin releasing factor receptor antagonists.
The arylamidrazones have been found to be potent corticotropin releasing factor (CRF) receptor antagonists structurally distinct from previously reported CRF1 antagonists. Attempts to modify the arylamidrazone core suggested an important role for the anilino NH moiety. The right-hand-side 2-nitro feature in lead 1 could be replaced with substituents methyl, chloro, cyano, or trifluoromethyl with a 4- to 10-fold reduction in receptor binding. With appropriate left-hand-side modifications, this potency loss could be recovered.


Postgraduate education in healthy and active ageing: learning needs, curriculum and expected outcomes: a scoping review protocol.
Background: As the European population ages, it becomes increasingly important to promote and facilitate healthy and active ageing and age-friendly societies. Professionals across a range of disciplines and sectors need knowledge and skills to support both. Objective: This scoping review aims to identify and map the literature on learning needs, learning outcomes and respective curricula in healthy and active ageing and age-friendly society concepts. Inclusion criteria: Studies focused on the teaching/learning process in healthy and active ageing and/or age-friendly society, of any design type, are eligible. Included studies may focus on undergraduate, postgraduate or continuing education and on any aspect of the educational process, such as needs analysis, content delivery, learner satisfaction/acceptability, or education outcome. Methods: This review will follow the Joanna Briggs Institute (JBI) methodology for conducting scoping reviews. Four electronic databases, PubMed, EBSCO (Academic Search Complete), Scopus and Applied Social Sciences Index and Abstracts (ASSIA), will be searched, limited to studies published from 1 st January 2000. Text language will be limited to English, German, Greek, Portuguese, Finnish, and Slovenian. Google Scholar and Research Gate will be searched for grey literature, limited to the first 50 results of each. Title and abstract screening, followed by full-text screening will be undertaken independently by at least two reviewers. The JBI extraction tool will be adapted for data extraction. Quality assessment will be conducted using a tool developed by Hawker and colleagues. A narrative synthesis will outline the data in relation to the aims and objectives outlined.


Inhibition of UDP-glucuronosyltransferases by different furoquinoline alkaloids.
Herbs are often administered in combination with therapeutic drugs, raising the possibility for herb-drug interactions (HDIs). Furoquinoline alkaloids are found in Rutaceae plants, which are structurally similar and have many medicinal properties. This study aims to investigate the inhibition of four furoquinoline alkaloids on the activity of UDP-glucuronosyltransferases (UGTs).The recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition type and parameters were determined, and in silico docking was employed to elucidate the inhibition difference of furoquinoline alkaloids towards UGTs.Dictamine, haplopine, γ-fagarine and skimmianine strongly inhibited UGT1A3, UGT1A7, UGT1A9 and UGT2B4, respectively. Among them, dictamnine inhibited more than 70% of the four UGTs. Inhibition kinetics determination showed that they all exerted competitive inhibition, and the inhibition kinetic constant (Ki) was determined to be 8.3, 7.2, 3.7 and 33.9 μM, respectively. In vitro-in vivo extrapolation (IVIVE) was employed to demonstrate the inhibition possibility for four alkaloids. Skimmianine was proved to be more suitable for clinical application. In silico docking study indicated that the hydrophobic interactions played a key role in the inhibition of furoquinoline alkaloids towards three of the four UGTs. In conclusion, monitoring the interactions between furoquinoline alkaloids and drugs mainly undergoing UGTs-catalyzed metabolism is necessary.


Receptor-mediated endocytosis of alpha 2-macroglobulin in cultured fibroblasts.
Alpha 2-macroglobulin is internalized into cultured fibroblasts by receptor-mediated endocytosis. This ligand binds initially to diffusely distributed receptors on the cell surface which cluster rapidly into bristle-coated pits. Within a few minutes at 37 degrees C, these complexes are internalized into uncoated cytoplasmic vesicles, called receptosomes, which move about in the cell by saltatory motion. These vesicles interact with the Golgi-endoplasmic reticulum-lysosome system in the cell to deliver the ligand to newly formed lysosomes within 30--60 min.


[Relative growth of physiques in laboratory-bred cynomolgus monkeys: a longitudinal study during the first 6 years of life].
Physical growth was studied longitudinally in laboratory-bred cynomolgus monkeys (Macaca fascicularis) aged from birth to 6.0 years in females and to 6.5 years in males. An allometric formula was applied to morphometrical growth data and the relative growth of each morphological site to anterior trunk length was analyzed. The growth patterns of all of the measurement sites in females and most of the sites in males showed monophasic allometry; while those of head length, head breadth and morphological upper face length in males were judged to show diphasic allometry. The growth patterns of morphological total face length, upper arm length and lower arm length in some males showed diphasic allometry. Morphological measurements with negative allometry were head length, head breadth, morphological total face length, total head height, biacrominal breadth hand length and foot length, while the other morphological measurements revealed isometry in both sexes. However, the values of the relative growth coefficient to anterior trunk length were larger in males than in females, except for in the case of biiliac breadth. These differences in growth patterns may cause the morphological differences between genders after sexual maturation in this primate species.


Preoperative and operative predictive variables of late clinical events following saphenous vein coronary artery bypass graft surgery.
Prediction of late clinical events was studied in a series of 145 patients who had control angiographic studies at one year and between two and 14 years after saphenous vein coronary artery bypass graft surgery. During a mean observation interval of 7.4 years, new narrowing or occlusion occurred in grafts of 59% of the patients and progression in non-bypassed arteries was observed in 66%. One or several of the following events were observed in 56% of the patients: recurrent or worse effort angina, unstable angina, myocardial infarction and heart failure. Unstable angina during follow-up was more frequent in young patients and in those who had this clinical presentation before surgery. The incidence of myocardial infarction was likewise greater in patients who had preoperative unstable angina and in those with four to five risk factors for coronary artery disease, as well as those having a lesser number of inserted grafts. Heart failure was predicted independently by either four to five risk factors, a low left ventricular contraction score or fewer grafts placed at surgery. The number of inserted grafts correlated inversely with any one of the late clinical events.


Mesoscale model parameters from molecular cluster calculations.
We present an efficient, systematic, and universal method to estimate the interaction parameters used in mesoscale simulation methods such as dissipative particle dynamics and self-consistent field methods from molecular cluster calculations. The method is based on a generalized Flory-Huggins model in which molecules, or fragments thereof, are in contact with their van der Waals surface. We sample the density of states of molecular clusters in the space spanned by the coarse-grained degrees of freedom. From here, we calculate the sum over states and free energy of the cluster at a temperature of interest by histogram reweighting. The method allows to calculate the energy and entropy contributions to the cluster free energy explicitly. For two components, we then obtain the excess free energy of mixing and the Flory-Huggins chi-parameter, and their energetic and entropic contributions. We present two applications of the method: a simple liquid mixture of hexane and nitrobenzene, and a series of polymer blends. In the case of hexane/nitrobenzene, we compare to alternative simulation methods; here we find that the energy of mixing alone is too high to explain the critical point. By including the excess entropy of mixing, however, the predicted phase behavior is in reasonable agreement with experiment. The tendency of calculations based on average energy alone to overestimate the chi-parameter is also apparent in the polymer blend calculations.


Set-up of a high-resolution 300 mK atomic force microscope in an ultra-high vacuum compatible (3)He/10 T cryostat.
The design of an atomic force microscope with an all-fiber interferometric detection scheme capable of atomic resolution at about 500 mK is presented. The microscope body is connected to a small pumped (3)He reservoir with a base temperature of about 300 mK. The bakeable insert with the cooling stage can be moved from its measurement position inside the bore of a superconducting 10 T magnet into an ultra-high vacuum chamber, where the tip and sample can be exchanged in situ. Moreover, single atoms or molecules can be evaporated onto a cold substrate located inside the microscope. Two side chambers are equipped with standard surface preparation and surface analysis tools. The performance of the microscope at low temperatures is demonstrated by resolving single Co atoms on Mn/W(110) and by showing atomic resolution on NaCl(001).


Generative organic electronic molecular design informed by quantum chemistry.
Generative molecular design strategies have emerged as promising alternatives to trial-and-error approaches for exploring and optimizing within large chemical spaces. To date, generative models with reinforcement learning approaches have frequently used low-cost methods to evaluate the quality of the generated molecules, enabling many loops through the generative model. However, for functional molecular materials tasks, such low-cost methods are either not available or would require the generation of large amounts of training data to train surrogate machine learning models. In this work, we develop a framework that connects the REINVENT reinforcement learning framework with excited state quantum chemistry calculations to discover molecules with specified molecular excited state energy levels, specifically molecules with excited state landscapes that would serve as promising singlet fission or triplet-triplet annihilation materials. We employ a two-step curriculum strategy to first find a set of diverse promising molecules, then demonstrate the framework's ability to exploit a more focused chemical space with anthracene derivatives. Under this protocol, we show that the framework can find desired molecules and improve Pareto fronts for targeted properties versus synthesizability. Moreover, we are able to find several different design principles used by chemists for the design of singlet fission and triplet-triplet annihilation molecules.


CPR for your AR.
Physicians' practices constantly seek to improve their cash flow by better managing their accounts receivable. While one "best" method to make this happen does not exist, practices ofall types and sizes can adopt a number of simple and sensible procedures to help maximize collections--and the earlier a practice begins the collection process, the higher the probability of optimizing the results. Creating easy-to-understand goals, involving the right teams, demonstrating progress, and fostering a culture of accountability are but a few ofthe ways practices can begin working toward the goal of a more positive cash flow for the practice.


Asthma: addressing consistency in results from basic science, clinical trials, and observational experience.
The basic science understanding of the pathophysiology of a disease often serves as the basis for clinical investigations. This knowledge is used to propose new directions in care and confirm initial concepts. The basic science of asthma demonstrates that the most comprehensive management of inflammation appears to be associated with the use of inhaled corticosteroids and proposes a mechanism for combination therapy with the addition of salmeterol. Randomized clinical trials are performed to confirm these initial observations and demonstrate both the safety and efficacy of therapeutic agents. These investigations are either placebo-controlled or direct comparisons of 2 medications. For the treatment of asthma, these studies have all consistently demonstrated that inhaled corticosteroids are the most effective primary controller therapy. Greater improvement in both lung function and patient-oriented symptom control is observed with the use of inhaled corticosteroids. For patients whose symptoms are not controlled with single-drug therapy, the addition of a long-acting bronchodilator appears to be the most effective add-on treatment with the greatest improvement in lung function and symptom control. Clinical trials have been used for the purposes of cost modeling. Therapies that produce the greatest effect size at the lowest incremental costs produce the greatest improvement in cost-effectiveness. Retrospective claims analysis, more recently, have been used to validate these observations from clinical trials. These studies measure both resource use and costs or charges. These analyses have confirmed that initial treatment with inhaled corticosteroids and combined treatment with inhaled corticosteroids and long-acting bronchodilators are the most effective stepwise approaches to the treatment of asthma.


Novel benzene ring biosynthesis from C(3) and C(4) primary metabolites by two enzymes.
The shikimate pathway, including seven enzymatic steps for production of chorismate via shikimate from phosphoenolpyruvate and erythrose-4-phosphate, is common in various organisms for the biosynthesis of not only aromatic amino acids but also most biogenic benzene derivatives. 3-Amino-4-hydroxybenzoic acid (3,4-AHBA) is a benzene derivative serving as a precursor for several secondary metabolites produced by Streptomyces, including grixazone produced by Streptomyces griseus. Our study on the biosynthesis pathway of grixazone led to identification of the biosynthesis pathway of 3,4-AHBA from two primary metabolites. Two genes, griI and griH, within the grixazone biosynthesis gene cluster were found to be responsible for the biosynthesis of 3,4-AHBA; the two genes conferred the in vivo production of 3,4-AHBA even on Escherichia coli. In vitro analysis showed that GriI catalyzed aldol condensation between two primary metabolites, l-aspartate-4-semialdehyde and dihydroxyacetone phosphate, to form a 7-carbon product, 2-amino-4,5-dihydroxy-6-one-heptanoic acid-7-phosphate, which was subsequently converted to 3,4-AHBA by GriH. The latter reaction required Mn(2+) ion but not any cofactors involved in reduction or oxidation. This pathway is independent of the shikimate pathway, representing a novel, simple enzyme system responsible for the synthesis of a benzene ring from the C(3) and C(4) primary metabolites.


Successful Use of Tofacitinib in Scleroderma Arthropathy.
Musculoskeletal manifestations of systemic sclerosis (SSc) are frequent and may be one of the early manifestations of the disease. However, arthralgia, pain and stiffness without frank arthritis usually constitute the clinical picture, while overlap syndromes such as rheumatoid-like polyarthritis can dominate when the arthritis is erosive. Hereby, we report a case of primary SSc presenting as frank erosive arthritis involving small and large joints mimicking rheumatoid arthritis, unresponsive to methotrexate, which was successfully treated with tofacitinib.


Perceived discrimination, social support, and psychological distress in transgender individuals.
The present study aimed to find the relationship among perceived discrimination, social support, and psychological distress in transgender individuals (TIs) and the predictors of psychological distress in TIs. A correlational research design was used in the present study. It was hypothesized that there would likely to be a positive relationship between perceived discrimination and psychological distress and that there would likely be a negative relationship between social support and psychological distress. It was also hypothesized that perceived discrimination would predict psychological distress. Permission for using the questionnaires was taken from the authors of the original tools and the authors of the Urdu translated versions of the tools. The sample of 111 participants with an age range of 20-65 years was recruited by using purposive and non-probability snowball sampling techniques. The Everyday Perceived Discrimination Scale, the Multidimensional Scale of Perceived Social Support, and the Kessler Psychological Distress Scale were used to determine perceived discrimination, social support, and psychological distress, respectively, in TIs. Results revealed that there was a significant positive relationship between perceived discrimination and psychological distress, a significant negative relationship between social support and psychological distress, and there was also a significant negative relationship between perceived discrimination and social support. Additional findings revealed that perceived discrimination was found more in younger TIs than older TIs while social support from significant others was greater for younger TIs than for their older counterparts.


Two-dimensional gel analysis of Sertoli cell protein phosphorylation: effect of short term exposure to follicle-stimulating hormone.
The response of cultured Sertoli cells to short term FSH stimulation was studied to elucidate early events involved in the hormone response of this cell type. The phosphorylation of proteins by [32P]orthophosphate-labeled cells was examined using two-dimensional polyacrylamide gel electrophoresis and autoradiography. FSH stimulation resulted in a variety of changes in the phosphoprotein labeling pattern. Within 5 min, unique phosphoproteins appeared in autoradiograms of treated cells. Increased labeling of vimentin was also noted. After 25 min of FSH stimulation, increases and decreases in apparent labeling intensity were evident in additional phosphoproteins that were constitutively labeled in control cultures. Changes in protein patterns in stained gels were also noted after acute hormone treatment. These observations demonstrate that Sertoli cells respond to hormonal stimulation in a detectable manner within 5 min. Cytoskeletal involvement in initial phases of hormone response is indicated. Mechanisms such as increased protein kinase activity, changes in protein kinase substrate affinity, increased protein turnover, or phosphatase activation may all contribute to the early events involved in Sertoli cell hormone response.


Evolution of nutritional therapy prescription in critically ill patients.
The aim of this study was to investigate factors that may affect the evolution of the caloric prescription in critically ill patients. Local: Intensive care unit patients. 60 patients (33 M and 27 F); median age = 49 (1593) y were followed prospectively. They were divided in three groups according to the diagnostic: (a) trauma (n=20); (b) surgical (n=22), and 3) medical treatment (n=18). Forty-and-one (68.3%) patients received enteral nutrition (EN), 17 (28.3%) parenteral nutrition (TPN), and 2 (3.4%) TNP and EN. Nutritional status was graded B or C by global subjective evaluation. Endpoints of the study were the time to begin the nutritional support, success or failure of the caloric prescription, and the evolution of the planned caloric prescription. The caloric evolution was considered as success if the prescription for the patient attained: (a) 25% of the caloric requirements on the 1st day; (b) 50% until the 3rd day; (c) 75% until the 6th day; and (e) 100% until the 10th day of the beginning of the support. In 54 (90%) patients, the nutritional support has begun until 48 h after admission and in 73.3% (44 patients), until the first 24 hours. EN was most prescribed for both trauma and medical patients while NPT was most used for surgical patients (p < 0.01). Success in caloric prescription was obtained in 73.3% (44) of the patients. There was no statistical difference for the success on the evolution of the prescription related to sex, age, diagnostic group, albumin level, type of support, mortality, use of fiber or glutamine. Success was attained earlier in patients without (median = 3.8 [95% CI, 5.7-16.7] days) than with (11.2 [95% CI, 5.7-16.7] days; p < 0.01) mechanical ventilation. Early nutritional support and success on the evolution of the caloric prescription can be accomplished in most critically ill patients. Evolution of the caloric prescription was slower in mechanical ventilated patients.


A top-down approach for fabricating three-dimensional closed hollow nanostructures with permeable thin metal walls.
We report on a top-down method for the controlled fabrication of three-dimensional (3D), closed, thin-shelled, hollow nanostructures (nanocages) on planar supports. The presented approach is based on conventional microelectronic fabrication processes and exploits the permeability of thin metal films to hollow-out polymer-filled metal nanocages through an oxygen-plasma process. The technique is used for fabricating arrays of cylindrical nanocages made of thin Al shells on silicon substrates. This hollow metal configuration features optical resonance as revealed by spectral reflectance measurements and numerical simulations. The fabricated nanocages were demonstrated as a refractometric sensor with a measured bulk sensitivity of 327 nm/refractive index unit (RIU). The pattern design flexibility and controllability offered by top-down nanofabrication techniques opens the door to the possibility of massive integration of these hollow 3D nano-objects on a chip for applications such as nanocontainers, nanoreactors, nanofluidics, nano-biosensors and photonic devices.


Investigation of tissue thermal damage process with application of direct sensitivity method.
In the paper the numerical analysis of thermal processes proceeding in the biological tissue is presented. The tissue is subjected to the external heat flux and 2D problem is taken into account. In order to determine the influence of variations of thermophysical parameters of tissue on the value of Arrhenius injury integral the direct approach of sensitivity analysis is applied. On the basis of tissue damage fraction the thermal injury formation process is analysed. At the stage of numerical realization the boundary element method is used. In the final part of the paper the example of numerical simulation is shown.


Muscle-tendon mechanics explain unexpected effects of exoskeleton assistance on metabolic rate during walking.
The goal of this study was to gain insight into how ankle exoskeletons affect the behavior of the plantarflexor muscles during walking. Using data from previous experiments, we performed electromyography-driven simulations of musculoskeletal dynamics to explore how changes in exoskeleton assistance affected plantarflexor muscle-tendon mechanics, particularly for the soleus. We used a model of muscle energy consumption to estimate individual muscle metabolic rate. As average exoskeleton torque was increased, while no net exoskeleton work was provided, a reduction in tendon recoil led to an increase in positive mechanical work performed by the soleus muscle fibers. As net exoskeleton work was increased, both soleus muscle fiber force and positive mechanical work decreased. Trends in the sum of the metabolic rates of the simulated muscles correlated well with trends in experimentally observed whole-body metabolic rate (R2=0.9), providing confidence in our model estimates. Our simulation results suggest that different exoskeleton behaviors can alter the functioning of the muscles and tendons acting at the assisted joint. Furthermore, our results support the idea that the series tendon helps reduce positive work done by the muscle fibers by storing and returning energy elastically. We expect the results from this study to promote the use of electromyography-driven simulations to gain insight into the operation of muscle-tendon units and to guide the design and control of assistive devices.


Myoclonus in neuronal storage and Lafora diseases.
Genetic storage diseases with prominent myoclonus include classic infantile Tay-Sachs disease and juvenile neuropathic Gaucher's disease among the sphingolipidoses, most of the variants of the sialidoses and ceroid-lipofuscinoses, and Lafora disease. The character of the myoclonus differs from disease to disease and often changes as the disease runs its course. For example, massive myoclonic jerks to sound with rapid habituation and a prolonged refractory period are characteristic of the early stages of Tay-Sachs disease; children with late infantile ceroid-lipofuscinosis are most sensitive to light flashes below 3 Hz, those with juvenile Gaucher's disease at 6 to 10 Hz, and those with Lafora disease at 15 to 20 Hz, whereas young adults with sialidosis are not sensitive to either light or sound but are highly sensitive to somatosensory stimulation and movement. Some patients with sialidosis were found to have two distinct types of myoclonus: (a) a stimulus-insensitive facial myoclonus without EEG correlate that persisted in slow-wave sleep and (b) stimulus-sensitive massive jerks associated with vertex positive EEG spikes on which sleep had the paradoxic effect of suppressing jerks while stimulating spikes. Systematic EEG and event-related potential studies, including backward averaging from jerks and detailed anatomic studies of postmortem specimens with modern histochemical techniques, may help illuminate these intriguing differences. New modalities are needed to treat the myoclonus of these diseases since it generally responds poorly to currently available pharmacologic agents.


[A comparative study on long-term care facilities for the aged in Japan].
Presently in Japan, care for the aged who are bedridden, afflicted with dementia or other conditions, is provided by hospitals, skilled nursing homes (providing a certain amount of medical care) and special nursing homes (for those needing ADL assistance). Facilities for long term care of the aged are insufficient, and there are many problems in matching care needs to the services supplied in these facilities. In October 1990, a survey was conducted to collect data for helping define the optimum services needed for the aged in long term care facilities. The subjects consisted of 1,262 persons in 12 facilities: 314 in three general hospitals (average age: 78.5); 391 in three hospitals for the aged (80.8); 410 in four skilled nursing homes (81.2); 147 in two special nursing homes (81.3). Results of the survey are as follows: 1. The proportion of "seriously demented" and "very seriously demented" subjects, (according to Karasawa's scale.), was 17.5% in general hospitals, 28.7% in hospitals for the aged, 16.4% in skilled nursing homes, and 22.6% in special nursing homes. 2. For ADL, "mobility" with whole assistance was required for 40.5% of the subjects in general hospitals, 58.7% in hospitals for the aged, 22.9% in skilled nursing homes, and 37.5% in special nursing homes. 3. During the month preceding the survey, medical examinations were conducted on 98.4% in general hospitals, 99.5% in hospitals for the aged, 23.0% in skilled nursing homes, and 59.4% in special nursing homes. These examinations consisted mostly of urine and blood analyses. ECGs and x-ray tests were also performed on more than 70% of subjects in the two types of hospitals.


Adenotonsillar granuloma: histopathological correlation.
This study was undertaken to investigate the presence and nature of granulomatous changes in the adenotonsillar tissues and their relation to systemic disorders. The study was a retrospective clinicopathological review; 21,410 specimens of tonsil and adenoid tissue were subjected to histological examination during the period from 1995 to 2003. Twenty-three cases of tonsillar and adenoid granuloma (12 males and 11 females) were identified. Haemotoxylin and eosin stains were reviewed and clinical features noted. Of 23 cases, 11 were adenotonsillectomies, 10 tonsillectomies, 1 adenoidectomy and 1 excision biopsy of the right tonsil. Histologically, the slides reviewed showed 4 types of granulomatous inflammation that can affect the adenotonsillar tissues. The most common type was non-caseating epithelioid granulomas. Clinically, 22 cases presented with symptoms of chronic tonsillitis, nasal obstruction and obstructive sleep apnoea. None had any systemic granulomatous disorders. Only 1 case had tuberculosis. In all the cases but one there was no obvious systemic aetiology for the granulomatous changes in the adenotonsillar tissues. Hence, the cost effectiveness of clinicopathological examination of the resected adenoid and tonsil is still questionable.


Cytokines dynamics in a wistar rat model infected with Mycobacterium Tuberculosis strain H37Rv.
The immunology characteristics of the rat model of tuberculosis (TB) infection are still unclear. This study aimed to evaluate the dynamics of pathology and cytokines in a rat model infected with Mycobacterium TB (MTB). Sixty male Wistar rats were divided into four groups, namely the control group (without MTB infection) and the MTB -induced group (observations at week-3, week-6, and week-12 postinfection). Granuloma formation was analyzed by histology procedure. Analysis of the levels of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), IL-17, IL-2, IL-4, and IL-12 was performed using an enzyme-linked immunosorbent assay technique. The number and size of the ganulomas increased proportionally between weeks 6 and 12 postinfection. Several cytokines, namely IL-6, IL-17, IL-2, IL-4, and IL-12 significantly increased in the 6th week compared to the 3rd week after infection (P < 0.05). These cytokines decreased significantly at the 12th week compared to the 6th week (P < 0.05). TNF-α was found to be stable at the third and 6th weeks and then decreased at the twelfth postinfection week. For IL-12, the longer the infection time, the higher the level. It was concluded that there was a typical pattern of TB infection in Wistar rats, namely certain cytokines that peaked at week 6 of infection. Thus, TB infection in rats can be a model for early-phase TB study.


Microstructuration induced differences in the thermo-optical and luminescence properties of Nd:YAG fine grain ceramics and crystals.
The temperature and compositional dependences of thermo-optical properties of neodymium doped yttrium aluminum garnet (YAG) crystals and fine grain ceramics have been systematically investigated by means of time-resolved thermal lens spectrometry. We have found that Nd:YAG ceramics show a reduced thermal diffusivity compared to Nd:YAG single crystals in the complete temperature range investigated (80-300 K). The analysis of the time-resolved luminescent properties of Nd(3+) has revealed that the reduction in the phonon mean free path taking place in Nd:YAG ceramics cannot be associated with an increment in the density of lattice defects, indicating that phonon scattering at grain boundaries is the origin of the observed reduction in the thermal diffusivity of Nd:YAG ceramics. Finally, our results showed the ability of the time-resolved thermal lens to determine and optimize the thermo-optical properties of Nd:YAG ceramic based lasers.


Effectiveness of instituting a specific bed protocol in reducing complications associated with bed rest.
Pressure ulceration, deep venous thromboembolism, and hospital-acquired pneumonia are well-known complications of bed rest. This retrospective, single-center, observational cohort study evaluated the effectiveness of instituting bed rest protocol that included specific positioning, continuous heel off-loading, recumbent upper and lower body bed exercises, scheduled incentive spirometry, frequent position changes, and thromboprophylaxis (chemical, mechanical, or both), in reducing the incidence of pressure ulceration, deep venous thromboembolism, and hospital-acquired pneumonia in consecutive patients admitted for at least 7 days. A total of 29 patients (24 males, 5 females) were included in this study, with a mean age of 62.5 (median 63, range 17 to 84) years. The mean length of bed rest was 13.1 (median 10, range 7 to 31) days; and, the mean length of hospital stay was 21.1 (median 17, range 8 to 72) days. During hospitalization, 2 (6.9%) patients developed one or more of the complications measured, with 1 developing a posterior heel pressure ulcer that resolved with local care and another who developed deep venous thrombosis without pulmonary embolism, managed with therapeutic anticoagulation, and hospital-acquired pneumonia treated with antibiotic therapy. The results of this analysis were favorable in comparison with previously reported incidence rates for pressure ulcer, deep venous thrombosis, and hospital-acquired pulmonary complications in patients with similar risk factors, and suggested that a prescribed bed protocol reduces complications associated with bed rest.


Prognostic information from fine-needle aspiration biopsy of breast carcinoma.
Fine-needle aspiration of the breast is one of the most common procedures performed on patients with a palpable breast mass. The pathologist needs to be aware of the diagnostic and prognostic parameters that must be included in the cytopathology report of breast carcinomas. These fundamental parameters include tumor type, nuclear grade of the carcinoma, and hormone receptor status.


Phantom pain with probable reflex sympathetic dystrophy: efficacy of fentanyl infiltration of the stellate ganglion.
The stellate ganglion can alleviate phantom pain of the upper extremity, possibly because of the presence in it of enkephalin receptors, as has been suggested by experimental and clinical reports. A case is reported in which fentanyl, instead of local anesthetic, was used for stellate ganglion block. A 49-year-old man, with a left below-elbow amputation, presented with probable symptoms of reflex sympathetic dystrophy, pain and temperature changes at the stump, and phantom hand symptoms the English-language literature revealed no reports of the use of fentanyl infiltration of the stellate ganglion was performed for management of this condition. Significant alleviation of pain and sensation of warmth at the stump and in the phantom hand was achieved. Fentanyl infiltration of the stellate ganglion proved to be successful in the management of the pain and temperature sensation changes in the stump and phantom upper extremity.


Recent extraction techniques for natural products: microwave-assisted extraction and pressurised solvent extraction.
In the last 10 years there has been an increased interest in using techniques involving microwave-assisted extraction and pressurised solvent extraction in analytical laboratories. This review gives a brief overview of both methods, and reports on their application to the extraction of natural products. The influence of parameters such as the nature of the solvent and volume, temperature, time and particle size of the matrix is discussed. Through numerous examples, it is demonstrated that both techniques allow reduced solvent consumption and shorter extraction times, while the extraction yields of the analytes are equivalent to or even higher than those obtained with conventional methods.


Barriers and facilitators to preparing families with premature infants for discharge home from the neonatal unit. Perceptions of health care providers.
To explore Colombian health care provider perceptions of barriers and facilitators to preparing families with premature infants for discharge home from the neonatal intensive care unit (NICU). Using a qualitative descriptive design, in-depth semi-structured interviews were conducted with fifteen neonatal health care providers (HCPs) in Colombia. Data were analyzed using qualitative content analysis. Participant responses centered on three main themes: 1) establishment of the parent-infant bond, 2) acquisition of parenting skills, and 3) getting ready for the transition from hospital to home. Barreirs to preparing parents for NICU discharge included obstacles to parental visiting in the NICU, communication barriers, difficulties related to the establishment of successful breastfeeding, insufficient human resources and poor links between hospital and community-based resources. Facilitators included the availability of social aids for vulnerable families, 24-hour telephone access to the neonatal units, tailored educational materials and group sessions, continuing education for staff and the community-based Kangaroo Program available to parents post-discharge. Adolescent mothers, indigenous parent and working fathers were identified as particularly challenging to reach and engage in discharge preparation. Neonatal HCPs identified numerous challenges as well as helpful strategies for preparing families for hospital discharge. Additional studies are needed on the experience of neonatal discharge from the perspective of parents of premature infants in Colombia, to help inform optimal interventions for supporting families during the transition from hospital to home.


Sexual impotence: a complication of external sphincterotomy.
In paraplegic patients with upper motor neuron lesions, endoscopic sphincterotomy is a commonly used procedure to lower sphincter resistance and facilitate voiding. The technique yields 95% satisfactory clinical results. In the recent literature several authors report on temporary or permanent loss of erections after sphincterotomy. The 3 and 9 o'clock incision and resection appear to carry a higher risk (30-60%) than operations performed at the 1 and 11 o'clock or the 12 0'clock position (0-6%). Impairment of erectile reflex activity is more frequently observed in cases with severe intraoperative bleeding requiring deep coagulation and in the event of reoperation. We report on the clinical, radiological and urodynamic findings of a series of 47 cases (3 and 9o'clock resections). Partial and/or temporary inhibition of erection was observed in 5, total and permanent loss in 1 patients.=


Novel Stemness-Related Gene Signature Predicting Prognosis and Indicating a Different Immune Microenvironment in HNSCC.
Background: The head and neck squamous cell carcinomas (HNSCC) is one of the most frequent cancers in the world, with an unfavorable prognosis. Cancer stem cells (CSCs) have been found to be responsible for HNSCC recurrence and therapeutic resistance. Methods: The stemness of HNSCC was measured using a stemness index based on mRNA expression (mRNAsi). Stemness-related genes were discovered using weighted gene co-expression network analysis, least absolute shrinkage and selection operator analysis, and Cox regression, and a stemness-related prognostic index (SPI) was constructed. This research was based on TCGA and GSE65858. Results: Stemness was found upregulated in HNSCC compared with normal tissues. The risk score model including five stemness-related genes exhibited a good accuracy in predicting outcomes. High SPI predicted a shorter overall survival (OS) in HNSCC patients, in the meantime, also demonstrated a lower CD8+ T cell infiltration and a higher enrichment of macrophages and fibroblasts than the low-SPI group, focusing on several up-regulated pathways such as epithelial mesenchymal transition (EMT), MYC targets v1, E2F targets, mTORC1 signaling, hypoxia, MYC targets v2, angiogenesis, G2M checkpoint, and glycolysis. Conclusion: The SPI signature, which includes five stemness-related genes, could be utilized as a prognostic biomarker for HNSCC, implying that stemness may impact HNSCC immunologic profiles and be a feasible therapeutic target.


[Studies on release behavior of sustained release tablets of extracts of Gardenia by antioxidant activity].
Using sustained release tablets of gardenia extract as model drug and DPPH radical scavenging capacity as antioxidant index, the feasibility of using pharmacodynamics index was explored to evaluate sustained release tablets. Applying the established quantifiable method of DPPH radical scavenging to the dissolved liquid of model drug, release profiles and biological effects profiles were drawn, and their correlation was discussed. A good correlation was observed by linear regression and f2 actor, suggesting that the indicator could be used to evaluate sustained release tabletsofextracts of gardenia in which iridoids were mainly involved.


Second opinions from urologists for prostate cancer: Who gets them, why, and their link to treatment.
Cancer patients are encouraged to obtain second opinions before starting treatment. Little is known about men with localized prostate cancer who seek second opinions, the reasons why, and the association with treatment and quality of care. We surveyed men who were diagnosed with localized prostate cancer in the greater Philadelphia area from 2012 to 2014. Men were asked if they obtained a second opinion from a urologist, and the reasons why. We used multivariable logistic regression models to evaluate the relationship between second opinions and definitive prostate cancer treatment and perceived quality of care. A total of 2386 men responded to the survey (adjusted response rate, 51.1%). After applying exclusion criteria, the final analytic cohort included 2365 respondents. Of these, 40% obtained second opinions, most commonly because they wanted more information about their cancer (50.8%) and wanted to be seen by the best doctor (46.3%). Overall, obtaining second opinions was not associated with definitive treatment or perceived quality of cancer care. Men who sought second opinions because they were dissatisfied with their initial urologist were less likely to receive definitive treatment (odds ratio, 0.49; 95% confidence interval, 0.32-0.73), and men who wanted more information about treatment were less likely to report excellent quality of cancer care (odds ratio, 0.70; 95% confidence interval, 0.49-0.99) compared with men who did not receive a second opinion. Although a large proportion of men with localized prostate cancer obtained a second opinion, the reasons for doing so were not associated with treatment choice or perceived quality of cancer care. Future study is needed to determine when second opinions contribute to increasing the value of cancer care. Cancer 2017;123:1027-34. © 2016 American Cancer Society.


Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance.
Kidney‑type glutaminase (GLS1) plays a significant role in tumor metabolism. Our recent studies demonstrated that GLS1 was aberrantly expressed in hepatocellular carcinoma (HCC) and facilitated tumor progression. However, the roles of GLS1 in intrahepatic cholangiocarcinoma (ICC) remain largely unknown. Thus, the aim of this study was to evaluate the expression and clinical significance of GLS1 in ICC. For this purpose, combined data from the Oncomine database with those of immunohistochemistry were used to determine the expression levels of GLS1 in cancerous and non‑cancerous tissues. Second, a wound‑healing assay and Transwell assay were used to observe the effects of the knockdown and overexpression of GLS1 on the invasion and migration of ICC cells. We examined the associations between the expression of GLS1 and epithelial‑mesenchymal transition (EMT)‑related markers by western blot analysis. Finally, we examined the associations between GLS1 levels and clinicopathological factors or patient prognosis. The results revealed that GLS1 was overexpressed in different digestive system tumors, including ICC, and that GLS1 expression in ICC tissue was higher than that in peritumoral tissue. The overexpression of GLS1 in RBE cells induced metastasis and invasion. Moreover, the EMT‑related markers, E‑cadherin and Vimentin, were regulated by GLS1 in ICC cells. By contrast, the knockdown of GLS1 expression in QBC939 cells yielded opposite results. Clinically, a high expression of GLS1 in ICC samples negatively correlated with E‑cadherin expression and positively correlated with Vimentin expression. GLS1 protein expression was associated with tumor differentiation (P=0.001) and lymphatic metastasis (P=0.029). Importantly, patients with a high GLS1 expression had a poorer overall survival (OS) and a shorter time to recurrence than patients with a low GLS1 expression. Multivariate analysis indicated that GLS1 expression was an independent prognostic indicator. On the whole, the findings of this study demonstrated that GLS1 is an independent prognostic biomarker of ICC. GLS1 facilitates ICC progression and may thus prove to be a therapeutic target in ICC.


The influence of asphyxia on phenobarbital dosing requirements in neonates.
phenobarbital dosing requirements and plasma clearance were examined for asphyxiated and nonasphyxiated neonates. The gestational age, postnatal age, duration of phenobarbital therapy and plasma phenobarbital concentrations were similar for the two groups. The plasma phenobarbital clearance was 4.1 +/- 1.0 (SD) and 8.7 +/- 3.9 (SD) ml/kg/h for asphyxiated and nonasphyxiated neonates, respectively. Asphyxiated neonates only require about half the maintenance dose of nonasphyxiated neonates to achieve similar plasma concentrations.


Cognitive functions and the antioxidant system in phenylketonuric patients.
The authors studied the relationship between the antioxidant system and cognitive functions in a group of 36 early and continuously treated phenylketonuric (PKU) patients (mean age=9.7 years) and 29 controls. The authors measured antioxidant cofactors and free radical damage markers in plasma (selenium, retinol, tocopherol, coenzyme Q10, malondialdehide) and antioxidant enzymes in red blood cells (glutathione peroxidase, catalase, superoxide dismutase). The authors used neuropsychological tests to screen for several cognitive functions. PKU patients showed significantly lower values of selenium, coenzyme Q10, and catalase, and significantly higher levels of malondialdehide. PKU patients showed a significantly negative correlation between plasma selenium concentrations and several Conner's Continuous Performance Test measures (more omission errors, fluctuating attention and inconsistency of response times, and slowing reaction time as the test progressed). Selenium deficiency was thus associated with a worsened performance on the Conner's Continuous Performance Test among PKU patients. In conclusion, it is important not only to control blood Phe levels in PKU but also other nutritional components such as selenium. Selenium status seems to be associated with attention functions in these PKU patients.


Changes in Foot Skin Microbiome of Patients with Diabetes Mellitus Using High-Throughput 16S rRNA Gene Sequencing: A Case Control Study from a Single Center.
BACKGROUND Worldwide, the treatment of complications associated with type 2 diabetes mellitus, including diabetic foot ulcer (DFU), results in an economic burden for patients and healthcare systems. This study aimed to use high-throughput 16S rRNA gene sequencing to investigate the changes in foot skin microbiome of patients with diabetes mellitus from a single center in China. MATERIAL AND METHODS Fifty-two participants were divided into 4 study groups: healthy controls (n=13); patients with short-term diabetes (<2 years; n=13); patients with intermediate-term diabetes (5-8 years; n=13); and patients with long-term diabetes (>10 years; n=13). Swabs were analyzed from the intact skin of the foot arch using high-throughput 16S ribosomal RNA sequencing. RESULTS Microbiome phylogenic diversity varied significantly between the study groups (whole tree, P<0.01; Chao1, P<0.01), but were similar within the same group. The findings were supported by non-parametric multidimensional scaling (stress=0.12) and principal component analysis (principal component 1, 8.38%; principal component 2, 5.28%). In patients with diabetes mellitus, the dominant skin microbial phyla were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. CONCLUSIONS High-throughput 16S rRNA gene sequencing showed dynamic changes in the skin microbiome from the foot during the progression of diabetes mellitus. These findings support the importance of understanding the role of the skin microbiota in the pathogenesis of DFU.


Global control of pneumococcal infections by pneumococcal vaccines.
Streptococcus pneumoniae is a major worldwide cause of morbidity and mortality. Pneumococcal carriage is considered to be an important source of horizontal spread of this pathogen within the community. Pneumococcal conjugate vaccine (PCV) is capable of inducing serotype-specific antibodies in sera of infants, and has been suggested to reduce nasopharyngeal carriage of vaccine-type pneumococci in children. PCV is generally immunogenic for pediatric patients with invasive pneumococcal disease, with an exception for the infecting serotypes. Based on evidences from the clinical trials of PCV, the health impact of childhood pneumococcal pneumonia appears to be high in developing countries where most of global childhood pneumonia deaths occur. PCV vaccination may prevent hundreds of deaths per 100,000 children vaccinated in developing countries, while PCV vaccination is expected to prevent less than 10 deaths per 100,000 children vaccinated in the developed countries. Therefore, the WHO has proposed a strategy to reduce the incidence of severe pneumonia by 75% in child less than 5 years of age compared to 2010 levels by 2025.


Isolated right ventricular rupture: a rare complication of myocardial infarction.
Right ventricular rupture is a rare complication after myocardial infarction and a few cases were reported. We present the case of a 65-year-old Caucasian man with inferior and right ventricular myocardial infarction which was complicated by right ventricular rupture following successful percutaneous revascularization. The transthoracic echocardiography revealed right ventricular free wall rupture with pericardial effusion. The patient underwent a pericardial drainage by pericardiotomy without myocardial repair because of the self-limiting pattern of the right ventricular free wall rupture. The formation of a mural thrombus at the small rupture site limited the leakage and contributed to the outstanding favourable prognosis of the patient with early revascularization even without surgical repair.


Stimulus control of copulatory behavior in sexually naive male Japanese quail (Coturnix japonica): effects of test context and stimulus movement.
Sexually experienced male quail (Coturnix japonica) are more likely to engage in copulatory behavior than sexually naive ones. These experiments suggest that sexual experience in a particular place may facilitate later copulatory responding because of increased familiarity with the contextual cues of the environment. Male quail in Experiment 1 did not copulate reliably with taxidermic models of females in a novel context, even though some of the subjects were allowed to copulate with female quail in their home cages. In contrast, sexually naive males in Experiments 2 and 3 copulated vigorously with taxidermic models of females in a familiar context. In Experiment 4, sexually naive males tested in an unfamiliar context were more likely to copulate with a moving than with a static model. The stimulus control of copulatory behavior in sexually naive male quail was similar to that in sexually experienced ones but only in familiar contexts.


Severe asthma: follow-up after one year from the Italian Registry on Severe Asthma (IRSA)
Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.


The Development of TALE Nucleases for Biotechnology.
The development of a facile genome engineering technology based on transcription activator-like effector nucleases (TALENs) has led to significant advances in diverse areas of science and medicine. In this review, we provide a broad overview of the development of TALENs and the use of this technology in basic science, biotechnology, and biomedical applications. This includes the discovery of DNA recognition by TALEs, engineering new TALE proteins to diverse targets, general advances in nuclease-based editing strategies, and challenges that are specific to various applications of the TALEN technology. We review examples of applying TALENs for studying gene function and regulation, generating disease models, and developing gene therapies. The current status of genome editing and future directions for other uses of these technologies are also discussed.


Bipolar mood disorders: an affected sibling study. I. Genetic background and course of illness.
The study uses the 'affected (and hospitalized) siblings method' to investigate aspects of correlation in the psychopathology of bipolar mood disorders. In part one, age of onset, duration of phases, and course of illness are the points of interest. The sample includes 307 sibling groups (701 hospitalized individuals). The incidence of pure or schizoaffective type mania in at least 1 sibling has been the criterion for selection. The genetic background is also presented and the question is raised whether double tainting is the rule rather than the exception. The hypothesis that schizophrenic syndromes and mood disorders develop from separate genetic pools is supported. Strong evidence against the unipolar/bipolar dichotomy is presented. The investigation brings the breadth of the cyclothymic spectrum and inhomogeneity with respect to the course of bipolar disorders into perspective.


Calcific uremic arteriolopathy: overview for the nurse.
Calcific uremic arteriolopathy is a little understood diagnosis of increasing prevalence seen predominantly in patients with chronic kidney disease, particularly those who are approaching end-stage renal disease, who are undergoing renal dialysis, and who have secondary hyperparathyroidism. Calcific uremic arteriolopathy affects women more frequently than men, at a ratio of 3:1, and the median age at diagnosis is 48 years. A clear understanding of the pathogenesis and definitive plans of care are lacking. Nurses should be familiar with the clinical picture of calcific uremic arteriolopathy. Early recognition is important to develop optimal treatment plans and to limit progression of this rare but often fatal disease. Nurses have a pivotal role in maintaining the patient's comfort and dignity, while setting realistic goals of care. Calcific uremic arteriolopathy remains a rare and complex clinical condition that requires a multidisciplinary health care team approach to provide the optimal level of care. Nurses have an essential role in the care of patients with the diagnosis of calcific uremic arteriolopathy.


Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors.
Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics.


Lipid metabolism in the adipose tissues of a carnivore, the raccoon dog, during prolonged fasting.
Previous studies on laboratory rodents, rabbits, and humans have demonstrated that adipose tissue fatty acid (FA) mobilization is selective, and its efficiency is related to the molecular structure of FAs. This study was undertaken to find out whether such preferences of FA mobilization are a general feature of mammalian white adipose tissue (WAT) and are also manifested in carnivores. Fractional mobilization of a wide spectrum of FAs was studied by gas-liquid chromatography from six subcutaneous (scapular, rump, ventral) and intra-abdominal (omental, mesenteric, retroperitoneal) WAT depots of raccoon dogs (Nyctereutes procyonoides) fed or fasted for 2 months. Fasting stimulated the mobilization of shorter-chain saturated, mono-unsaturated (MUFAs), and polyunsaturated FAs (PUFAs). The effects of unsaturation and the position of the first double bond from the methyl end were more inconsistent. The effect of double-bond position may be due to chain shortening of longer-chain MUFAs and preferential utilization of n-3 PUFAs over n-6 PUFAs. Moreover, there were site-specific differences in fractional mobilization, the omental adipose tissue being the most divergent. The in vivo FA mobilization from the regional WAT depots of a carnivore was selective, and the molecular structure of the FA affected its efficiency.


Assessment of student's knowledge and awareness of autism spectrum disorder.
Developmental disorder as autism spectrum disorder (ASD) gives a specific image significantly deviating from the norm in the areas of social and communicative functioning of the child, including the ability to establish and maintain interpersonal relationships. It is difficult to determine the occurrence of autism in the world accurately. However, the WHO estimates one diagnosis in 160 children in the world. The aim of this study was to find how student's knowledge and awareness of autism spectrum disorder looks like. To assess awareness of autism was used the KCAHW questionnaire (Knowledge About Childhood Autism Among Health Workers). The research consisted of 446 people. Students in the second year of studies achieve lower results than those of the fourth and fifth year of studies. Students of medical faculties are characterised by lower awareness of disorder than students of pedagogical faculties. The social level of knowledge is low. Especially among healthcare providers that are directly related to ASD.


Superior mesenteric artery dissection: case report.
Spontaneous dissections of the superior mesenteric artery are exceptional events because only 26 reports have been published. We present a new case, revealed with an acute abdominal syndrome. Computed tomographic angiography and arteriography allowed a rapid diagnosis and urgent surgical intervention. Progress in imagery makes diagnosis and follow-up examination easier. Surgery is indicated for acute symptomatic forms with suspicion of mesenteric ischemia. In the other cases, a simple follow-up examination may be appropriate.


Primary ependymoma of a cranial nerve. Case report.
Ependymomas arising from peripheral or spinal nerves are extremely rare. Other ectopic ependymomas are found mostly in the sacrococcygeal region, possibly in association with developmental anomalies. The case of an ependymoma arising from a cranial nerve in a 40-year-old man is described.


Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP.
The Planar cell Polarity Effector (PPE) genes inturned, fuzzy, and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and dishevelled PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this. We previously found that mild overexpression of frtz rescued a weak in allele. To determine if this was due to extra Frtz stabilizing mutant In or due to Frtz being able to bypass the need for In we generate a precise deletion of the inturned gene (inPD ). We found that mild overexpression of Fritz partially rescued inPD , indicating that fritz has In independent activity in PCP. Previous studies of PPE proteins used fixed tissues, and did not provide any insights into the dynamic properties of PPE proteins. We used CRISPR/Cas9 genome editing technology to edit the fritz gene to add a green fluorescent protein tag. fritzmNeonGreen provides complete rescue activity and works well for in vivo imaging. Our data showed that Fritz is very dynamic in epidermal cells and preferentially distributed to discrete membrane subdomains ("puncta"). Surprisingly, we found it in stripes in developing bristles.


Ring Opening Metathesis Polymerisation (ROMP) as a tool for polyHIPes with extraordinary mechanical properties.
PolyHIPE materials have been prepared by Ring Opening Metathesis Polymerisation (ROMP) of dicyclopentadiene. Two characteristic features for successful stabilization of high internal phase emulsions (HIPEs) were tuned in order to achieve improvements regarding mechanical properties of polyHIPEs. Mechanical properties of the new materials were related to variations of the surfactant concentration and the volume ratio of the internal phase in HIPEs. Values for Young's moduli were about a hundred times higher than in standard polyHIPE materials with the same level of porosity, which represents a major improvement for highly porous cellular polymeric materials. Moreover, fully interconnected macroporous morphology was found for polyHIPEs, where respective HIPEs were stabilized with only 0.25 v% of surfactant.


Differences in the Early Development of Human and Mouse Embryonic Stem Cells.
We performed a systematic analysis of gene expression features in early (10-21 days) development of human vs mouse embryonic cells (hESCs vs mESCs). Many development features were found to be conserved, and a majority of differentially regulated genes have similar expression change in both organisms. The similarity is especially evident, when gene expression profiles are clustered together and properties of clustered groups of genes are compared. First 10 days of mESC development match the features of hESC development within 21 days, in accordance with the differences in population doubling time in human and mouse ESCs. At the same time, several important differences are seen. There is a clear difference in initial expression change of transcription factors and stimulus responsive genes, which may be caused by the difference in experimental procedures. However, we also found that some biological processes develop differently; this can clearly be shown, for example, for neuron and sensory organ development. Some groups of genes show peaks of the expression levels during the development and these peaks cannot be claimed to happen at the same time points in the two organisms, as well as for the same groups of (orthologous) genes. We also detected a larger number of upregulated genes during development of mESCs as compared to hESCs. The differences were quantified by comparing promoters of related genes. Most of gene groups behave similarly and have similar transcription factor (TF) binding sites on their promoters. A few groups of genes have similar promoters, but are expressed differently in two species. Interestingly, there are groups of genes expressed similarly, although they have different promoters, which can be shown by comparing their TF binding sites. Namely, a large group of similarly expressed cell cycle-related genes is found to have discrepant TF binding properties in mouse vs human.


Silver oxide nanowalls grown on Cu substrate as an enzymeless glucose sensor.
Ag(2)O nanowalls consisting of densely packed nanoplates based on a Cu substrate were synthesized through a facile one-pot hydrothermal method. A new enzymeless glucose sensor of Cu-Ag(2)O nanowalls was fabricated. The Cu-Ag(2)O nanowalls showed higher catalysis on glucose oxidation than traditional Ag(2)O nanoflowers and Cu-Ag(2)O nanospindles. At an applied potential of 0.4 V, the sensor produced an ultrahigh sensitivity to glucose (GO) of 298.2 microA mM(-1). Linear response was obtained over a concentration range from 0.2 mM to 3.2 mM with a detection limit of 0.01 mM (S/N = 3). Satisfyingly, the Cu-Ag(2)O nanowalls modified electrode was not only successfully employed to eliminate the interferences from uric acid (UA) acid ascorbic (AA) and also fructose (FO) during the catalytic oxidation of glucose. The Cu-Ag(2)O nanowalls modified electrode allows highly sensitive, excellently selective, stable, and fast amperometric sensing of glucose and thus is promising for the future development of nonenzymatic glucose sensors.


STAT1 gene expression is enhanced by nuclear EGFR and HER2 via cooperation with STAT3.
Both EGFR and HER2 are important mediators of tumorigenesis and tumor progression. Despite their best-characterized roles as plasma membrane-bound receptors, both receptors undergo nuclear translocation though the impact of this process remains unclear. In this study, we provide evidence showing that EGFR upregulates expression of signal transducer and activator of transcription 1 (STAT1), a transcription factor responding to inflammatory signals and regulating genes involved in inflammatory response. EGFR regulation of STAT1 expression is primarily attributed to the nuclear activity of EGFR. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression. Structural characterization of the human STAT1 gene promoter indicates the presence of four functional STAT3-binding sites in the promoter and their importance in STAT1 co-regulation by EGFR and STAT3. The constitutively activated EGFR variant, EGFRvIII, also cooperates with STAT3 to activate the STAT1 gene promoter through the identified STAT3-binding sites within the promoter. Using human breast cancer cell lines, we further found a positive association between levels of STAT1, EGFR, and p-STAT3. Furthermore, we found that STAT1 expression is transcriptionally upregulated by HER2 and heregulin stimulation in breast cancer cells, and the level is further augmented by activated STAT3. In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1.


[Surgical Safety of Elderly Hospitalized Patients Stratified by Age in General Surgery].
Objective To compare the surgical safety of elderly hospitalized patients in different age groups undergoing general surgery,and provide references for preoperative evaluation and treatment decision-making.Methods The inpatients ≥ 60 years old in the department of general surgery were selected from a national multi-center survey conducted from January to June in 2015 and from January to June in 2016.The patient characteristics and postoperative outcomes were described,and the risk factors for adverse postoperative outcomes of patients in different age groups were explored.Results The elderly patients (≥75 years old) accounted for 17.33%.The non-elderly patient (< 75 years old) group and the elderly patient (≥75 years old) group had significant differences in the proportions of patients with three or more chronical diseases (13.18% vs.5.36%,P<0.001),emergency surgery (16.64% vs.7.62%,P<0.001),American Society of Anesthesiologists score≥3 (48.68% vs.27.28%,P<0.001),and postoperative return to the intensive care unit(33.64% vs.12.00%,P<0.001).The occurrence of postoperative infectious complications showed no significant difference between the two age groups (7.29% vs.6.40%,P=0.410),while severe complications differed between the two groups (6.51% vs.2.60%,P<0.001).Besides,emergency surgery was a common independent risk factor for the two age groups.Conclusions Advanced age is not a contraindication to surgery of elderly patients.With consideration to patient's physical conditions and available surgical resources,elderly patients can still benefit from surgery.


A cloning strategy for the bacteriophage T4 vs gene.
The product of the bacteriophage T4 vs gene, the tau peptide, has been shown to thermally stabilize temperature-sensitive valyl-tRNA synthetase (EC 22.214.171.124). To clone the bacteriophage T4 vs gene, recombinant pBR322-T4 DNA molecules were used to transform Escherichia coli CP 790302 (valSts). Transformants that grew at 43.5 degrees C on selective medium exhibited some properties indicative of a phage-modified valyl-tRNA synthetase. The data are consistent with successful cloning of the vs gene and atypical modification of the valyl-tRNA synthetase in CP 790302.


Evaluation of an activity-centered health curriculum: assessment of cognitive knowledge.
This study was to determine how effective an activity-centered health curriculum was in providing health information to fourth, fifth and sixth-grade students in the Canton City school system. The assessment was facilitated by a posttest-only research design. Ten schools were randomly selected to receive a new health program, as compared to a control group of 10 schools which did not. Results indicated that the experimental students achieved significantly higher posttest cognitive knowledge mean scores than the control students. These findings were sustained for each grade level after adjusting for group differences in reading ability.


[Abscence of the tetrodotoxin effect on sodium permeability under conditions of prolonged depolarization].
Using frog muscle fibres, it is shown that 10(-6) tetrodotoxin does not practically affect the membrane permeability to lithium ions during a continious depolarization, with the membrane potential being near zero, but causes half a decreased lithium permeability under conditions of normal membrane potential. The absolute value of the lithium permeability for these two states are very close. A 10 mM tetraethylammonium chloride does not influence the lithium permeability of muscle membrane with the normal membrane potential and during a continious depolarization. It is proposed that intact and inactivated sodium channals may have almost equal ion passing capacities, but differ in their gate systems, especially as concerns its interaction with tetrodotoxin.


BRAF plus MEK-targeted drugs: a new standard of treatment for BRAF-mutant advanced melanoma.
BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients. Nevertheless, the development of mechanisms of resistance limits the duration of response to such treatment in the majority of cases, with only about 20% of patients treated with the combination being progression-free at 3 years. The aim of this review is to report the efficacy and safety outcomes of the combination of BRAF plus MEK inhibitors compared with BRAF inhibitor monotherapy and immunotherapy, as well as to discuss future perspectives to improve outcomes based on current clinical and translational research studies.


An attempt at predicting blood β-hydroxybutyrate from Fourier-transform mid-infrared spectra of milk using multivariate mixed models in Polish dairy cattle.
Fourier transform mid-infrared (FT-MIR) spectra of milk are commonly used for phenotyping of traits of interest through links developed between the traits and milk FT-MIR spectra. Predicted traits are then used in genetic analysis for ultimate phenotypic prediction using a single-trait mixed model that account for cows' circumstances at a given test day. Here, this approach is referred to as indirect prediction (IP). Alternatively, FT-MIR spectral variable can be kept multivariate in the form of factor scores in REML and BLUP analyses. These BLUP predictions, including phenotype (predicted factor scores), were converted to single-trait through calibration outputs; this method is referred to as direct prediction (DP). The main aim of this study was to verify whether mixed modeling of milk spectra in the form of factors scores (DP) gives better prediction of blood β-hydroxybutyrate (BHB) than the univariate approach (IP). Models to predict blood BHB from milk spectra were also developed. Two data sets that contained milk FT-MIR spectra and other information on Polish dairy cattle were used in this study. Data set 1 (n = 826) also contained BHB measured in blood samples, whereas data set 2 (n = 158,028) did not contain measured blood values. Part of data set 1 was used to calibrate a prediction model (n = 496) and the remaining part of data set 1 (n = 330) was used to validate the calibration models, as well as to evaluate the DP and IP approaches. Dimensions of FT-MIR spectra in data set 2 were reduced either into 5 or 10 factor scores (DP) or into a single trait (IP) with calibration outputs. The REML estimates for these factor scores were found using WOMBAT. The BLUP values and predicted BHB for observations in the validation set were computed using the REML estimates. Blood BHB predicted from milk FT-MIR spectra by both approaches were regressed on reference blood BHB that had not been used in the model development. Coefficients of determination in cross-validation for untransformed blood BHB were from 0.21 to 0.32, whereas that for the log-transformed BHB were from 0.31 to 0.38. The corresponding estimates in validation were from 0.29 to 0.37 and 0.21 to 0.43, respectively, for untransformed and logarithmic BHB. Contrary to expectation, slightly better predictions of BHB were found when univariate variance structure was used (IP) than when multivariate covariance structures were used (DP). Conclusive remarks on the importance of keeping spectral data in multivariate form for prediction of phenotypes may be found in data sets where the trait of interest has strong relationships with spectral variables.


The effects of serotonin on the differentiation of neurons producing vasoactive intestinal polypeptide in the suprachiasmatic nucleus of the rat.
The morphogenetic influences of serotonin on the differentiation of neurons synthesizing vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus were studied in rats. This was addressed by comparative morphofunctional analysis of VIP neurons in adult rats whose brains developed prenatally in conditions of normal and deficient serotonin metabolism. Serotonin deficiency was created in fetuses by treatment of their mothers with p-chlorophenylalanine (PCPA). Pregnant females in controls were treated with 0.9% NaCl. VIP neurons in experimental and control animals were found to show no differences in VIP mRNA concentrations and, probably, in the level of VIP synthesis. However, inhibition of serotonin synthesis led to an increase in the number of VIP-immunoreactive neurons and an increase in the VIP concentration within these cells. This was not associated with any change in neuron size, which was an indicator of the absence of functional hypertrophy accompanying activation of specific synthesis. Comparison of the data obtained here showed that during prenatal ontogenesis, serotonin has an imprinting influence on the differentiation of VIP neurons and is probably involved in the formation of the mechanism of VIP secretion.


Chemical synthesis of the 5'-terminal part bearing cap structure of messenger RNA of cytoplasmic polyhedrosis virus (CPV): m7G5'pppAmpG and m7G5'pppAmpGpU.
The 5'-terminal structures of mRNA bearing the so-called 'cap' from cytoplasmic polyhedrosis virus (CPV), m7G5' pppAmpG and m7G5' pppAmpGpU, were first chemically synthesized. S,S-Di(4-methoxyphenyl) N6-benzoyl-2'-O-methyladenosine 5'-phosphorodithioate ((ArS) 2pAbmz) was prepared by phosphorylation of the 5'-hydroxyl group of N6-benzoyl-2'-O-methyladenosine with S,S-di(4-methoxyphenyl) phosphorodithioate by TPS. By the triester approach using (ArS) 2pAbmz as starting material, the protected dinucleotide and trinucleotide bearing 5'-phosphate group were synthesized. The protective groups of the dinucleotide and trinucleotide were removed to obtain pAmpG and pAmpGpU, respectively. By the reaction of a capping agent ((PhS) ppm7G) with pAmpG and pAmpGpU in the presence of silver nitrate or iodine. The 5'-terminal structure of the messenger RNA strand of CPV which was labelled isotopically, was confirmed completely as m7G5' pppAmGpU by cochromatography with the materials chemically synthesized here.


Self-discontinuation of antiepileptic medication in pregnancy: detection by hair analysis.
Concerns over teratogenicity of antiepileptic drugs (AEDs) during pregnancy must be balanced against the risks of seizures to the mother and developing fetus. Pharmacokinetic changes and vomiting may alter drug levels, but more important may be the patient's decision to stop medication before or during pregnancy. Compliance assessment traditionally relies either on self-reporting or on AED plasma level monitoring; neither provides reliable information on drug-taking behaviour over an extended interval (e.g., before, during, and after pregnancy). We have used hair analysis to assess AED-taking behavior in pregnant women compared with nonpregnant female controls. Twenty-six pregnant women [mean age, 27.5 +/- 6.7 (SD) years] and 13 nonpregnant female epilepsy outpatients (mean age, 31.9 +/- 8.3 years) were studied. Carbamazepine (CBZ) or lamotrigine (LTG) concentrations were measured in 1-cm hair segments, and the within-subject variance in segmental hair concentrations of these drugs was calculated for each group. The variances of each group were then compared by using a variance ratio test. The variance of AED concentration in hair differed significantly between the pregnant and nonpregnant groups [variance ratio, 1.59 (p < 0.01)]. Four (15%) of the 26 pregnant patients had little or no AED in their proximal hair segments compared with more distal segments, apparently having discontinued their medication during pregnancy. Only one of these later disclosed having stopped her medication. One pregnant woman whose hair profile was similar to controls died suddenly at 30 weeks of gestation. This study confirms the perception that pregnant women with epilepsy frequently stop or greatly reduce their prescribed medication, usually without reference or acknowledgement to their clinician.


"Claw your way"--Machiavellianism among the medical community.
Machiavellianism is a personality trait characterized by emotional detachment and tendency to manipulate others to achieve one's own goal. It is presumed that people high in Machiavellianism would more likely choose business-related occupations, whereas low Machiavellians would prefer helping professions, therefore medical professionals are expected to be low-Machs. This is a questionnaire study on 509 respondents: medical school candidates (16.1%), medical students (65%), medical trainees (9.8%), residents (6.3%) and specialists (2.8%) aimed at assessing the level of Machiavellianism, as measured with Mach-IV score, a self-report questionnaire. The overall mean Mach-IV score was 59.24±6.07. The highest mean Mach-IV score, 61.80±6.94, was found in the group of medical school candidates. The lowest mean Mach-IV score, 57.61±7.88, was reported in the group of registered specialists. Male gender was found to be positively correlated with the mean Mach-IV score, which in women was 58.97±6.08 and in men it was 60.16±6.01. There was a negative correlation between the mean Mach-IV score and the age of post-graduate participants. When we divided all participants into subgroups of "low Machs" (<60 points) and " high Machs" (≥60 points), we found that both subgroups were similarly numerous--49.5% and 50.5%, accordingly. The highest representation of "high Machs" was found in the subgroup of medical studies candidates (65.85%), then in the students (47.73%) and in the group of post-graduates (45.16%). Gender differences remained statistically significant--47.33% of women and 60.18% of men were "high Machs". Machiavellianism level among medical candidates, students and doctors is relatively high, however is gradually decreasing with the progress of career.


[Soft tissue preservation and reconstruction in non-supporting foot parts].
The foot has two skin surfaces which differ on a morphological and functional basis. The plantar skin is a highly specialized organ which has a dash-pot-like effect in weight bearing. The skin which does not participate in weight bearing covers tendons and a very rich syndesmotic complex. The internal soft tissue is segmented in tiny compartments and therefore ist not extensible. The skin and the rather thin subcutaneous layer are not extensible either because of the proximity and the rigidity of the underlying structures. In consequence, trauma to the soft tissue of the foot may cause compartment syndromes and skin defects, or secondary unstable scars which impede function. Compartment syndromes must be recognized early and treated by immediate release. Fresh skin defects need early coverage when tendons and joints are exposed. There is a variety of local flaps which are evenly good for replacement of retracting scars.


The vibronic level structure of the cyclopentadienyl radical.
The 351.1 nm photoelectron spectrum of the cyclopentadienide ion has been measured, which reveals the vibronic structure of the X (2)E(1) (") state of the cyclopentadienyl radical. Equation-of-motion ionization potential coupled-cluster (EOMIP-CCSD) calculations have been performed to construct a diabatic model potential of the X (2)E(1) (") state, which takes into account linear Jahn-Teller effects along the e(2) (') normal coordinates as well as bilinear Jahn-Teller effects along the e(2) (') and ring-breathing a(1) (') coordinates. A simulation based on this ab initio model potential reproduces the spectrum very well, identifying the vibronic levels with linear Jahn-Teller angular momentum quantum numbers of +/-1/2. The angular distributions of the photoelectrons for these vibronic levels are highly anisotropic with the photon energies used in the measurements. A few additional weak photoelectron peaks are observed when photoelectrons ejected parallel to the laser polarization are examined. These peaks correspond to the vibronic levels for out-of-plane modes in the ground X (2)E(1) (") state, which arise due to several pseudo-Jahn-Teller interactions with excited states of the radical and quadratic Jahn-Teller interaction in the X (2)E(1) (") state. A variant of the first derivative of the energy for the EOMIP-CCSD method has been utilized to evaluate the strength of these nonadiabatic couplings, which have subsequently been employed to construct the model potential of the X (2)E(1) (") state with respect to the out-of-plane normal coordinates. Simulations based on the model potential successfully reproduce the weak features that become conspicuous in the 0 degrees spectrum. The present study of the photoelectron spectrum complements a previous dispersed fluorescence spectroscopic study by Miller and co-workers [J. Chem. Phys. 114, 4855 (2001); 114, 4869 (2001)] to provide a detailed account of the vibronic structure of X (2)E(1) (") cyclopentadienyl. The electron affinity of the cyclopentadienyl radical is determined to be 1.808+/-0.006 eV. This electron affinity and the gas-phase acidity of cyclopentadiene have been combined in a negative ion thermochemical cycle to determine the C-H bond dissociation energy of cyclopentadiene; D(0)(C(5)H(6),C-H)=81.5+/-1.3 kcal mol(-1). The standard enthalpy of formation of the cyclopentadienyl radical has been determined to be Delta(f)H(298)(C(5)H(5))=63.2+/-1.4 kcal mol(-1).