Oral prostaglandin E2 for labor induction in high-risk pregnancy.
Oral prostaglandin E2 (PGE2) was used alone or synergistically with intravenous oxytocin to induce labor in 84 women whose pregnancies were at high risk. A control group of 84 similar high-risk pregnancies where labor was induced with intravenous oxytocin alone was studied to compare the safety and efficacy of the two regimens. Oral PGE2 administration, combined with the synergistic effect of intravenous oxytocin, is safe for induction of labor in gravid women whose fetuses are at risk. Uterine polysystole, which is potentially dangerous, especially to the high-risk fetus, was not commonly encountered and only once was associated with transient fetal bradycardia. Uterine hypertonus was not encountered with PGE2; however, it did occur with oxytocin stimulation. Nausea and vomiting occurred in one third of the women treated with PGE2 but were well tolerated and required discontinuation of the drug in only one instance. There was no apparent advantage of using the combination PGE2 regimen in patients whose cervices were more favorable for induction of labor (Bishop score, 5 to 9). However, oral PGE2, used either alone or synergistically with oxytocin, appears twice as effective in inducing labor than was oxytocin alone in women in whom labor was considered to be "difficult to induce" (Bishop score, 0 to 4).


Particle-attached and free-living bacterial communities in a contrasting marine environment: Victoria Harbor, Hong Kong.
Diversity of particle-attached and free-living marine bacteria in Victoria Harbor, Hong Kong, and its adjacent coastal and estuarial environments was investigated using DNA fingerprinting and clone library analysis. Denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA genes showed that bacterial communities in three stations of Victoria Harbor were similar, but differed from those in adjacent coastal and estuarine stations. Particle-attached and free-living bacterial community composition differed in the Victoria Harbor area. DNA sequencing of 28 bands from DGGE gel showed Alphaproteobacteria was the most abundant group, followed by the Bacteroidetes, and other Proteobacteria. Bacterial species richness (number of DGGE bands) differed among stations and populations (particle-attached and free-living; bottom and surface). BIOENV analysis indicated that the concentrations of suspended solids were the major contributing parameter for the spatial variation of total bacterial community structure. Samples from representative stations were selected for clone library (548 clones) construction and their phylogenetic distributions were similar to those of sequences from DGGE. Approximately 80% of clones were affiliated to Proteobacteria, Bacteroidetes and Cyanobacteria. The possible influences of dynamic pollution and hydrological conditions in the Victoria Harbor area on the particle-attached and free-living bacterial community structures were discussed.


Two functionally distinct networks of gap junction-coupled inhibitory neurons in the thalamic reticular nucleus.
Gap junctions (GJs) electrically couple GABAergic neurons of the forebrain. The spatial organization of neuron clusters coupled by GJs is an important determinant of network function, yet it is poorly described for nearly all mammalian brain regions. Here we used a novel dye-coupling technique to show that GABAergic neurons in the thalamic reticular nucleus (TRN) of mice and rats form two types of GJ-coupled clusters with distinctive patterns and axonal projections. Most clusters are elongated narrowly along functional modules within the plane of the TRN, with axons that selectively inhibit local groups of relay neurons. However, some coupled clusters have neurons arrayed across the thickness of the TRN and target their axons to both first- and higher-order relay nuclei. Dye coupling was reduced, but not abolished, among cells of connexin36 knock-out mice. Our results suggest that GJs form two distinct types of inhibitory networks that correlate activity either within or across functional modules of the thalamus.


Incidence of headache after COVID-19 vaccination in patients with history of headache: A cross-sectional study.
Headache is an adverse event of coronavirus 2019 (COVID-19) vaccination. Whether patients with history of headache suffer more from vaccination-induced headaches is unknown. We aimed to uncover if headache patients develop more headaches after COVID-19 mRNA vaccination than healthy controls. We performed a questionnaire survey for nursing staff in our hospital from April to May 2021. Based on baseline characteristics, we divided the participants into migraine, non-migrainous headache, and healthy control, and examined the occurrence and features of headache after COVID-19 vaccinations. We included 171 participants (15.2% migraine and 24.6% non-migrainous headache). Headache incidence after vaccinations was significantly higher in the migraine (69.2%) and non-migrainous headache (71.4%) groups than in the healthy control (37.9%) group. The incidence of headaches was significantly higher after the second dose compared to the first (45.6% vs. 20.5%). Migraineurs and non-migrainous headache participants developed more headaches compared to the healthy controls after COVID-19 vaccination.


Outcomes of colorectal cancer arising in solid organ transplant recipients.
The incidence of colorectal cancer posttransplantation is unclear. Limited reports exist and have conflicting conclusions. We aimed to review the clinical features and oncologic outcomes of colorectal cancer in transplant recipients at our institution. A retrospective review of all patients diagnosed with colorectal cancer after solid organ transplantation between 2000 and 2011 was conducted. Clinical features and outcomes were reviewed. Twenty of 3,946 patients were identified. The most common single organ transplanted was the kidney (n = 8). Six patients had multiorgan transplantation. Median age of diagnosis of cancer was 64.3 years, and median time from transplant to diagnosis of cancer was 8.7 years. Ten patients were symptomatic at presentation. Cancer was identified on routine colonoscopy in seven patients. Tumors were most commonly found in the right colon (n = 14, 70%). Six patients had stage IV disease at presentation. Short-term morbidity was identified in 11 patients. Postoperative mortality occurred in one patient. Median follow-up was 2.47 years. Overall survival at 5 years was 69%, and disease-free survival was 68 %. Distant recurrence was seen in 3 (15%) patients. Colorectal cancer in these patients is rare, and surgery can be done safely. Vigilant screening must be maintained in this patient population.


Antiphospholipid syndrome.
The antiphospholipid syndrome (APS) is defined by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPLs). Catastrophic APS is the most severe form of APS, which is associated with rapid development of microvascular thrombosis resulting in multiorgan failure in patients with aPLs. Patients with APS and catastrophic APS are recognized to have a high risk of recurrent thrombosis that can occur despite anticoagulant therapy. Although antithrombotic therapy remains the mainstay of treatment, bleeding manifestations can complicate management and contribute to increased morbidity. Patients with persistently elevated aPL levels, particularly those who exhibit positive testing for lupus anticoagulant, anticardiolipin antibodies, and anti-β2GPI antibodies (triple positivity), appear to be at increased risk for thrombosis and pregnancy complications, whereas isolated positivity for aPLs appears to be associated with low risk. Recognizing that patients with APS have different thrombotic risk profiles may assist clinicians in assessing the risks and benefits of anticoagulation. The optimal type, intensity, and duration of anticoagulation in the treatment of APS remain controversial, particularly for arterial thrombosis and recurrent thrombosis. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.


On the processive mechanism of Escherichia coli DNA polymerase I. Delayed initiation of polymerization.
Escherichia coli DNA polymerase I shows a delay in the initiation of polymerization after binding to the cohesive ends of lambda DNA. This delay is significantly longer than the time required for the synthesis of an octanucleotide sequence on the right-hand cohesive end of the lambda DNA. When the extent of polymerization is limited by omission of one or more of the deoxynucleoside triphosphates, and polymerization started again by their addition, the delay still occurs. A plausible explanation for this phenomenon is that two forms of the enzyme or enzyme - DNA complex exist, only one of which is active. The delay, therefore, represents the time necessary to convert the inactive to the active form of the enzyme or enzyme complex. One consequence of the defect in DNA polymerase I, due to the polA12 mutation, is apparently to alter the equilibrium between the two forms. However, the rate of polymerization and the rate of conversion of inactive to active enzyme or enzyme complex are not changed significantly.


Economic and Clinical Burden of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes in the U.S.
Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NASH have increased risk for adverse clinical outcomes, leading to higher risk for mortality and morbidity. We built a Markov model with 1-year cycles and 20-year horizon to estimate the economic burden of NASH with T2DM in the U.S. Cohort size was determined by population size, prevalence of T2DM, and prevalence and incidence of NASH in 2017. The model includes 10 health states-NAFL, NASH fibrosis stages F0 through F3, compensated and decompensated cirrhosis, hepatocellular carcinoma, 1 year post-liver transplant, and post-liver transplant-as well as liver-related, cardiovascular, and background mortality. Transition probabilities were calculated from meta-analyses and literature. Annual costs for NASH and T2DM were taken from literature and billing codes. We estimated that there were 18.2 million people in the U.S. living with T2DM and NAFLD, of which 6.4 million had NASH. Twenty-year costs for NAFLD in these patients were $55.8 billion. Over the next 20 years, NASH with T2DM will account for 65,000 transplants, 1.37 million cardiovascular-related deaths, and 812,000 liver-related deaths. This model predicts significant clinical and economic burden due to NASH with T2DM over the next 20 years. In fact, this burden may be greater since we assumed conservative inputs for our model and did not increase costs or the incidence of T2DM over time. It is highly likely that interventions reducing morbidity and mortality in NASH patients with T2DM could potentially reduce this projected clinical and economic burden.


Angiotensin type-1 receptor blockers in heart failure.
Chronic heart failure is a common condition with a poor prognosis, usually associated with poor exercise tolerance and debilitating symptoms despite optimal modern therapy. Standard therapy includes diuretics, digoxin, angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers. Despite this, many patients remain symptomatic, and interest is high as to whether the angiotensin receptor blockers (ARBs) would offer further advantage to a patient already receiving quadruple therapy. In addition, some patients are intolerant of ACEIs, and for this group the ARBs seem a logical choice. This article reviews the evidence for the use of ARBs as a class in heart failure concentrating on clinical recommendations and clinical needs and evidence rather than purely on statistical issues of significance in trials. The trials to date have demonstrated clearly similar hemodynamic effects to those seen with ACEIs and variety of ancillary benefits such as improvements in endothelial function, anti-thrombotic effects, and effects on neurohormonal inhibition. There is consistent evidence of a preservation of exercise tolerance when patients with heart failure are crossed over from stable ACEI therapy, and when added to ACEIs exercise tolerance appears to increase with ARBs. In terms of major outcomes, the two largest trials, Elite-II and Val-Heft, demonstrate that angiotensin receptor blockers probably have a clinical role in improving mortality and morbidity as an alternative to ACEIs in those patients unable to tolerate these agents, which remain, however, the first choice in unselected patients with heart failure. There is a worrying suggestion of a negative interaction when ARBs are added to beta-blockers, which is a reason for caution in using the ARBs, not a reason not to use beta-blockers.


Ensuring electronic medical record simulation through better training, modeling, and evaluation.
Electronic medical records (EMRs) can support medical research and discovery, but privacy risks limit the sharing of such data on a wide scale. Various approaches have been developed to mitigate risk, including record simulation via generative adversarial networks (GANs). While showing promise in certain application domains, GANs lack a principled approach for EMR data that induces subpar simulation. In this article, we improve EMR simulation through a novel pipeline that (1) enhances the learning model, (2) incorporates evaluation criteria for data utility that informs learning, and (3) refines the training process. We propose a new electronic health record generator using a GAN with a Wasserstein divergence and layer normalization techniques. We designed 2 utility measures to characterize similarity in the structural properties of real and simulated EMRs in the original and latent space, respectively. We applied a filtering strategy to enhance GAN training for low-prevalence clinical concepts. We evaluated the new and existing GANs with utility and privacy measures (membership and disclosure attacks) using billing codes from over 1 million EMRs at Vanderbilt University Medical Center. The proposed model outperformed the state-of-the-art approaches with significant improvement in retaining the nature of real records, including prediction performance and structural properties, without sacrificing privacy. Additionally, the filtering strategy achieved higher utility when the EMR training dataset was small. These findings illustrate that EMR simulation through GANs can be substantially improved through more appropriate training, modeling, and evaluation criteria.


Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity.
Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers. We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001-2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls. Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in "in vitro" assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients. Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.


Role of Physicochemical Properties of Protein in Modulating the Nanoparticle-Bio Interface.
Nanoparticles, on exposure to the biological milieu, tend to interact with macromolecules to form a biomolecular corona. The biomolecular corona confers a unique biological identity to nanoparticles, and its protein composition plays a deterministic role in the biological fate of nanoparticles. The physiological behavior of proteins stems from their physicochemical properties, including surface charge, hydrophobicity, and structural stability. However, there is insufficient understanding about the role of physicochemical properties of proteins in biomolecular corona formation. We hypothesized that the physicochemical properties of proteins would influence their interaction with nanoparticles and have a deterministic effect on nanoparticle-cell interactions. To test our hypothesis, we used model proteins from different structural classes to understand the effect of secondary structure elements of proteins on the nanoparticle-protein interface. Further, we modified the surface of proteins to study the role of protein surface characteristics in governing the nanoparticle-protein interface. For this study, we used mesoporous silica nanoparticles as a model nanoparticle system. We observed that the surface charge of proteins governs the nature of the primary interaction and the extent of subsequent secondary interactions causing structural rearrangements of the protein. We also observed that the secondary structural contents of proteins significantly affected both the extent of secondary interactions at the nanoparticle-protein interface and the dispersion state of the nanoparticle-protein complex. Further, we studied the interactions of different protein-coated nanoparticles with different cells (fibroblast, carcinoma, and macrophage). We observed that different cells internalized the nanoparticle-protein complex as a function of secondary structural components of the protein. The type of model protein had a significant effect on their internalization by macrophages. Overall, we observed that the physicochemical characteristics of proteins had a significant role in modulating the nanoparticle-bio-interface at the level of both biomolecular corona formation and nanoparticle internalization by cells.


Vascularized and Innervated Skeletal Muscle Tissue Engineering.
Volumetric muscle loss (VML) is a devastating loss of muscle tissue that overwhelms the native regenerative properties of skeletal muscle and results in lifelong functional deficits. There are currently no treatments for VML that fully recover the lost muscle tissue and function. Tissue engineering presents a promising solution for VML treatment and significant research has been performed using tissue engineered muscle constructs in preclinical models of VML with a broad range of defect locations and sizes, tissue engineered construct characteristics, and outcome measures. Due to the complex vascular and neural anatomy within skeletal muscle, regeneration of functional vasculature and nerves is vital for muscle recovery following VML injuries. This review aims to summarize the current state of the field of skeletal muscle tissue engineering using 3D constructs for VML treatment with a focus on studies that have promoted vascular and neural regeneration within the muscle tissue post-VML.


Bioaccumulation, distribution and elimination of chlordecone in the giant freshwater prawn Macrobrachium rosenbergii: Field and laboratory studies.
Chlordecone is a persistent organochlorine pesticide that has been widely used in Guadeloupe (French West Indies) to control the banana weevil Cosmopolites sordidus from 1972 to 1993. A few years after its introduction, widespread contamination of soils, rivers, wild animals and aquatic organisms was reported. Although high chlordecone concentrations have been reported in several crustacean species, its uptake, internal distribution, and elimination in aquatic species have never been described. This study aimed at investigating the accumulation and tissue distribution of chlordecone in the giant freshwater prawn Macrobrachium rosenbergii, using both laboratory (30 days exposure) and field (8 months exposure) approaches. In addition, depuration in chlordecone-free water was studied. Results showed that chlordecone bioconcentration in prawns was dose-dependent and time-dependent. Moreover, females appeared to be less contaminated than males after 5 and 7 months of exposure, probably due to successive spawning leading in the elimination of chlordecone through the eggs. Chlordecone distribution in tissues of exposed prawns showed that cephalothorax organs, mainly represented by the hepatopancreas, was the most contaminated. Results also showed that chlordecone was accumulated in cuticle, up to levels of 40% of the chlordecone body burden, which could be considered as a depuration mechanism since chlordecone is eliminated with the exuviae during successive moults. Finally, this study underlined the similarity of results obtained in laboratory and field approaches, which highlights their complementarities in the chlordecone behaviour understanding in M. rosenbergii.


Initial Experience Using Disposable Negative Pressure Wound Therapy for Closed Incisions Following Outpatient Wound Reconstruction.
Wound reconstruction surgeries are at high risk for failure. Outpatient wound reconstruction (OWR) describes these procedures performed in the outpatient setting under local anesthesia. The use of closed incision negative pressure therapy (ciNPT) has been shown to protect the incision and help minimize the risk of postoperative complications. To date, this has not been readily adopted in the outpatient setting. The authors report their initial experience with 3 cases of OWR with ciNPT used by the application of disposable negative pressure wound therapy (dNPWT) to the closed, postsurgical incision. The results of these 3 cases were favorable. While more data are needed, the authors believe the use of dNPWT with OWR will help optimize surgical outcomes and serve as an alternative to surgery with acute hospitalization.


The prognostic influence of neuroendocrine differentiation in breast cancer: results of a long-term follow-up study.
Reports about neuroendocrine (NE) differentiation in breast carcinomas and its possible relation with prognosis are scarce. Furthermore the results of some studies have not been subjected to multivariate survival analysis and the follow-up periods were relatively short. Therefore, in the present long-term follow-up study, the prognostic influence of immunohistochemically defined NE cells, present in the tumours of 40 out of 317 (12.6%) curatively operated breast cancer patients, was studied. The mean follow-up period was 104 months. NE differentiation (NED) was determined by the immunohistochemical detection of chromogranin A and/or synaptophysin. This is concordant with other studies focussing on NED in breast cancer. In contrast to the literature in our series only in 9 out of 40 cases (23%) we were able to detect coexpression of chromogranin A and synaptophysin. This might be due to the characteristics of the antibodies we used. Although most tumours in our series were of the usual type, some tumours with NED were of a special type. Neither univariately, nor taking account of various known prognostic factors, does focal NED appear to carry a special prognostic significance. This finding is in line with results of previous studies.


2-Methoxyestradiol inhibits high fat diet-induced obesity in rats through modulation of adipose tissue macrophage infiltration and immunophenotype.
Recently, experimental studies demonstrated that 2-methoxyestradiol (2ME2) ameliorates high fat diet (HFD)-induced obesity and restores insulin sensitivity. However, the mechanisms underlying these effects are unveiled yet. The current study was undertaken to test the hypothesis that 2ME2 exerts its effects by modulating adipose tissue macrophages (ATMs) accumulation, polarization and immunophenotypes. The experiment was carried out in males Wistar rats (n = 28) for 13 consecutive weeks. In HFD-fed group; body weight, glucose intolerance, serum insulin, HOMA-IR, lipid profile and adipose tissue (AT) weight were significantly higher compared to normal standard diet (NSD)- fed rats. However, treatment of HFD-fed rats with 2ME2 (200 μg/kg/day; i.p. from the beginning of the 9th week) resulted in significant enhancements in all these parameters as compared to HFD-fed rats. Treatment with 2ME2 was associated with a significant reduction in macrophage infiltration in the AT, shifting macrophage polarization towards M2 phenotype as indicated by significant decrease in the expression of pro-inflammatory M1 macrophages markers (IL-6, IL-1β, CD11c and iNOS) and concurrent significant increase in the M2 anti-inflammatory macrophage markers (Arginase 1 and IL-10). 2ME2 ameliorates HFD-induced obesity and glucose intolerance through inhibition of ATM infiltration in AT and shifting macrophage polarization from pro-inflammatory M1 to M2 anti-inflammatory phenotypes.


What social workers can do about violence: learnings from the lives of 37 men.
Descriptive results of a study of the lives of 37 men who were executed for capital murder reveal the complex and multi-varied problem of violence at individual, institutional, and societal levels. The role of social workers is discussed in relation to prevention of violent crime rather than focusing on punishment. The study provides support for an anti-death penalty policy stance by the social work profession.


#MedToo: A Large-Scale Examination of the Incidence and Impact of Sexual Harassment of Physicians and Other Faculty at an Academic Medical Center.
Background: A landmark National Academies report highlighted the need for rigorous evaluation of sexual harassment in medicine. We examined the prevalence and impact of sexual harassment using the Sexual Experiences Questionnaire, the standard for measurement of sexual harassment, but which has not been previously applied within academic medicine. Materials and Methods: A 20-minute online survey was administered to all faculty who had been working at University of Michigan Medical School for at least 1 year (n = 2723). We assessed sexual harassment within the past year from insiders (i.e., from staff, students, and faculty) and from patients and patients' families. We also evaluated mental health, job satisfaction, sense of safety at work, and turnover intentions. Results: In the final sample (n = 705; which included 25.9% of the originally targeted population), most respondents, 82.5% of women and 65.1% of men, reported at least one incident of sexual harassment from insiders in the past year; 64.4% of women and 44.1% of men reported harassment from patients and patients' families. The most frequently experienced dimension of sexual harassment for women and men was sexist gender harassment. Increased experiences of harassment were independently associated with lower mental health, job satisfaction, and sense of safety at work, as well as increased turnover intentions, with no significant interactions by gender. Conclusions: Sexual harassment against medical faculty is alarmingly common at an institution that is not expected to be atypical. Interventions must address sexual harassment, which affects mental health and career outcomes of male and female physicians.


The Validity of Scores From the New MCAT Exam in Predicting Student Performance: Results From a Multisite Study.
The new Medical College Admission Test (MCAT) was introduced in April 2015. This report presents findings from the first study of the validity of scores from the new MCAT exam in predicting student performance in the first year of medical school (M1). The authors analyzed data from the national population of 2016 matriculants with scores from the new MCAT exam (N = 7,970) and the sample of 2016 matriculants (N = 955) from 16 medical schools who volunteered to participate in the validity research. They examined correlations of students' MCAT total scores and total undergraduate grade point averages (UGPAs), alone and together, with their summative performance in M1, and the success rate of students with different MCAT scores in their on-time progression to the second year of medical school (M2). They assessed whether MCAT scores provided comparable prediction of performance in M1 by students' race/ethnicity, socioeconomic background, and gender. Correlations of MCAT scores with summative performance in M1 ranged from medium to large. Although MCAT scores and UGPAs provided similar prediction of performance in M1, using both metrics provided better prediction than either alone. Additionally, students with a wide range of MCAT scores progressed to M2 on time. Finally, MCAT scores provided comparable prediction of performance in M1 for students from different sociodemographic backgrounds. This study provides early evidence that scores from the new MCAT exam predict student performance in M1. Future research will examine the validity of MCAT scores in predicting performance in later years.


What Does Stock Ownership Breadth Measure?
Using holdings data on a representative sample of all Shanghai Stock Exchange investors, we show that increases in ownership breadth (the fraction of market participants who own a stock) predict low returns: highest change quintile stocks underperform lowest quintile stocks by 23% per year. Small retail investors drive this result. Retail ownership breadth increases appear to be correlated with overpricing. Among institutional investors, however, the opposite holds: Stocks in the top decile of wealth-weighted institutional breadth change outperform the bottom decile by 8% per year, consistent with prior work that interprets breadth as a measure of short-sales constraints.


Borderline ovarian tumor - a case report with genetic testing.
Despite an accurate classification, the borderline category of ovarian tumors is one of the most controversial topics in gynecologic oncology and is confusing to both clinicians and patients. The treatment is often confronted with the necessity of a fertility-sparing approach, although under-treatment increases the risk of disease recurrence. The clear definition of a group of patients with low or high risk of relapse requiring more or less extensive treatment is lacking. Currently, the main criteria affecting the treatment extent include histopathological features, particularly the presence of microinvasion, and invasive implants. Expansion of knowledge about genetic nature of the tumor characteristics may more closely specify the scope of therapeutic approach for individual patients. The authors report a case report of serous borderline ovarian tumor patient with tumor cell dispersion into the gastrointestinal tract. The genes of tumor vascular markers GPM6B and DR6 were also studied and compared to a group of healthy patients.


Maternal antibiotic prophylaxis affects Bifidobacterium spp. counts in the human milk, during the first week after delivery.
Human milk is an important source of microorganisms for infant gut colonisation. Although the maternal antibiotic prophylaxis is an important strategy to prevent maternal/neonatal sepsis, it has to be investigated how it may affect the human milk microbiota, especially the genus Bifidobacterium, which has been associated to health benefits. Here, we investigated the impact of the maternal antibiotic prophylaxis on the human milk Bifidobacterium spp. and total bacteria counts, in the first week (short-term) and first month (medium-term) after delivery. Human milk samples were collected from 55 healthy lactating women recruited from the University Hospital of the University of São Paulo at days 7±3 and 30±4 after vaginal delivery. Twenty one volunteers had received maternal antibiotic prophylaxis (MAP group) and 34 had not received MAP (no-MAP group) during or after labour. Total DNA was isolated from milk samples, and the bacterial counts were estimated by quantitative PCR (qPCR). We found lower levels of Bifidobacterium in the MAP group in the first week after delivery (median = 2.1 vs 2.4 log of equivalent cells/ml of human milk, for MAP and no-MAP groups, respectively; P=0.01), although there were no statistical differences in total bacteria count. However, no differences were found in Bifidobacterium counts between the groups at day 30±4 (median = 2.5 vs 2.2 log of equivalent cells/ml of human milk, for MAP and no-MAP groups, respectively; P=0.50). Our results suggest that MAP has a significant impact on Bifidobacterium counts in human milk, reducing this population in the first week after delivery. However, throughout the first month after delivery, the Bifidobacterium counts tend to recover, reaching similar counts to those found in no-MAP group at day 30±4 after delivery.


Evaluation of grain boundaries as percolation pathways in quartz-rich continental crust using Atomic Force Microscopy.
Hydrous fluids play a vital role in the chemical and rheological evolution of ductile, quartz-bearing continental crust, where fluid percolation pathways are controlled by grain boundary domains. In this study, widths of grain boundary domains in seven quartzite samples metamorphosed under varying crustal conditions were investigated using Atomic Force Microscopy (AFM) which allows comparatively easy, high magnification imaging and precise width measurements. It is observed that dynamic recrystallization at higher metamorphic grades is much more efficient at reducing grain boundary widths than at lower temperature conditions. The concept of force-distance spectroscopy, applied to geological samples for the first time, allows qualitative estimation of variations in the strength of grain boundary domains. The strength of grain boundary domains is inferred to be higher in the high grade quartzites, which is supported by Kernel Average Misorientation (KAM) studies using Electron Backscatter Diffraction (EBSD). The results of the study show that quartzites deformed and metamorphosed at higher grades have narrower channels without pores and an abundance of periodically arranged bridges oriented at right angles to the length of the boundary. We conclude that grain boundary domains in quartz-rich rocks are more resistant to fluid percolation in the granulite rather than the greenschist facies.


Distinct molecular etiologies of male and female hepatocellular carcinoma.
Sex-differences in cancer occurrence and mortality are evident across tumor types; men exhibit higher rates of incidence and often poorer responses to treatment. Targeted approaches to the treatment of tumors that account for these sex-differences require the characterization and understanding of the fundamental biological mechanisms that differentiate them. Hepatocellular Carcinoma (HCC) is the second leading cause of cancer death worldwide, with the incidence rapidly rising. HCC exhibits a male-bias in occurrence and mortality, but previous studies have failed to explore the sex-specific dysregulation of gene expression in HCC. Here, we characterize the sex-shared and sex-specific regulatory changes in HCC tumors in the TCGA LIHC cohort using combined and sex-stratified differential expression and eQTL analyses. By using a sex-specific differential expression analysis of tumor and tumor-adjacent samples, we uncovered etiologically relevant genes and pathways differentiating male and female HCC. While both sexes exhibited activation of pathways related to apoptosis and cell cycle, males and females differed in the activation of several signaling pathways, with females showing PPAR pathway enrichment while males showed PI3K, PI3K/AKT, FGFR, EGFR, NGF, GF1R, Rap1, DAP12, and IL-2 signaling pathway enrichment. Using eQTL analyses, we discovered germline variants with differential effects on tumor gene expression between the sexes. 24.3% of the discovered eQTLs exhibit differential effects between the sexes, illustrating the substantial role of sex in modifying the effects of eQTLs in HCC. The genes that showed sex-specific dysregulation in tumors and those that harbored a sex-specific eQTL converge in clinically relevant pathways, suggesting that the molecular etiologies of male and female HCC are partially driven by differential genetic effects on gene expression. Sex-stratified analyses detect sex-specific molecular etiologies of HCC. Overall, our results provide new insight into the role of inherited genetic regulation of transcription in modulating sex-differences in HCC etiology and provide a framework for future studies on sex-biased cancers.


Pressure support versus T-tube for weaning from mechanical ventilation in adults.
Mechanical ventilation is important in caring for patients with critical illness. Clinical complications, increased mortality, and high costs of health care are associated with prolonged ventilatory support or premature discontinuation of mechanical ventilation. Weaning refers to the process of gradually or abruptly withdrawing mechanical ventilation. The weaning process begins after partial or complete resolution of the underlying pathophysiology precipitating respiratory failure and ends with weaning success (successful extubation in intubated patients or permanent withdrawal of ventilatory support in tracheostomized patients). To evaluate the effectiveness and safety of two strategies, a T-tube and pressure support ventilation, for weaning adult patients with respiratory failure that required invasive mechanical ventilation for at least 24 hours, measuring weaning success and other clinically important outcomes. We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6); MEDLINE (via PubMed) (1966 to June 2012); EMBASE (January 1980 to June 2012); LILACS (1986 to June 2012); CINAHL (1982 to June 2012); SciELO (from 1997 to August 2012); thesis repository of CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) (http://capesdw.capes.gov.br/capesdw/) (August 2012); and Current Controlled Trials (August 2012).We reran the search in December 2013. We will deal with any studies of interest when we update the review. We included randomized controlled trials (RCTs) that compared a T-tube with pressure support (PS) for the conduct of spontaneous breathing trials and as methods of gradual weaning of adult patients with respiratory failure of various aetiologies who received invasive mechanical ventilation for at least 24 hours. Two authors extracted data and assessed the methodological quality of the included studies. Meta-analyses using the random-effects model were conducted for nine outcomes. Relative risk (RR) and mean difference (MD) or standardized mean difference (SMD) were used to estimate the treatment effect, with 95% confidence intervals (CI). We included nine RCTs with 1208 patients; 622 patients were randomized to a PS spontaneous breathing trial (SBT) and 586 to a T-tube SBT. The studies were classified into three categories of weaning: simple, difficult, and prolonged. Four studies placed patients in two categories of weaning. Pressure support ventilation (PSV) and a T-tube were used directly as SBTs in four studies (844 patients, 69.9% of the sample). In 186 patients (15.4%) both interventions were used along with gradual weaning from mechanical ventilation; the PS was gradually decreased, twice a day, until it was minimal and periods with a T-tube were gradually increased to two and eight hours for patients with difficult and prolonged weaning. In two studies (14.7% of patients) the PS was lowered to 2 to 4 cm H2O and 3 to 5 cm H2O based on ventilatory parameters until the minimal PS levels were reached. PS was then compared to the trial with the T-tube (TT).We identified 33 different reported outcomes in the included studies; we took 14 of them into consideration and performed meta-analyses on nine. With regard to the sequence of allocation generation, allocation concealment, selective reporting and attrition bias, no study presented a high risk of bias. We found no clear evidence of a difference between PS and TT for weaning success (RR 1.07, 95% CI 0.97 to 1.17, 9 studies, low quality of evidence), intensive care unit (ICU) mortality (RR 0.81, 95% CI 0.53 to 1.23, 5 studies, low quality of evidence), reintubation (RR 0.92, 95% CI 0.66 to 1.26, 7 studies, low quality evidence), ICU and long-term weaning unit (LWU) length of stay (MD -7.08 days, 95% CI -16.26 to 2.1, 2 studies, low quality of evidence) and pneumonia (RR 0.67, 95% CI 0.08 to 5.85, 2 studies, low quality of evidence). PS was significantly superior to the TT for successful SBTs (RR 1.09, 95% CI 1.02 to 1.17, 4 studies, moderate quality of evidence). Four studies reported on weaning duration, however we were unable to combined the study data because of differences in how the studies presented their data. One study was at high risk of other bias and four studies were at high risk for detection bias. Three studies reported that the weaning duration was shorter with PS, and in one study the duration was shorter in patients with a TT. To date, we have found evidence of generally low quality from studies comparing pressure support ventilation (PSV) and with a T-tube. The effects on weaning success, ICU mortality, reintubation, ICU and LWU length of stay, and pneumonia were imprecise. However, PSV was more effective than a T-tube for successful spontaneous breathing trials (SBTs) among patients with simple weaning. Based on the findings of single trials, three studies presented a shorter weaning duration in the group undergoing PS SBT, however a fourth study found a shorter weaning duration with a T-tube.


Transforming growth factor Beta 1 stimulates profibrotic activities of luteal fibroblasts in cows.
Luteolysis is characterized by angioregression, luteal cell apoptosis, and remodeling of the extracellular matrix characterized by deposition of collagen 1. Transforming growth factor beta 1 (TGFB1) is a potent mediator of wound healing and fibrotic processes through stimulation of the synthesis of extracellular matrix components. We hypothesized that TGFB1 stimulates profibrotic activities of luteal fibroblasts. We examined the actions of TGFB1 on luteal fibroblast proliferation, extracellular matrix production, floating gel contraction, and chemotaxis. Fibroblasts were isolated from the bovine corpus luteum. Western blot analysis showed that luteal fibroblasts expressed collagen 1 and prolyl 4-hydroxylase but did not express markers of endothelial or steroidogenic cells. Treatment of fibroblasts with TGFB1 stimulated the phosphorylation of SMAD2 and SMAD3. [(3)H]thymidine incorporation studies showed that TGFB1 caused concentration-dependent reductions in DNA synthesis in luteal fibroblasts and significantly (P < 0.05) reduced the proliferative effect of FGF2 and fetal calf serum. However, TGFB1 did not reduce the viability of luteal fibroblasts. Treatment of luteal fibroblasts with TGFB1 induced the expression of laminin, collagen 1, and matrix metalloproteinase 1 as determined by Western blot analysis and gelatin zymography of conditioned medium. TGFB1 increased the chemotaxis of luteal fibroblasts toward fibronectin in a transwell system. Furthermore, TGFB1 increased the fibroblast-mediated contraction of floating bovine collagen 1 gels. These results suggest that TGFB1 contributes to the structural regression of the corpus luteum by stimulating luteal fibroblasts to remodel and contract the extracellular matrix.


Current Updates on the Management of AL Amyloidosis.
Systemic immunoglobulin light chain (AL) amyloidosis is a rare but fatal disease. It results from clonal proliferation of plasma cells with excessive production of insoluble misfolded proteins that aggregate in the extracellular matrix, causing damage to the normal architecture and function of various organs. For decades, treatment for AL amyloidosis was based mainly on therapeutic agents previously studied for its more common counterpart, multiple myeloma. As the prevalence and incidence of AL amyloidosis have increased, ongoing research has been conducted with treatments typically used in myeloma with varying success. In this review, we focus on current treatment strategies and updates to clinical guidelines and therapeutics for AL amyloidosis.


Relationship between radiographic evidence of tracheobronchial lymph node enlargement and definitive or presumptive diagnosis.
Tracheobronchial lymphadenomegaly is commonly associated with lymphosarcoma and disseminated mycotic infection. Available data also suggest other pathologic causes of enlarged tracheobronchial lymph nodes. Our objective was to establish the distribution and prevalence of diseases that cause radiographically evident tracheobronchial lymphadenomegaly in a large population of dogs. Patients were divided into groups based on the methods of diagnoses with 25 having confirmed diagnoses and 85 with presumptive diagnoses. Of the 110 dogs in the study, 92 (84%) had neoplasia and 18 (16%) had infectious diseases. Infections were attributed to Coccidioides (12, 67%), Aspergillus (3, 17%), and 1 each (6%) to Nocardia, Penicillium, and Mycobacteriosis. Tumors were characterized as lymphoma (66, 60%) or nonlymphoid (26, 23.6%). Nonlymphomas in Group 1 included histiocytic sarcoma complex (16%), carcinoma (12%), adenocarcinoma (8%), osteosarcoma (8%), chemodectoma (4%), ganglioneuroblastoma (4%), and neuroendocrine (4%). The number of dogs with tracheobronchial lymphadenomegaly scores 1, 2, 3, 4, or 5 (with 5 being the greatest) was 8 (7%), 15 (14%), 30 (27%), 15 (14%), and 44 (38%), respectively. The results suggest that in addition to diagnoses of lymphoma and fungal infections, other neoplasms and in particular histiocytic sarcoma and metastatic adenocarcinoma, should be considered when tracheobronchial lymphadenomegaly is identified radiographically in dogs. When comparing the degree of tracheobronchial lymphadenopathy by disease category, there was no significant affiliation (P = 0.33).


Central sensitisation in primary Sjögren Syndrome and its effect on sleep quality.
The aim of the present study is to evaluate the presence and frequency of central sensitisation (CS) in primary Sjögren Syndrome (pSS) and to determine the effect of CS on sleep quality. In this cross-sectional study, 50 patients diagnosed with pSS between the ages of 18 and 75 were included. The healthy control group was composed of 43 healthcare workers. Each participant underwent a physical examination, and demographic data and the medications they used were recorded. Central sensitisation inventory and Pittsburgh Sleep Quality Index questionnaires were filled in to garner data on CS and sleep quality, respectively, from all participants. While central sensitisation inventory >40 was detected in 74% of pSS patients, it was 25.6% in healthy controls, and there is a statistically significant difference between the groups (p < .05). A correlation analysis of the central sensitisation inventory and Pittsburgh Sleep Quality Index values of all participants revealed a statistically significant correlation between all parameters other than the duration of sleep (p < .05). CS was found to have a negative effect on sleep quality in patients with pSS. We suggest that the cause of widespread pain seen in patients with pSS as the possible development of CS should be considered.


Interleukin-27 Enforces Regulatory T Cell Functions to Prevent Graft-versus-Host Disease.
Graft-versus-host disease (GvHD) remains a significant complication of allogeneic hematopoietic cell transplantation (HCT), associated with significant morbidity and mortality. GvHD is characterized by dysregulated immune responses and resulting tissue damage of target organs. Recent investigations have focused on Foxp3+ regulatory T cells (Tregs) as a therapeutic tool, based on its regulatory functions in GvHD pathogenesis and their instrumental role in mitigating GvHD severity while preserving graft-versus-leukemia (GvL) activity. There are several challenges to its clinical application, including their paucity, impaired suppressive activity, and instability in vivo. Herein, we report that IL-27 pre-stimulation enhances suppressive functions of both mouse and human Tregs. In a complete MHC mismatched murine bone marrow transplant model, IL-27 pre-stimulated polyclonal iTregs diminish acute (a)GvHD lethality, while preserving the GvL effect. Allo-antigen specificity further improves suppressive functions when combined with IL-27 pre-stimulation. In a xenogeneic (human to mouse) GvHD model, IL-27 pre-stimulated human iTregs are superior in protecting recipients from GvHD. Lastly, we compared gene expression profiles of circulating Tregs isolated from HCT recipients with and without aGvHD and found that Tregs from aGvHD patients express distinct gene signatures enriched in immune activation and inflammation. Therefore, these results highlight a novel function of IL-27 in enforcing Treg functions to prevent aGvHD mediated lethality, proposing the hypothesis that dysregulated Treg functions may account for the potential mechanisms underlying GvHD development.


[History from neuropsychology to cognitive neurosciences in Argentina].
The first step from the neuropsychology in Argentina was in 1883 with the thesis of Antonio Piñeiro about the brain localization of the language and vision disorders, only few years after Broca. The aim of this work has been to describe the development of the neuropsychology in Argentina and its relation with the psychology, neurology and psychiatry. The first period was into the neurology with its French school in?uence. In 1907, Jose Ingeniero published in French his book about "amusia", Cristofredo Jakob the "folia neurobiologica" where he described the organization of the human brain, Vicente Dimitri in 1933 his book "aphasia" and Bernardo de Quiros in 1959 his works about dyslexia. The psychiatry at the hospices with the German influence from Jakob developed to the modern neuropsychiatry with Juan Carlos Goldar. The argentine school of psychology by the holism and the psychoanalysis influence do not accept the neuropsychology until 1960 where was included at the school of psychology from the university of Buenos Aires (UBA) with the first linguistics works of Juan Azcoaga. At the 80, began the North American influence of the neurology with authors like Carlos Mangone (dementia), Ramon Leiguarda (apraxia), Sergio Starkstein (depression and apathy) and Ricardo Allegri (memory and Alzheimer). In 1982 the Argentine Neuropsychological Society was founded and in 1987 was the working group of dementia from the Argentine Neurological Society. At this moment, Aldo Ferreres organized the chair of neuropsychology at the school of psychology (UBA). Nowadays, the growing as discipline is in context of the psychology, neurology and psychiatry in the way of the recent cognitive neurosciences.


Medical end-of-life decision-making in a small resource-poor Caribbean country: a mortality follow-back study of home deaths.
In resource-poor countries, including in Latin American and the Caribbean, empirical information about the characteristics and incidence of medical end-of-life decisions (MELDs)-withholding or withdrawing potentially life-prolonging medical treatments-is largely absent. The aim was to describe the incidence and decision-making characteristics of MELDs taken prior to the death of people who died at home in Trinidad and Tobago (T&T). A mortality follow-back study was used where a representative sample of deaths occurring at home in 2018 was drawn from death certificates at the national death registry. The general practitioners who certified the deaths were sent a questionnaire. The sample consisted of 309 adult deaths and the response rate was 31% (N=96). Physicians were: mostly male (79.2%), practiced medicine for more than twenty-years (63.5%), had no formal palliative care training (69.8%). Non-sudden deaths represented 76% (N=73), of these, medications to alleviate pain and symptoms in the last 7 days of life were administered in 65.8%, including opioids 21%. Potentially life-prolonging treatments were withheld in 9.6% but none withdrawn. No physician/patient discussions about various end-of-life treatment options occurred in 61.6%. Compared to physicians with no formal training in palliative care, those with training more often: prescribed or administered opioids in the last 7 days of life (35.7% vs. 11.1%, P=0.01), had discussions with patients about end-of-life treatment options (60.7% vs. 24.4%, P=0.002), and discussed medication use to alleviate pain and other symptoms with patients (50% vs. 17.8%, P=0.004). Differences in the care and treatment general practitioners provided to their patients could be associated with them having been formally trained in palliative care. The necessary support to further develop palliative care in T&T is needed.


Lysosomal proteomics and disease.
A recent trend in proteomic studies has been to analyze macromolecular complexes such as subcellular organelles instead of complete cells or tissues. This "divide and conquer" approach circumvents some of the formidable problems associated with whole proteome analyses and allows focus on a subset of proteins that may be involved in a particular process or disease of interest. One organelle that has been the focus of considerable attention in proteomic studies is the lysosome, an acidic, membrane-delimited compartment that plays an essential role in the degradation and recycling of biological macromolecules. Lysosomal proteomics have been driven in part by the well-established involvement of this organelle in numerous human diseases, but also by the availability of approaches to selectively visualize and/or isolate subsets of lysosomal proteins. In terms of clinical application, proteomic studies of the lysosome have led to the identification of gene defects in three human hereditary diseases. This review summarizes past progress, current limitations and future directions in the field of lysosomal proteomics.


Active surveillance in small cytological indeterminate thyroid nodules: a call to common sense?
To describe the clinical characteristics and outcomes of patients with cytologically Bethesda IV category (B IV) thyroid nodules who opted for active surveillance. We prospectively evaluated 155 patients with a single thyroid nodule classified as B IV. Immediate molecular testing and/or thyroid surgery was offered, except when the patient (i) could not afford molecular testing/rejected the surgery, (ii) had a high surgical risk, (iii) had other disorders/comorbidities which needed to be addressed with higher priority, and (iv) had undetectable serum calcitonin levels, in whom active surveillance (AS) was performed. From 155 patients, only two patients could afford molecular testing; 84% (n = 130) underwent immediate thyroid surgery: lobectomy was performed in only 8% (n = 10). AS was the initial management for 15% (n = 23) of the patients. The frequency of tumor enlargement was 14% (n = 3), after a median of 42 months (range, 7-72) of follow-up, without any evidence of lymph node or clinical distant metastases development. Deferred surgery was performed in 4 patients (17%) after a median of 24 months (range, 12-48) of AS. Follicular adenoma was diagnosed in three and a follicular variant of papillary thyroid carcinoma in one patient, all of them without evidence of disease after 12 months of follow-up. Despite current guidelines does not support AS for indeterminate Bethesda IV nodules, our findings showed that most of these patients had excellent outcomes, in a setting where lobectomy was not the preference and the access to molecular testing was limited. Probably AS could be a valid alternative in these low-risk tumors in selected patients.


Location and longing: the nicotine craving experience in virtual reality.
Considerable research suggests that cigarette craving is complex, with psychological, emotional, cognitive, and behavioral aspects that are inadequately captured by typical craving assessments that focus on level of severity. That is, the experience of craving, for cigarette smokers, remains poorly understood. This study immersed smokers in different virtual reality (VR) scenarios (with and without cigarette cues present), collected detailed craving assessments, and analyzed the data using a multidimensional analytic approach. Non-treatment-seeking, nicotine dependent smokers (N=22) experienced two different virtual reality scenarios, one with cigarette cues and one without, and rated 24 descriptors related to craving. Multidimensional scaling (MDS) models demonstrate that smokers' experience of craving is qualitatively, structurally different under VR smoking cue conditions versus neutral conditions. This finding sheds new light on the complexity of craving as well as implications for its measurement.


Choledochal cysts in adults.
Choledochal cyst is rarely diagnosed in adulthood. When complicated by biliary tract malignancy, the disease has a distinct presentation and carries a dismal prognosis despite radical surgical resection. Retrospective study. Tertiary referral center. A retrospective study was performed on 30 adult patients who presented with choledochal cyst from January 1, 1989, to December 31, 2000. The clinical presentation, management, and outcome of patients with and without biliary tract malignancy. Nine patients (30%) had biliary tract malignancy complicating choledochal cyst (group A). Compared with 21 patients without malignancy (group B), group A patients had a significantly higher incidence of previous internal drainage operations for choledochal cyst (P =.049) and presentation with cholangitis (P =.03). Four patients in group A underwent pancreaticoduodenectomy and 3 received a palliative biliary drainage operation. The overall median survival of patients in group A was 12 months. Complete excision of choledochal cyst and Roux-en-Y hepaticojejunostomy were performed for all patients in group B, among whom 2 underwent concomitant hemihepatectomy. The operative morbidity and mortality were 14% and 0%, respectively, and there were no long-term complications with a median follow-up of 66 months. Biliary tract malignancy complicating choledochal cyst in adults should be suspected in patients with a history of internal drainage of choledochal cyst and presentation with cholangitis. Complete excision of choledochal cyst with Roux-en-Y hepaticojejunostomy is the treatment of choice for patients without malignancy and can be performed with low operative morbidity and absence of long-term complications in adult patients.


Human immunodeficiency virus-associated polymyositis: a longitudinal study of outcome.
To determine the clinical course and optimum treatment of human immunodeficiency virus (HIV)-associated myositis. Sixty-four patients attending a county outpatient HIV/acquired immunodeficiency syndrome facility were referred for the presence of elevated creatine kinase (CK) levels or muscle weakness. Patients underwent neurologic and rheumatologic evaluation, electromyography, and muscle biopsy after exclusion for recreational drug or alcohol use, metabolic/endocrine disorders, zidovudine therapy, and other infections. Thirteen patients (20%) had biopsy-proven myositis. The median duration of HIV infection prior to diagnosis of myositis was 4.3 years (range 0-11 years). Six patients had concomitant diffuse infiltrative lymphocytosis syndrome. There was no correlation of severity of weakness, stage of HIV infection, or retroviral treatment with the CK level at diagnosis. Eight patients received prednisone (60 mg/day) with 5 attaining complete resolution of myositis. The remaining 3 patients received immunosuppressive therapy (azathioprine or methotrexate and intravenous immunoglobulin) and had normalization of strength and CK. Four patients had spontaneous resolution of their myositis without treatment. HIV-associated myositis occurs at any stage of HIV infection, has a relatively good prognosis, responds well to immunosuppressive therapy, and has little evidence of adverse outcome on the HIV infection.


Clinical Evaluation and Management of Narcolepsy in Children and Adolescents.
While sleepiness is common among children, and particularly adolescents, profound sleepiness in the setting of apparently adequate sleep should prompt consideration of a central disorder of hypersomnolence. These disorders, which include narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome, and others, are likely underrecognized in the pediatric population. Narcolepsy in particular should be of interest to child neurologists as the unique signs and symptoms of this disease often prompt evaluation in pediatric neurology clinics. While sleepiness may appear to be a straightforward complaint, its evaluation requires a nuanced approach. Cataplexy, a hallmark of narcolepsy, can be confused for other neurologic conditions, though understanding its various manifestations makes it readily identifiable. Clinicians should be aware of these symptoms, as delay in diagnosis and misdiagnosis are common in childhood narcolepsy. While treatment options have been limited in the past, many new therapeutic options have become available and can result in significant improvement in symptoms. Given the age at presentation, paroxysmal and chronic features, diagnostic modalities, and available treatment options, the field of child neurology is well equipped to see patients with narcolepsy. In this review, I will focus on the presentation, evaluation, and management of pediatric patients with narcolepsy.


Hirano bodies differentially modulate cell death induced by tau and the amyloid precursor protein intracellular domain.
Hirano bodies are actin-rich paracrystalline inclusions found in brains of patients with Alzheimer's disease (AD), frontotemporal dementia (FTD), and in normal aged individuals. Although studies of post-mortem brain tissue provide clues of etiology, the physiological function of Hirano bodies remains unknown. A cell culture model was utilized to study the interactions of mutant tau proteins, model Hirano bodies, and GSK3β in human astrocytoma cells. Most tau variants showed co-localization with model Hirano bodies. Cosedimentation assays revealed this interaction may be direct, as recombinant purified forms of tau are all capable of binding F-actin. Model Hirano bodies had no effect or enhanced cell death induced by tau in the absence of amyloid precursor protein intracellular domain (AICD). In the presence of AICD and tau, synergistic cell death was observed in most cases, and model Hirano bodies decreased this synergistic cell death, except for forms of tau that caused significant cell death in the presence of Hirano bodies only. A role for the kinase GSK3β is suggested by the finding that a dominant negative form of GSK3β reduces this synergistic cell death. A subset of Hirano bodies in brain tissue of both Alzheimer's disease and normal aged individuals was found to contain tau, with some Hirano bodies in Alzheimer's disease brains containing hyperphosphorylated tau. The results demonstrate a complex interaction between tau and AICD involving activation of GSK3β in promoting cell death, and the ability of Hirano bodies to modulate this process.


Coconuts and curtain cakes: The production of wh-questions in ASD.
Children with autism spectrum disorders (ASD) have been found to exhibit difficulties in wh-question production. It is unclear whether these difficulties are pragmatic or syntactic in nature. The current study used a question elicitation task to assess the production of subject and object wh-questions of children with ASD in two different languages (Hebrew and French) wherein the syntactic structure of wh-questions is different, a fact that may contribute to better understanding of the underlying deficits affecting wh-question production. Crucially, beyond the general correct/error rate we also performed an in-depth analysis of error types, comparing syntactic to pragmatic errors and comparing the distribution of errors in the ASD group to that of children with typical development (TD) and children with Developmental Language Disorder (DLD). Correct production rates were found to be similar for the ASD and DLD groups, but error analysis revealed important differences between the ASD groups in the two languages and the DLD group. The Hebrew- and French ASD groups were found to produce pragmatic errors, which were not found in children with DLD. The pragmatic errors were similar in the two ASD groups. Syntactic errors were affected by the structure of each language. Our results have shown that although the two ASD groups come from different countries and speak different languages, the correct production rates and more importantly, the error types were very similar in the two ASD groups, and very different compared to TD children and children with DLD.Implications: Our results highlight the importance of creating research tasks that test different linguistic functions independently and strengthen the need for conducting fine-grained error analysis to differentiate between groups and gain insights into the deficits underlying each of them.


Phycicoccus ginsenosidimutans sp. nov., isolated from soil of a ginseng field.
A Gram-positive, non-motile, non-spore-forming, aerobic, coccoid-shaped bacterium, designated BXN5-13(T), was isolated from the soil of a ginseng field from Baekdu Mountain in Jilin district, China. Strain BXN5-13(T) grew optimally at 30 °C and pH 6.5-7.5 with 0-2 % (w/v) NaCl. Strain BXN5-13(T) had β-glucosidase activity that was connected with ginsenoside-converting ability, so that it was able to convert ginsenoside Rb(1) to ginsenoside F2. On the basis of 16S rRNA gene sequence analysis, the closest phylogenetic relatives of strain BXN5-13(T) were Phycicoccus aerophilus 5516T-20(T) (98.4 % 16S rRNA gene sequence similarity), P. bigeumensis MSL-03(T) (98.3 %), P. dokdonensis DS-8(T) (97.9 %) and P. jejuensis KSW2-15(T) (96.9 %). Lower sequence similarity (<97.0 %) was found with the type strains of other recognized species of the family Intrasporangiaceae. The predominant quinone was MK-8(H₄). The major fatty acids (>10 %) were iso-C₁₅:₀, C₁₇:₀, anteiso-C₁₅:₀ and iso-C₁₆:₀. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol. The cell-wall peptidoglycan contained meso-diaminopimelic acid. The chemotaxonomic data and the high genomic DNA G+C content of strain BXN5-13(T) (70.8l %) supported its affiliation with the genus Phycicoccus. DNA-DNA relatedness between strain BXN5-13(T) and its closest phylogenetic neighbours was below 16 %. Strain BXN5-13(T) represents a novel species within the genus Phycicoccus, for which the name Phycicoccus ginsenosidimutans sp. nov. is proposed. The type strain is BXN5-13(T) (=KCTC 19419(T)=DSM 21006(T)=LMG 24462(T)).


Trafficking pathways of Cx49-GFP in living mammalian cells.
In the present study we examined the trafficking pathways of connexin49 (Cx49) fused to green fluorescent protein (GFP) in polar and non-polar cell lines. The Cx49 gene was isolated from ovine lens by RT-PCR. Cx49 cDNA was fused to GFP and the hybrid cDNA was transfected into several cell lines. After transfection of Cx49-GFP cDNA into HeLa cells, it was shown using the double whole-cell patch-clamp technique that the expressed fusion protein was still able to form conducting gap junction channels. Synthesis, assembly, and turnover of the Cx49-GFP hybrid protein were investigated using a pulse-chase protocol. A major 78-kDa protein band corresponding to Cx49-GFP could be detected with a turnover of 16-20 h and a half-life time of 10 h. The trafficking pathways of Cx49-GFP were monitored by confocal laser microscopy. Fusion proteins were localized in subcellular compartments, including the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment, the Golgi apparatus, and the trans-Golgi network, as well as vesicles traveling towards the plasma membrane. Time-dependent sequential localization of Cx49-GFP in the ER and then the Golgi apparatus supports the notion of a slow turnover of Cx49-GFP compared to other connexins analyzed so far. Gap junction plaques resembling the usual punctuate distribution pattern could be demonstrated for COS-1 and MDCK cells. Basolateral distribution of Cx49-GFP was observed in polar MDCK cells, indicating specific sorting behavior of Cx49 in polarized cells. Together, this report describes the first characterization of biosynthesis and trafficking of lens Cx49.


Hormonal, metabolic, and cardiorespiratory responses of young and adult athletes to a single session of high-intensity cycle exercise.
This study aimed to determine the effects of a single high-intensity interval training (HIIT) session on salivary cortisol (SC) levels, physiological responses, and performance in trained boys and men. Twenty-three boys (11.5 ± 0.8 years) and 25 men (29.7 ± 4.6 years) performed HIIT (4 consecutive Wingate Anaerobic Tests). SC in boys and men increased after HIIT from 5.55 ± 3.3 nmol/l to 15.13 ± 9.7 nmol/l (+173%) and from 7.07 ± 4.7 nmol/l to 19.19 ± 12.7 nmol/l (+171%), respectively (p < .01). Pretest SC as well as posttest changes were comparable in both groups (both p < .01). Peak blood lactate concentration was significantly lower in boys (12.6 ± 3.5 mmol/l) than in men (16.3 ± 3.1 mmol/l; p < .01). Throughout the HIIT, mean heart rates in boys were higher (p < .001) but relative peak oxygen uptake (ml·min-1·kg-1; p < .05) and performance were lower (p < .001) in boys than in men. HIIT in young athletes is associated with a higher activation of the hormonal stress axis than other types of exercise regimes as described in the literature. This study is the first to show a pronounced SC increase to HIIT in trained boys accompanied by elevated levels of blood lactate concentrations and heart rate suggesting a high cardio-respiratory, metabolic, and hormonal response to HIIT in 11-year-old boys.


Additional organ resection combined with pancreaticoduodenectomy does not increase postoperative morbidity and mortality.
The mortality associated with pancreaticoduodenectomy (PD) has decreased substantially in recent times, but high morbidity continues to be a significant problem. With reductions in mortality, there is increasing willingness to combine organ resections with PD when indicated. There is, however, a paucity of information regarding the morbidity and mortality of multivisceral resection (MVR) that involves pancreaticoduodenectomy (MVR-PD). Patients undergoing PD between January 2002 and November 2007 by a single surgeon were reviewed and perioperative outcomes determined. Those treated by PD alone were compared to those undergoing MVR-PD. There were 105 patients overall who underwent PD during the study period, with MVR-PD performed in 19 patients. Twelve (63%) patients required PD combined with right colectomy, two (11%) underwent PD combined with right nephrectomy, two (11%) required liver resection with PD, and the remaining three (16%) had various combinations of kidney, colon, adrenal and small bowel resection in addition to PD. In both groups, the main indication for surgery was pancreatic cancer; however, there were proportionally more patients in the MVR-PD group with gastrointestinal stromal tumors (two (11%) patients), sarcomas (two (11%) patients) and metastases to the periampullary region (three (16%) patients). The overall complication rate in this study was 60%. Delayed gastric emptying (39%) and pancreatic fistula (16%) were the most common complications. There was no significant difference in complications between the two groups. A non pylorus-preserving PD was more commonly performed in cases of MVR-PD (53% vs 28%; p = 0.007), operating times were longer (9.5 vs 8 h; p = 0.002), and surgical intensive care unit stay was greater (2 vs 1 days; p < 0.001). The overall median length of hospital stay (7 days) and readmission rate were similar between the groups. MVR-PD can be performed without significant added morbidity compared to PD alone. The main indication for MVR-PD is locally advanced pancreatic cancer requiring PD combined with right hemicolectomy.


Gigantol exerts anti-lung cancer activity by inducing ferroptosis via SLC7A11-GPX4 axis.
Gigantol, a naturally occurring dibenzyl compound derived from various orchid species within the Dendrobium genus, exhibits notable pharmacological activity. We found that gigantol has significant anti-lung cancer properties, both in vitro and in vivo, which it exerts through the induction of ferroptosis. Furthermore, we found gigantol's specific interaction with the subunit solute carrier family 7 member 11 (SLC7A11) within the cystine/glutamate antiporter system (system Xc-), leading to the inhibition of glutathione (GSH) synthesis. This, in turn, disrupts redox homeostasis. Additionally, gigantol hinders the uptake of extracellular cystine via lung cancer cells, resulting in reduced cellular levels of cysteine, a vital precursor in GSH synthesis. This reduction, in turn, leads to an increase in the levels of glutamate. Simultaneously, our study reveals that the decrease in GSH significantly inhibits the activity of glutathione peroxidase 4 (GPX4), a key enzyme within the antioxidant system. Remarkably, N-acetylcysteine, a cystine precursor, effectively reverses gigantol-induced ferroptosis in lung cancer cells. This provides further confirmation that the anti-lung cancer mechanism of gigantol is to induce ferroptosis of lung cancer cells by targeting the SLC7A11-GPX4 signaling axis. In conclusion, our study underscores gigantol's potential as a promising candidate drug for the treatment of patients with lung cancer in clinical practice.


4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.
Functional neuroimaging, using genetically-encoded Ca2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.


Comparative analysis of detoxification enzymes in Acyrthosiphon pisum and Myzus persicae.
Herbivorous insects use detoxification enzymes, including cytochrome P450 monooxygenases, glutathione S-transferases, and carboxy/cholinesterases, to metabolize otherwise deleterious plant secondary metabolites. Whereas Acyrthosiphon pisum (pea aphid) feeds almost exclusively from the Fabaceae, Myzus persicae (green peach aphid) feeds from hundreds of species in more than forty plant families. Therefore, M. persicae as a species would be exposed to a greater diversity of plant secondary metabolites than A. pisum, and has been predicted to require a larger complement of detoxification enzymes. A comparison of M. persicae cDNA and A. pisum genomic sequences is partially consistent with this hypothesis. There is evidence of at least 40% more cytochrome P450 genes in M. persicae than in A. pisum. In contrast, no major differences were found between the two species in the numbers of glutathione S-transferases, and carboxy/cholinesterases. However, given the incomplete M. persicae cDNA data set, the number of identified detoxification genes in this species is likely to be an underestimate.


Exploration during early life: distribution, habitat and orientation preferences in juvenile king penguins.
The early life of marine apex predators is poorly known, particularly for diving species. The orientation and foraging skills are presumably less developed in juveniles than in adults, especially during their first year at sea when juveniles might disperse further than adults. Over two years of monitoring, we tracked the movements of 17 juvenile king penguins (Aptenodytes patagonicus, ~ 1 year old) using satellite relay tags from Crozet Archipelago (Southern Indian Ocean), starting when birds left their natal colony for the first time. For comparison we also tagged 6 non-breeding adults, which at that stage, similar to juveniles, are unhampered by reproductive constraints and might roam further than breeders. We used a combination of cluster analysis and habitat modelling to investigate and compare the movement patterns and habitat use of experienced (non-breeding adults) and non-experienced (juveniles) individuals. While juvenile penguins and non-breeding adults followed similar routes, the movements by adults started later in the season and ranged over a considerably smaller area than juveniles. Net squared displacement analysis revealed that both groups did not move to a specific wintering area. Changes in direction of juveniles in respect to their departure island were similar and synchronous for both years. Habitat models revealed that foraging behaviour was affected by environmental variables such as wind or current speeds, sea surface temperature, or oceanic productivity, for both stages. Analysis of tracks revealed that birds moved predominately perpendicular or against the main direction of the Antarctic Circumpolar Current and the prevailing wind during austral summer (juveniles only) and autumn (juveniles and non-breeding adults). However, both juveniles and adults were more likely to move against the prevailing winds if productivity increased along their trajectories. The exceptional duration of our tracking study provided unprecedented insights into the distribution, habitat preferences and orientation of two poorly known life history stages of an expert avian diver. Our study suggests that juveniles might use both innate and learnt skills to reach profitable foraging areas during their first year at sea, which is critical in long-lived species.


The essential role of YAP in ERα36-mediated proliferation and the epithelial-mesenchymal transition in MCF-7 breast cancer cells.
Purpose: Most breast cancers are hormone-receptor-positive, and thus the first-line therapy for them is an anti-estrogen medication such as tamoxifen. If metastasis occurs or resistance to tamoxifen develops, the 5-year survival rates for breast cancer patients significantly decrease. Hence, a better understanding of the molecular mechanisms that contribute to breast cancer aggressiveness is of great importance. ERα36 is an estrogen receptor variant that is known to be upregulated in breast cancer patients receiving tamoxifen treatment or in triple-negative breast cancer cells. However, the specific molecular mechanism underlying ERα36-induced tamoxifen-resistance is not yet fully understood. Methods: ERα36-overexpressing MCF-7 cells were constructed by either plasmid transfection using ERα36 vector or retroviral infection using ERα36-V5-His vector. Target-gene expression was assessed by Western blot analysis and real-time PCR, and YAP activation was evaluated by luciferase assays and immunofluorescence. Cell proliferation and formation of three-dimensional spheroids were evaluated using the IncuCyte S3 Live Cell Analysis System. Results: We found that the expression patterns of Hippo signaling-related genes were significantly changed in ERα36-overexpressing MCF-7 cells compared to MCF-7 cells, which were also similarly observed in tamoxifen-resistant MCF-7 cells. Specifically, the protein expression level and activity of YAP, the core downstream protein of the Hippo pathway, were significantly increased in ERα36-overexpressing MCF-7 cells compared with MCF-7 cells. The aggressive phenotypes acquired by ERα36 overexpression in MCF-7 cells were destroyed by YAP knockout. On this basis, we propose that ERα36 regulates YAP activity by a new mechanism involving Src kinase. Conclusion: Our results suggest that YAP targeting may be a new therapeutic approach to the treatment of advanced breast cancers overexpressing ERα36.


Personalization of Visual Scene Displays: Preliminary Investigations of Adults with Aphasia, Typical Females across the Age-Span, and Young Adult Males and Females.
Visual scene displays (VSDs) are becoming an increasingly popular method of message representation within augmentative and alternative communication (AAC) supports; however, design factors can influence the effectiveness of these images as communication supports. One issue that has come to light in recent years is the fact that selecting personalized VSDs, which depict the person with complex communication needs or an individual with whom they are familiar, are preferred over generic VSDs, which depict unfamiliar individuals. Although personalization is likely an important factor in the usability of VSDs, these images may be difficult for clinicians to obtain. As such, compromises must be identified. The purpose of this study was to explore the effects of controlling personal relevance factors (i.e., age and gender of the people depicted in generic VSDs) on the image preference patterns of adults with and without aphasia. Results from three very preliminary study summaries indicate that gender and age are both mitigating factors in image preference, as males tended to indicate preference for VSDs containing males over those containing females. In addition, females tended to indicate preference for females of a similar age depicted in VSDs.


Coupled optical microcavities: an enhanced refractometric sensing configuration.
We theoretically investigate the application of coupled optical microcavities as refractive index sensors. Coupled microcavities support a very sharp asymmetrical Fano resonance, which gives rise to faster changes in output transmission than the changes from a single cavity. With the output transmission at a fixed wavelength that varies much faster than it does in a single-cavity resonance, the result is enhanced sensitivity of the device to the changes in refractive index. In addition, it is observed that both thermal and optical Kerr effects can be utilized to improve the sensitivity.


A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region.
DGS and VCFS, haploinsufficiencies characterized by multiple craniofacial and cardiac abnormalities, are associated with a microdeletion of chromosome 22q11.2. Here we document synteny between a 150-kb region on mouse chromosome 16 and the most commonly deleted portion of 22q11.2. Seven genes, all of which are transcribed in the early mouse embryo, have been identified. Of particular interest are two serine/threonine kinase genes and a novel goosecoid-like homeobox gene (Gscl). Comparative sequence analysis of a 38-kb segment reveals similarities in gene content, order, exon composition, and transcriptional direction. Therefore, if deletion of these genes results in DGS/VCFS in humans, then haploinsufficiencies involving this region of chromosome 16 should recapitulate the developmental field defects characteristic of this syndrome.


Hepatitis C virus micro-elimination: Where do we stand?
Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviral treatments, has been promoted by the World Health Organization. This achievement is not attainable, however, particularly after the 2020 pandemic of the coronavirus disease 2019. Consequently, the more realistic objective of eliminating HCV from population segments for which targeted strategies of prevention and treatment are easily attained has been promoted in Europe, as a valid alternative. The underlying idea is that micro-elimination will ultimately lead to macro-elimination. The micro-elimination strategy may target different specific populations and at-risk groups. Different settings, including prisons and hospitals, have also been identified as micro-elimination scenarios. In addition, dedicated micro-elimination strategies have been designed that are tailored at the geographical level according to HCV epidemiology and individual country's income. The main elements of a valid and successful micro-elimination project are reliable epidemiological data and active involvement of all the stakeholders. Community involvement represents another essential component for a successful program.


[The criminalization of sexual relations between or with adolescents and its impact on the exercise of their sexual and reproductive rights].
This article analyzes the impact of the decrete 28704, issued in 2006, on the Peruvian society. This Law states that all sexual relations between the age of 14 and an age younger than 18, whether consented or not, shall be considered rape, thus criminalizing adolescent sexuality and making preventive reproductive health services illegal. This decision was made disregarding the legal frameworks which recognize and protect sexual and reproductive rights, the needs of adolescents regarding sexuality, as well as its impact on public health issues. In 2012, this Law was declared unconstitutional. The enforcement of this sentence shall enable the implementation and improvement of public sexual education policies and the access to quality health care. An effort to create more effective laws to protect adolescents from sexual violence must be made.


Feeding cycle alters the biophysics and molecular expression of voltage-gated Na+ currents in rat hippocampal CA1 neurones.
The function of hippocampus as a hub for energy balance is a subject of broad and current interest. This study aims at providing more evidence on this regard by addressing the effects of feeding cycle on the voltage-gated sodium (Na+ ) currents of acutely isolated Wistar rat hippocampal CA1 neurones. Specifically, by applying patch clamp techniques (whole cell voltage clamp and single channel in inside-out patches) we assessed the influence of feeding and fasting conditions on the intrinsic biophysical properties of Na+ currents. Additionally, mass spectrometry and western blotting experiments were used to address the effect of feeding cycle over the Na+ channel population of the rat hippocampus. Na+ currents were recorded in neurones obtained from fed and fasted animals (here termed "fed neurones" and "fasted neurones", respectively). Whole cell Na+ currents of fed neurones, as compared to fasted neurones, showed increased mean maximum current density and a higher "window current" amplitude. We demonstrate that these results are supported by an increased single channel Na+ conductance in fed neurones and, also, by a greater Nav1.2 channel density in plasma membrane-enriched fractions of fed samples (but not in whole hippocampus preparations). These results imply fast variations on the biophysics and molecular expression of Na+ currents of rat hippocampal CA1 neurones, throughout the feeding cycle. Thus, one may expect a differentiated regulation of the intrinsic neuronal excitability, which may account for the role of the hippocampus as a processor of satiety information.


Thermal Properties of Porous Silicon Nanomaterials.
The thermal properties, including the heat capacity, thermal conductivity, effusivity, diffusivity, and phonon density of states of silicon-based nanomaterials are analyzed using a molecular dynamics calculation. These quantities are calculated in more detail for bulk silicon, porous silicon, and a silicon aerocrystal (aerogel), including the passivation of the porous internal surfaces with hydrogen, hydroxide, and oxygen ions. It is found that the heat capacity of these materials increases monotonically by up to 30% with an increase in the area of the porous inner surface and upon its passivation with these ions. This phenomenon is explained by a shift of the phonon density of states of the materials under study to the low-frequency region. In addition, it is shown that the thermal conductivity of the investigated materials depends on the degree of their porosity and can be changed significantly upon the passivation of their inner surface with different ions. It is demonstrated that, in the various simulated types of porous silicon, the thermal conductivity changes by 1-2 orders of magnitude compared with the value for bulk silicon. At the same time, it is found that the nature of the passivation of the internal nanosilicon surfaces affects the thermal conductivity. For example, the passivation of the surfaces with hydrogen does not significantly change this parameter, whereas a passivation with oxygen ions reduces it by a factor of two on average, and passivation with hydroxyl ions increases the thermal conductivity by a factor of 2-3. Similar trends are observed for the thermal effusivities and diffusivities of all the types of nanoporous silicon under passivation, but, in that case, the changes are weaker (by a factor of 1.5-2). The ways of tuning the thermal properties of the new nanostructured materials are outlined, which is important for their application.


Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
Exposure to ultraviolet (UV) light can cause significant damage to mammalian cells and, although the spectrum of damage produced varies with the wavelength of UV, all parts of the UV spectrum are recognised as being detrimental to human health. Characterising the cellular response to different wavelengths of UV therefore remains an important aim so that risks and their moderation can be evaluated, in particular in relation to the initiation of skin cancer. The p53 tumour suppressor protein is central to the cellular response that protects the genome from damage by external agents such as UV, thus reducing the risk of tumorigenesis. In response to a variety of DNA damaging agents including UV light, wild-type p53 plays a role in mediating cell-cycle arrest, facilitating apoptosis and stimulating repair processes, all of which prevent the propagation of potentially mutagenic defects. In this study we examined the induction of p53 protein and its influence on the survival of primary mouse fibroblasts exposed to different wavelengths of UV light. UVC was found to elevate p53 protein and its sequence specific DNA binding capacity. Unexpectedly, UVA treatment failed to induce p53 protein accumulation or sequence specific DNA binding. Despite this, UVA exposure of wild-type cells induced a p53 dependent G1 cell cycle arrest followed by a wave of p53 dependent apoptosis, peaking 12 hours post-insult. Thus, it is demonstrated that the elements of the p53 cellular response evoked by exposure to UV radiation are wavelength dependent. Furthermore, the interrelationship between various endpoints is complex and not easily predictable. This has important implications not only for understanding the mode of action of p53 but also for the use of molecular endpoints in quantifying exposure to different wavelengths of UV in the context of human health protection.


Effect of Calcification Based on Computer-Aided System on CT-Fractional Flow Reserve in Diagnosis of Coronary Artery Lesion.
This study was to analyze the diagnostic value of coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) based on computer-aided diagnosis (CAD) system for coronary lesions and the possible impact of calcification. 80 patients who underwent CCTA and FFR examination in hospital were selected as the subjects. The FFR value of 0.8 was used as the dividing line and divided into the ischemic group (FFR ≤ 0.8) and nonischemic group (FFR > 0.8). The basic data and imaging characteristics of patients were analyzed. The maximum diameter stenosis rate (MDS %), maximum area stenosis rate (MAS %), and napkin ring sign (NRS) in the ischemic group were significantly lower than those in the nonischemic group (P < 0.05). Remodeling index (RI) and eccentric index (EI) compared with the nonischemic group had no significant difference (P > 0.05). The total plaque volume (TPV), total plaque burden (TPB), calcified plaque volume (CPV), lipid plaque volume (LPV), and lipid plaque burden (LPB) in the ischemic group were significantly different from those in the non-ischemic group (P < 0.05). MAS % had the largest area under curve (AUC) for the diagnosis of coronary myocardial ischemia (0.74), followed by MDS % (0.69) and LPV (0.68). CT-FFR had high diagnostic sensitivity, specificity, accuracy, truncation value, and AUC area data for patients in the ischemic group and nonischemic group. The diagnostic sensitivity, specificity, accuracy, cutoff value, and AUC area data of CT-FFR were higher in the ischemic group (89.93%, 92.07%, 95.84%, 60.51%, 0.932) and nonischemic group (93.75%, 90.88%, 96.24%, 58.22%, 0.944), but there were no significant differences between the two groups (P > 0.05). In summary, CT-FFR based on CAD system has high accuracy in evaluating myocardial ischemia caused by coronary artery stenosis, and within a certain range of calcification scores, calcification does not affect the diagnostic accuracy of CT-FFR.


Submillisievert Computed Tomography of the Chest in Contact Investigation for Drug-Resistant Tuberculosis.
Close contacts with infectious tuberculosis (TB) are persons at high risk for developing active disease. We preliminarily introduced submillisievert chest computed tomography (CT) scan (effective dose, 0.19-0.25 millisievert) in a contact investigation of multi-drug resistant (MDR)-TB. Baseline CT scan showed minimal nodules or branching opacities in two of six contacts. A two-month follow-up examination revealed a radiologic progression in contact 1, subsequently having the microbiologic diagnosis of MDR-TB at an asymptomatic early stage, whereas nodules transiently increased after 3 months in contact 2, followed by a decrease after one year. Contact 1 was cured after 1.5-year of anti-MDR-TB treatment. In conclusion, early identification of secondary MDR-TB is feasible with submillisievert chest CT scans in contact investigations of MDR-TB, minimizing of MDR-TB transmission and offering a favorable treatment outcome. This was a clinical trial study and was registered at www.ClinicalTrials.gov (Identifier: NCT02454738).


[Effect of the structural integrity of Na,K-ATPase preparations on the ability of lithium to substitute for sodium in enzyme activation].
The ability of Li+ to substitute for Na+ in activating ouabain-sensitive ATPase of the rat kidney was studied on three kinds of the enzyme preparation: a) crude membrane fraction, b) purified enzyme, c) tissue slices. The preparations were free of endogenous Na+ and K+. The ATPase activity of slices was estimated both biochemically and cytochemically. In slices, the extent of Li+--Na+-isomorphism was about 10-fold higher than that in the purified enzyme. It is concluded that the biochemical procedures involved in the enzyme isolation procedure cause the damage of membranes, thus decreasing Li+-affinity to the Na+-dependent site.


Geminin overexpression induces mammary tumors via suppressing cytokinesis.
Aneuploidy plays an important role in the development of cancer. Here, we uncovered an oncogenic role for geminin in mitotic cells. In addition to chromatin, tyrosine phosphorylated geminin also localizes to centrosome, spindle, cleavage furrow and midbody during mitosis. Geminin binding to Aurora B prevents its binding to INCENP, and thus activation leading to lack of histone H3-(serine 10) phosphorylation, chromosome condensation failure, aborted cytokinesis and the formation of aneuploid, drug resistance cells. Geminin overexpressing human mammary epithelial cells form aneuploid, aggressive tumors in SCID mice. Geminin is overexpressed in more than half of all breast cancers analyzed. The current study reveals that geminin is a genuine oncogene that promotes cytokinesis failure and production of aneuploid, aggressive breast tumors when overexpressed and thus a worthy therapeutic target (oncotarget) for aggressive breast cancer.


(N-sec-Butyl-N-n-propyl-dithio-carbamato-κS,S')triphenyl-tin(IV).
The Sn atom in the title compound, [Sn(C(6)H(5))(3)(C(8)H(16)NS(2))], is penta-coordinated by two S atoms, derived from an asymmetrically coordinating dithio-carbamate ligand, and three ipso-C atoms. The coordination geometry is inter-mediate between square-pyramidal and trigonal-bipyramidal, with a leaning towards the latter. The presence of close intra-molecular C-H⋯S contacts preclude the S atoms from forming significant inter-molecular inter-actions. Rather, mol-ecules are consolid-ated in the crystal structure by C-H⋯π inter-actions.