Dietary high-protein distiller's dried grains with solubles can fully replace soybean meal in diets for meat quails without affecting growth performance.
1. The purpose of this study was to determine the metabolisable energy of high-protein distiller's dried grains with solubles (HP-DDGS) for meat quail (Coturnix coturnix coturnix; Experiment I) and evaluate the effects of dietary levels of HP-DDGS on animal performance, carcase characteristics, meat quality, and organ weights (Experiment II).2. In Experiment 1, 96 meat quail were distributed in a completely randomised design with two treatments (reference or test diet) and six replicates of eight birds. The experimental period consisted of 5 d adaptation, followed by 5 d total excreta collection. The experimental diets consisted of a reference (control) and a test diet formulated with 800 g/kg reference diet and 200 g/kg HP-DDGS.3. In Experiment 2, 612 meat quail were distributed in a completely randomised design fed one of six dietary levels of HP-DDGS (0, 85, 170, 255, 340, or 425 g/kg) as a replacement for soybean meal. At 42 d of age, birds were slaughtered and evaluated for carcase yield, organ weights, and meat quality.4. Apparent metabolisable energy values corrected for nitrogen retention of HP-DDGS were 12.5 and 12.3 MJ/kg for males and females, respectively.5. In the starter phase (1-21 d of age), increasing dietary HP-DDGS levels had a quadratic effect on body weight (BW) (P = 0.020) and body weight gain (BWG) (P = 0.019). The maximum BW and BWG values were estimated to be achieved with 296.0 and 296.2 g/kg dietary HP-DDGS, respectively. Overall (1-42 d of age), increasing dietary HP-DDGS levels in replacement of soybean meal did not affect animal performance, carcase yield, meat quality or organ weight in meat quail.6. It was concluded that dietary HP-DDGS can fully replace soybean meal in meat quail diets without affecting growth performance, carcase yield, meat quality or organ weight.


The kinetics of inorganic phosphate excretion in the acidotic rabbit during intravenous phosphate loading: a pseudo-ruminant model.
The rabbit is a much-used experimental animal in renal tubule physiology studies. Although a monogastric mammal, the rabbit is a known hindgut fermenter. That ruminant species excrete inorganic phosphate (Pi) mainly through the digestive system while non-ruminants eliminate surplus phosphate primarily through the renal system are acknowledged facts. To understand phosphate homeostasis in the acidotic rabbit, anaesthetized animals were infused with hydrochloric acid, after which they underwent intravenous phosphate loading. Biofluids were collected during the infusion process for analysis. Plasma Pi increased (7.9 ± 1.7 mmoles.Litre-1 (N = 5) vs 2.2 ± 0.4 mmoles.Litre-1 (N = 10) pre-infusion, (p < 0.001)), while urinary phosphate excretion was also enhanced (74.4 ± 15.3 from a control value of 4.7 ± 3 µmol.min-1 (N = 9), pre-infusion, p < 0.001)) over an 82.5 minute Pi loading period. However, the fractional excretion of Pi (FePi) only increased from 14.2 ± 5.4% to a maximum of 61.7 ± 19% (N = 5) over the infusion period. Furthermore, the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmPi/GFR) computed to 3.5 mmol.L-1, while a reading of 23.2 µmol.min-1.Kg.0.75 was obtained for the transport maximum for Pi (TmPi). The high reabsorptivity of the rabbit nephrons coupled with possibly a high secretory capacity of the salivary glands for Pi, may constitute a unique physiological mechanism that ensures the rabbit hindgut receives adequate phosphate to regulate caecal pH in favour of the resident metabolically - active microbiota. The handling of Pi by the rabbit is in keeping with the description of this animal as a monogastric, pseudo-ruminant herbivore.


Effects of parasitism and morphology on squirrelpox virus seroprevalence in grey squirrels (Sciurus carolinensis).
Invasive species have been cited as major causes of population extinctions in several animal and plant classes worldwide. The North American grey squirrel (Sciurus carolinensis) has a major detrimental effect on native red squirrel (Sciurus vulgaris) populations across Britain and Ireland, in part because it can be a reservoir host for the deadly squirrelpox virus (SQPV). Whilst various researchers have investigated the epizootiology of SQPV disease in grey squirrels and have modelled the consequent effects on red squirrel populations, less work has examined morphological and physiological characteristics that might make individual grey squirrels more susceptible to contracting SQPV. The current study investigated the putative relationships between morphology, parasitism, and SQPV exposure in grey squirrels. We found geographical, sex, and morphological differences in SQPV seroprevalence. In particular, larger animals, those with wide zygomatic arch widths (ZAW), males with large testes, and individuals with concurrent nematode and/or coccidial infections had an increased seroprevalence of SQPV. In addition, males with larger spleens, particularly those with narrow ZAW, were more likely to be exposed to SQPV. Overall these results show that there is variation in SQPV seroprevalence in grey squirrels and that, consequently, certain individual, or populations of, grey squirrels might be more responsible for transmitting SQPV to native red squirrel populations.


Gene interactions from maternal effects.
Theoretical analyses have demonstrated a potential role for epistasis in many of the most important processes in evolution. These analyses generally assume that an individual's genes map directly to its phenotype and epistasis results from interactions among loci that contribute to the same biochemical or developmental pathways (termed physiological, or within-genotype, epistasis). For many characters, particularly those expressed early in life, an individual's phenotype may also be affected by genes expressed by its parents. The presence of these parental effects allows for interactions between the genes present in the parental and offspring genomes. When the phenotypic effect of a locus in the offspring depends on the alleles possessed by its parents, genotype-by-genotype, or among-genotype, epistasis occurs. The among-genotype epistasis resulting from parental effects may contribute to ruggedness of adaptive landscapes because early mortality often accounts for much of the variance in fitness in populations. To demonstrate how parent-offspring interactions can result in among-genotype epistasis, I use a two-locus model, with one maternal effect locus and one direct effect locus, each with two alleles. Dynamical equations are presented for the two-locus model and are directly contrasted with the dynamical equations derived for a model for physiological epistasis. The relationship between the evolutionary dynamics resulting from these two forms of epistasis is discussed. Three scenarios are presented to illustrate systems in which maternal-offspring, genotype-by-genotype epistasis may occur. The implications of maternal-offspring epistasis for quantitative-trait-loci studies are also discussed.


Accurate analysis of planar optical waveguide devices using higher-order FDTD scheme.
A higher-order finite-difference time-domain (HO-FDTD) numerical method is proposed for the time-domain analysis of planar optical waveguide devices. The anisotropic perfectly matched layer (APML) absorbing boundary condition for the HO-FDTD scheme is implemented and the numerical dispersion of this scheme is studied. The numerical simulations for the parallel-slab directional coupler are presented and the computing results using this scheme are in highly accordance with analytical solutions. Compared with conventional FDTD method, this scheme can save considerable computational resource without sacrificing solution accuracy and especially could be applied in the accurate analysis of optical devices.


Lumboscopic-Assisted Pyeloplasty: A Single-Port, Retroperitoneoscopic Approach for Children with Pelvi-Ureteric Junction Obstruction.
Pelvi-ureteric junction obstruction (PUJO) is one of the most common conditions presenting to a pediatric urologist. As laparoscopic or robotic-assisted pyeloplasty, either transperitoneal or retroperitoneal, involves intracorporeal suturing skills and has a long learning curve, they have not gained popularity among beginners in laparoscopy. We conducted a study to assess the results of a single-port, retroperitoneoscopic approach to renal access, i.e. lumboscopic-assisted pyeloplasty (LAP), by single surgeon at our institute. A retrospective review of all children who underwent LAP from July 2013 to March 2018 was conducted. Patients who presented with PUJO and required surgical treatment were included. A single-port lumboscopy using coaxial telescope was performed in prone position in all patients. The renal pelvis was dissected and retrieved through the port site followed by extracorporeal hand-sewn pyeloplasty over a double-J stent or a nephrostent. The operative time, postoperative pain, surgical complications, duration of hospital stay, follow-up, and cosmesis at 6 months postsurgery were evaluated. A total of 96 children were included (72 males and 24 females), with the age at operation ranging from 3 months to 10 years (mean = 4.9 years). All patients had an uneventful postoperative recovery. Two patients had a superficial wound infection, and one patient was converted to open approach due to excessive bleeding. The average operating time was 80 ± 22.5 min, the median duration of hospital stay was 3 days, and the average scar length at 3 months was 15.6 ± 0.4 mm. Follow-up renogram (diethylenetriamine pentaacetic acid) showed satisfactory postpyeloplasty drainage pattern in 93 children while three showed obstructive drainage curves. LAP can be performed safely with minimal retroperitoneal dissection, excellent cosmetic results, and minimal postoperative pain in children with PUJO. It has a shorter learning curve as compared to laparoscopic pyeloplasty as it involves time tested extracorporeal hand-sewn anastomosis.


Investigational PI3K/AKT/mTOR inhibitors in development for endometrial cancer.
Endometrial cancer (EC) is the most common neoplasm of the female genital tract in developed countries. Despite the progress in early detection and treatment, a significant number of cases of advanced ECs are still diagnosed. These patients have few treatment options and a poor prognosis. Our understanding of EC pathogenesis and progression has been enhanced by recent genomic studies. Among the relevant biological pathways, phosphatidylinositol 3-kinase/AKT (PIK3/AKT)-mammalian target of rapamycin (mTOR) signaling is frequently upregulated in this cancer. This review covers investigational EC therapeutics acting on the PI3K/AKT/mTOR pathway. The authors review the results of clinical studies and highlight ongoing trials. Several new agents are under evaluation for treating patients with metastatic, recurrent, and persistent EC. Clinical trials investigating PI3K/AKT/mTOR inhibitors have yielded controversial results. In the near future, new studies with dual inhibitors or multi-pathways inhibitors as mono or combination therapies with conventional chemotherapy (CT) or other targeted drugs may provide more promising data. Moreover, the evaluation of new serum and histological biomarkers is an attractive strategy for patient selection.


The role of genes involved in neuroplasticity and neurogenesis in the observation of a gene-environment interaction (GxE) in schizophrenia.
Schizophrenia is a multifactorial disease characterized by a high heritability. Several candidate genes have been suggested, with the strongest evidences for genes encoding dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), neuregulin 1 receptor (ERBB4) and disrupted in schizophrenia 1 (DISC1), as well as several neurotrophic factors. These genes are involved in neuronal plasticity and play also a role in adult neurogenesis. Therefore, the genetic basis of schizophrenia could involve different factors more or less specifically required for neuroplasticity, including the synapse maturation, potentiation and plasticity as well as neurogenesis. Following the model of Knudson in tumors, we propose a two-hit hypothesis of schizophrenia. In this model of gene-environment interaction, a variant in a gene related to neurogenesis is transmitted to the descent (first hit), and, secondarily, an environmental factor occurs during the development of the central nervous system (second hit). Both of these vulnerability and trigger factors are probably necessary to generate a deficit in neurogenesis and therefore to cause schizophrenia. The literature supporting this gene x environment hypothesis is reviewed, with emphasis on some molecular pathways, raising the possibility to propose more specific molecular medicine.


CD8+ T cells specific for a malaria cytoplasmic antigen form clusters around infected hepatocytes and are protective at the liver stage of infection.
Following Anopheles mosquito-mediated introduction into a human host, Plasmodium parasites infect hepatocytes and undergo intensive replication. Accumulating evidence indicates that CD8(+) T cells induced by immunization with attenuated Plasmodium sporozoites can confer sterile immunity at the liver stage of infection; however, the mechanisms underlying this protection are not clearly understood. To address this, we generated recombinant Plasmodium berghei ANKA expressing a fusion protein of an ovalbumin epitope and green fluorescent protein in the cytoplasm of the parasite. We have shown that the ovalbumin epitope is presented by infected liver cells in a manner dependent on a transporter associated with antigen processing and becomes a target of specific CD8(+) T cells from the T cell receptor transgenic mouse line OT-I, leading to protection at the liver stage of Plasmodium infection. We visualized the interaction between OT-I cells and infected hepatocytes by intravital imaging using two-photon microscopy. OT-I cells formed clusters around infected hepatocytes, leading to the elimination of the intrahepatic parasites and subsequent formation of large clusters of OT-I cells in the liver. Gamma interferon expressed in CD8(+) T cells was dispensable for this protective response. Additionally, we found that polyclonal ovalbumin-specific memory CD8(+) T cells induced by de novo immunization were able to confer sterile protection, although the threshold frequency of the protection was relatively high. These studies revealed a novel mechanism of specific CD8(+) T cell-mediated protective immunity and demonstrated that proteins expressed in the cytoplasm of Plasmodium parasites can become targets of specific CD8(+) T cells during liver-stage infection.


[Anticoagulation of pregnant women with a mechanical heart valve prosthesis].
Patients with a mechanical heart valve prosthesis (MHVP) are usually anticoagulated with oral anticoagulants (OAC) to prevent thromboembolic complications. Considering the paucity of published data, the management of women with MHVP of childbearing age, who wish to become pregnant, still remains difficult and complicated. OAC may cause embryopathy during the first trimester, while neurologic complications, stillbirth and fetal death may appear during the second and third trimester. While the application of unfractionated heparin (UFH) in pregnant patients with MHVP may fail to prevent thromboembolic complications even with therapeutic dosage, only little is known about the application of body weight adjusted therapeutic dosages of low molecular weight heparin (LMWH). We report on 8 female patients, 7 with MHVP, one with atrial fibrillation, who were treated with LMWH during the whole pregnancy. No malformations or major bleeding complications were observed, no valve thrombosis or thromboembolic complications occurred. Three patients developed moderate heart failure during the third trimester, which resolved after treatment. In three patients, cesarean section was necessary, while the other five patients delivered spontaneously.Therefore, anticoagulation with body weight adjusted LMWH seems to be an alternative, safe and efficient treatment for pregnant women with MHVP. Prospective, randomized studies are needed to further evaluate this new therapeutic approach. The underlying heart disease represents a serious comorbid condition that requires continuous interdisciplinary monitoring.


Synergy of interleukin-4 and interferon-γ in arginase-1 production in RAW264.7 macrophages.
Interferon (IFN)-γ and interleukin (IL)-4 are considered to be important factors to regulate immune responses. Although the effects of IFN-γ or IL-4 on macrophage functions are well established, their cooperative action is not fully understood. Inducible nitric oxide synthase (iNOS) or arginase (Arg)-1 is a representative marker of M1 or M2 macrophages and plays a role in the acceleration or suppression of inflammatory responses. In the present study, we examined the effect of simultaneous treatment with IFN-γ and IL-4 on macrophage expression of iNOS and Arg-1 using the murine macrophage cell line RAW264.7. Protein production and mRNA expression of iNOS and Arg-1 were measured using immunoblotting and reverse transcription-polymerase chain reaction. Cell surface expression of CD86 and programmed death ligand (PD-L) 2 was analyzed using flow cytometry. IFN-γ or IL-4 increased iNOS or Arg-1 protein production, respectively. Of note, IL-4 combined with IFN-γ synergistically increased Arg-1 protein production, whereas IL-4 inhibited IFN-γ-induced iNOS production. This phenomenon was consistent with the mRNA levels. In addition, IL-4 combined with IFN-γ synergistically increased cell surface expression of PD-L2, which is involved in T cell suppression, whereas IL-4 completely inhibited IFN-γ-induced expression of CD86, which is responsible for T cell activation. In the present study, we found the synergy of IFN-γ and IL-4 in Arg-1 and PD-L2 expression. Thus, macrophages highly expressing Arg-1 and PD-L2 may be induced by both IFN-γ and IL-4 at the inflammatory site, and might play a role in the regulation of inflammatory immune responses.


Rates and equilibria for a photoisomerizable antagonist at the acetylcholine receptor of Electrophorus electroplaques.
Voltage-jump and light-flash experiments have been performed on isolated Electrophorus electroplaques exposed simultaneously to nicotinic agonists and to the photoisomerizable compound 2,2'-bis-[alpha-(trimethylammonium)methyl]-azobenzene (2BQ). Dose-response curves are shifted to the right in a nearly parallel fashion by 2BQ, which suggests competitive antagonism; dose-ratio analyses show apparent dissociation constants of 0.3 and 1 microM for the cis and trans isomers, respectively. Flash-induced trans----cis concentration jumps produce the expected decrease in agonist-induced conductance; the time constant is several tens of milliseconds. From the concentration dependence of these rates, we conclude that the association and dissociation rate constants for the cis-2BQ-receptor binding are approximately 10(8) M-1 s-1 and 60 s-1 at 20 degrees C; the Q10 is 3. Flash-induced cis----trans photoisomerizations produce molecular rearrangements of the ligand-receptor complex, but the resulting relaxations probably reflect the kinetics of buffered diffusion rather than of the interaction between trans-2BQ and the receptor. Antagonists seem to bind about an order of magnitude more slowly than agonists at nicotinic receptors.


The influence of evolutionary history on human health and disease.
Nearly all genetic variants that influence disease risk have human-specific origins; however, the systems they influence have ancient roots that often trace back to evolutionary events long before the origin of humans. Here, we review how advances in our understanding of the genetic architectures of diseases, recent human evolution and deep evolutionary history can help explain how and why humans in modern environments become ill. Human populations exhibit differences in the prevalence of many common and rare genetic diseases. These differences are largely the result of the diverse environmental, cultural, demographic and genetic histories of modern human populations. Synthesizing our growing knowledge of evolutionary history with genetic medicine, while accounting for environmental and social factors, will help to achieve the promise of personalized genomics and realize the potential hidden in an individual's DNA sequence to guide clinical decisions. In short, precision medicine is fundamentally evolutionary medicine, and integration of evolutionary perspectives into the clinic will support the realization of its full potential.


Random semiconductor lasers: scattered versus Fabry-Perot feedback.
As a result of growth imperfections, (Zn,Cd)O/ZnO quantum well structures exhibit random laser action. Fabrication of microresonators allows us to study and to compare directly cavity and scattered feedback. Our experimental and theoretical analysis shows that (i) pure random lasing generally requires a larger gain than in the standard Fabry-Perot regime, (ii) the presence of Mie scatterers in the semiconductor-based cavity does not substantially increase the lasing threshold, and (iii) the random feedback creates a subtle modal gain distribution that might be of particular importance for the dynamical properties, both with and without Fabry-Perot cavity.


[Central nervous system mycotic infections].
There has been an increased number of cases of fungal diseases of the central nervous system (CNS) during the past few years. This paper reviews current literature about these conditions, with emphasis on recent advances on diagnosis and therapy. While some fungi may cause disease in normal hosts, most of these microorganisms are opportunistics and affect immunocompromised hosts. With the exception of Candida albicans, that is a normal inhabitant of the intestinal tract, most fungi enter the body by inhalation or through skin abrasions. Common fungal diseases include aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, paracoccidioidomycosis, and phaeohyphomycosis. In general terms, fungal invasion of the CNS may produce one or more of the following clinical syndromes: subacute or chronic meningitis, encephalitis, parenchymal brain abscesses or granulomas, stroke, or myelopathy. Diagnosis may be difficult on clinical grounds, and data provided by neuroimaging studies or CSF examination is non-specific. Definitive diagnosis usually rest on the demonstration of the causal agent on body fluids or tissue samples. Early administration of amphotericin B, associated or not with the new azoles, is indicated to arrest the often fatal course of these conditions. Formerly considered rare diseases, the acquired immunodeficiency syndrome (AIDS) epidemic and the widespread use of corticosteroids and cytotoxic agents, have caused an increase in the prevalence of CNS mycosis. Development of potent antimycotic drugs have improved the prognosis of fungal diseases of the CNS. However, due to diagnostic delays or the presence of debilitating conditions, some patients still have torpid clinical courses despite proper therapy.


Length of incubation for enumerating nitrifying bacteria present in various environments.
The effect of incubation time on most-probable-number estimates of autotrophic nitrifying bacteria was investigated by using waters, rooted aquatic plants, sediments, and slimes as inoculum sources. Maximum most probable numbers of the NH4+-oxidizing group were attained in 20 to 55 days (median, 25). Estimates of NO2-oxidizers were highest at termination (103 to 113) days.


Diacetyl and acetoin production by Lactobacillus casei.
Agitation of broth cultures of Lactobacillus casei retarded cellular dry weight accumulation but enhanced production of both diacetyl and acetoin. Addition of pyruvate overcame this retardation, but addition of sulfhydryl-protecting reagents did not. Both pyruvate and citrate enhanced accumulated dry weight of L. casei incubated without agitation, but only pyruvate increased diacetyl accumulation. Both actively dividing cells and cells suspended in buffer converted pyruvate to diacetyl and acetoin. Maximum production of diacetyl and acetoin occurred during the late logarithmic or early stationary phases. Cells isolated from pyruvate- or citrate-containing cultures showed the greatest ability to convert pyruvate to diacetyl and acetoin. The optimum pH for diacetyl and acetoin formation by whole cells was in the range of 4.5 to 5.5. The presence of citrate or acetate enhanced diacetyl and acetoin formation by L. casei cells in buffer suspension.


Perceptions as the crucial link? The mediating role of neighborhood perceptions in the relationship between the neighborhood context and neighborhood cohesion.
This study examines the effects of neighborhood racial in-group size, economic deprivation and the prevalence of crime on neighborhood cohesion among U.S. whites. We explore to what extent residents' perceptions of their neighborhood mediate these macro-micro relationships. We use a recent individual-level data set, the American Social Fabric Study (2012/2013), enriched with contextual-level data from the U.S. Census Bureau (2010) and employ multi-level structural equation models. We show that the racial in-group size is positively related to neighborhood cohesion and that neighborhood cohesion is lower in communities with a high crime rate. Individuals' perceptions of the racial in-group size partly mediate the relationship between the objective racial in-group size and neighborhood cohesion. Residents' perceptions of unsafety from crime also appear to be a mediating factor, not only for the objective crime rate but also for the objective racial in-group size. This is in line with our idea that racial stereotypes link racial minorities to crime whereby neighborhoods with a large non-white population are perceived to be more unsafe. Residents of the same neighborhood differ in how they perceive the degree of economic decay of the neighborhood and this causes them to evaluate neighborhood cohesion differently, however perceptions of neighborhood economic decay do not explain the link between the objective neighborhood context and neighborhood cohesion.


Effect of omega-3 supplementation on the nutritional status of patients with pancreatic cancer: A protocol for systematic review of clinical trials.
Globally, pancreatic cancer is the seventh most common cause of cancer-related death in both sexes, accounting for 466,003 deaths and 495,773 new cases in 2020. The purpose of this study was to synthesize and evaluate evidence on the effects of omega-3 supplementation on the nutritional status of patients with pancreatic cancer. This systematic review protocol will be guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Five databases will be searched: MEDLINE/PubMed, CENTRAL Cochrane, EMBASE, Web of Science, and SCOPUS, with no restrictions on the publication date nor language. The internal validity and risk of bias of randomized controlled trials will be assessed using the revised Cochrane Risk-Of-Bias tool for randomized trials (RoB 2), whereas the risk of bias in non-randomized studies of interventions will be evaluated using the ROBINS-I. The heterogeneity among the studies will be assessed using the I2 statistic. Based on the results of this test, we will verify whether the meta-analysis would be feasible. If feasibility would be confirmed, a random-effect model analysis will be performed. For data analysis, the calculation of the pooled effect estimates will have a 95% confidence interval, while the alpha will be set to 0.05 using the R statistical software version 4.0.4. All methodological steps of this review will be performed independently by two reviewers and will be conducted and managed in the EPPI-Reviewer Software™. This review may be of particular interest to researchers and clinicians, given the low survival and overall burden of patients with pancreatic cancer. Furthermore, the results of this systematic review may contribute to the development of new nutritional interventions in these patients. To the best of our knowledge, this will be the first study to critically assess the scientific evidence and estimate the effect of omega-3 supplementation on the nutritional status of patients with pancreatic cancer. The review will perform a rigorous approach, adhering to the PRISMA Statement 2020 using a comprehensive and systematic search strategy in five databases and additional sources with no time period nor language restrictions.


Developing and Validating an Experience Sampling Measure of Aggression: The Aggression-ES Scale.
Experience sampling methodologies are likely to play an important role in advancing our understanding of momentary influences on aggression, including short-term antecedent psychological states and situations. In this study, we evaluate whether a newly developed experiencing sampling measure of aggression, the Aggression Experience Sampler (Aggression-ES), provides a valid and reliable measure of aggression in experience sampling contexts. Participants were a convenience sample of 23 young adults recruited from the local University community. Data were collected using an experience sampling smartphone application over 8 days. They were analyzed using multilevel structural equation modeling. Our results support the within- and between-person reliability and the criterion validity of the Aggression-ES. The Aggression-ES represents a good choice of measure for use in experience sampling studies of aggression. Further work in other samples will help to provide further validity evidence for the measure.


Oxidative stress in response to xenobiotics in the blue mussel Mytilus edulis L.: evidence for variation along a natural salinity gradient of the Baltic Sea.
Blue mussels (Mytilus edulis L.) collected at three sampling sites in each of three geographical regions (South, Middle, North) along the permanent longitudinal South-North salinity gradient of the Baltic Sea, were exposed for 10 days to copper (35ppb) or 95 octane petrol (0.3 per thousand). During the experiment, they were maintained at the respective sampling site salinity. Scope for growth (SFG) was determined, and biochemical stress markers (protein carbonyl groups, disulfide bond formation, and glutathione transferase (GST), and catalase (CAT) activities) were investigated in gill tissue upon termination of the experiment. Treatment and regional effects for SFG and protein carbonyl groups were all significant for petrol. The largest increase in protein carbonyl groups was observed in the North. Mussels from the southern, more saline ( approximately 7 per thousand) region had the highest SFG, and displayed the largest SFG decrease in response to treatment, indicating that they had the most energy available for allocation to stress response. They also displayed the least increase in the level of protein carbonyl groups. Mussels from the Northern, less saline ( approximately 5%) region had the highest degree of protein carbonyl groups in response to both treatments, and lowest average SFG. Silver stained diagonal gels for samples from one sampling site in South and North, respectively, demonstrated differences in disulfide bond profiles for both stress treatments. There was also a regional difference in the number of protein disulfides observed on diagonal gels. The most diverse protein disulfide response was found in South. No treatment related effects on GST and CAT activities were observed. We suggest that both SFG and protein carbonyl groups show that geographical difference in stress susceptibility, previously established between the North and the Baltic Seas, also apply on a regional scale within the Baltic Sea, along the salinity gradient.


Genetic and environmental variation in the visual properties of bluefin killifish, Lucania goodei.
Animals use their sensory systems to detect information about the external environment in order to find mates, locate food and habitat and avoid predators. Yet, there is little understanding of the relative amounts of genetic and/or environmental variation in sensory system properties. In this paper, we demonstrate genetic and environmental variation in opsin expression in a population of bluefin killifish. We measured expression of five opsins (which correlates with relative frequency of corresponding cones) using quantitative, real-time polymerase chain reaction for offspring from a breeding study where offspring were raised under different lighting conditions. Sire (i.e. genetic) effects were present for opsin found in yellow photopigment. Dam effects were present for opsins that create violet, blue and red photopigment. Lighting conditions affected expression of all opsins except SWS2A and mimicked the pattern found among populations. These results highlight the fact that sensory systems are both plastic and yet readily evolvable traits.


Effects on the Caco-2 Cells of a Hypoglycemic Protein from Lupin Seeds in a Solution and Adsorbed on Polystyrene Nanoparticles to Mimic a Complex Food Matrix.
The search for bioactivities influencing the human wellbeing of food proteins and peptides is a topic of broad and current interest. γ-Conglutin (γC) is a lupin seed protein drawing remarkable pharmacological and/or nutraceutical interest, as it is able to reduce hyperglycemia in humans and animal models. The present work deepens our investigations to understand the molecular basis of the in vitro effects of γC by testing the possible metabolic effects on cultivated Caco-2 cells. γC and its derived peptides (obtained via simulated gastrointestinal digestion) did not influence the cell viability at incubation times up to 24 h. The incubation of cells with native or digested γC caused no detectable inflammation processes mediated by Nuclear Factor kappa B (NFκB). We checked if treatment with γC or its derived peptides can elicit the expression of two peptide transporters (Pept-1 and Htp-1) by using an RT-qPCR approach. Native γC caused the halving of Pept-1 expression compared to untreated cells, but this effect disappeared when γC was digested. Either native γC or γC peptides reduced the expression levels of Hpt-1. Finally, this work also sheds light on the possible structural modifications of γC that may occur in the gastrointestinal tract, using an in vitro simulated dispersed system with polystyrene nanoparticles (NPs).


Toward understanding allosteric activation of thrombin: a conjecture for important roles of unbound Na(+) molecules around thrombin.
We shed light on important roles of unbound Na(+) molecules in enzymatic activation of thrombin. Molecular mechanism of Na(+)-activation of thrombin has been discussed in the context of allostery. However, the recent challenge to redesign K(+)-activated thrombin revealed that the allosteric interaction is insufficient to explain the mechanism. Under these circumstances, we have examined the roles of unbound Na(+) molecule in maximization of thrombin-substrate association reaction rate. We performed all-atomic molecular dynamics (MD) simulations of thrombin in the presence of three different cations; Li(+), Na(+), and Cs(+). Although these cations are commonly observed in the vicinity of the S1-pocket of thrombin, smaller cations are distributed more densely and extensively than larger ones. This suggests the two observation rules: (i) thrombin surrounded by Na(+) is at an advantage in the initial step of association reaction, namely, the formation of an encounter complex ensemble, and (ii) the presence of Na(+) molecules does not necessarily have an advantage in the final step of association reaction, namely, the formation of the stereospecific complex. In conclusion, we propose a conjecture that unbound Na(+) molecules also affect the maximization of rate constant of thrombin-substrate association reaction through optimally forming an encounter complex ensemble.


Redescription and Molecular Assessment of Relationships Among Three Species of Echeneibothrium (Rhinebothriidea: Echeneibothriidae) Parasitizing the Yellownose Skate, Dipturus chilensis, in Chile.
Much progress has recently been made in revising the taxonomic assignments of genera originally classified in the polyphyletic "Tetraphyllidea." Many of these genera, including Echeneibothrium, were accommodated in the order Rhinebothriidea. However, beyond this larger taxonomic action, little work has been conducted on this genus over the past 50 yr. Consequently, the criteria used for characterizing species of Echeneibothrium have lagged behind those typically used in more modern descriptions of elasmobranch-hosted cestode taxa. A series of collecting trips to Chile to obtain cestodes from the yellownose skate, Dipturus chilensis , provided a unique opportunity to apply modern morphological and molecular methods to investigate the 3 species of Echeneibothrium reported parasitizing this skate, specifically Echeneibothrium megalosoma, Echeneibothrium multiloculatum, and Echeneibothrium williamsi. In addition to redescribing all 3 species, using morphological data from light and scanning electron microscopy, maximum likelihood and bayesian inference phylogenetic analyses of the D1-D3 regions of the 28S rDNA gene were conducted to assess their relationships among other echeneibothriids for which comparable data are available. Sequencing of 59 specimens representing these 3 species of Echeneibothrium allowed us to assess the intra- and interspecific variation in the 28S rDNA gene. The redescriptions use standardized terminology for scolex morphology, proglottid anatomy, and microthrix forms and pattern; they also expand on the original descriptions to include data on scolex size, ovary size, vas deferens and vaginal configurations, testes arrangement, and genital pore position. Our morphological work led to a major reinterpretation of the scolex morphology with the recognition that all 3 species bear an apical bothridial sucker, rather than an apical loculus, prompting emendation of the diagnosis for the family Echeneibothriidae. The presence of a band of spinitriches at the apex of the apical modification of the scolex proper seems to represent an important feature for distinguishing the 2 portions of the myzorhynchus across species. Intraspecific variation ranged from 0 to 7 bp across species and interspecific variation ranged from a low of 39-46 bp between E. williamsi and E. multiloculatum to a high of 61-66 bp between E. multiloculatum and E. megalosoma. Phylogenetic analyses indicate that the 3 species of Echeneibothrium hosted by the yellownose skate are not each other's closest relatives, suggesting multiple colonization events of D. chilensis have occurred. Further phylogenetic investigation is also likely to confirm the status of the genus Pseudanthobothrium as a synonym of Echeneibothrium because its species generally group among members of Echeneibothrium.


An ethnographic study on the impact of a novel telemedicine-based support system in the operating room.
The Anesthesiology Control Tower (ACT) for operating rooms (ORs) remotely assesses the progress of surgeries and provides real-time perioperative risk alerts, communicating risk mitigation recommendations to bedside clinicians. We aim to identify and map ACT-OR nonroutine events (NREs)-risk-inducing or risk-mitigating workflow deviations-and ascertain ACT's impact on clinical workflow and patient safety. We used ethnographic methods including shadowing ACT and OR clinicians during 83 surgeries, artifact collection, chart reviews for decision alerts sent to the OR, and 10 clinician interviews. We used hybrid thematic analysis informed by a human-factors systems-oriented approach to assess ACT's role and impact on safety, conducting content analysis to assess NREs. Across 83 cases, 469 risk alerts were triggered, and the ACT sent 280 care recommendations to the OR. 135 NREs were observed. Critical factors facilitating ACT's role in supporting patient safety included providing backup support and offering a fresh-eye perspective on OR decisions. Factors impeding ACT included message timing and ACT and OR clinician cognitive lapses. Suggestions for improvement included tailoring ACT message content (structure, timing, presentation) and incorporating predictive analytics for advanced planning. ACT served as a safety net with remote surveillance features and as a learning healthcare system with feedback/auditing features. Supporting strategies include adaptive coordination and harnessing clinician/patient support to improve ACT's sustainability. Study insights inform future intraoperative telemedicine design considerations to mitigate safety risks. Incorporating similar remote technology enhancement into routine perioperative care could markedly improve safety and quality for millions of surgical patients.


Noise-induced memory in extended excitable systems.
We describe a form of memory exhibited by extended excitable systems driven by stochastic fluctuations. Under such conditions, the system self-organizes into a state characterized by power-law correlations, thus retaining long-term memory of previous states. The exponents are robust and model independent. We discuss implications of these results for the functioning of cortical neurons as well as for networks of neurons.


Differences in autophagy-associated mRNAs in peritoneal fluid of patients with endometriosis and gynecologic cancers.
Endometriosis and gynecologic cancer show similar patterns of invasion. Little is known about the roles of autophagy in endometriosis and, to date, the expression of autophagy-associated mRNAs has not been compared in patients with endometriosis and gynecologic cancers. This study therefore compared the levels of expression of autophagy-associated mRNAs in patients with endometriosis and gynecologic cancers. The levels of autophagy mRNAs, including those encoding mTOR, P13KC3, Beclin-1, Bcl-2, LC3 II, FLIP, Rubicon, BIRC2 and BIRC5, were measured by real time polymerase chain reaction in peritoneal fluid of 27 patients with benign masses (control group), 42 patients with endometriosis, and 43 patients with gynecologic (ovarian, uterine, and cervical) cancers. Findings in the three groups were compared. Autophagy mRNAs were present in all samples from patients with endometriosis and gynecologic cancers. The levels of PI3K, FLIP, and Rubicon mRNAs were significantly higher in the endometriosis than in the control group (p < 0.05 each). Compared with the gynecologic cancer group, the levels of LC3II and FLIP mRNAs were significantly lower, and the levels of Beclin-1 and Rubicon mRNAs significantly higher, in the endometriosis group (p < 0.05 each). Levels of PI3K and FLIP mRNA were significantly higher in the endometriosis and gynecologic cancer groups than in the control group (p < 0.05 each). PI3K, FLIP, and Rubicon mRNAs are closely associated with the pathogenesis of endometriosis. The similar increases in PI3K and FLIP mRNA expression observed in patients with endometriosis and gynecologic cancer suggest that these conditions have similar autophagic characteristics. The lower levels of Beclin-1 mRNA in the gynecologic cancer than in other two groups suggest that lower Beclin-1 mRNA levels increase the likelihood of developing gynecologic cancer.


Measuring exposure of e-waste dismantlers in Dhaka Bangladesh to organophosphate esters and halogenated flame retardants using silicone wristbands and T-shirts.
Silicone (polydimethylsiloxane or PDMS) wristbands and cotton T-shirts were used to assess the exposure of e-waste recyclers in Dhaka, Bangladesh to polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), dechlorane plus (DPs), and organophosphate esters (OPEs). The median surface-normalized uptake rates of PBDEs, NBFRs, DPs, and OPEs were 170, 8.5, 4.8, and 270 ng/dm2/h for wristbands and 5.4, 2.0, 0.94, and 23 ng/dm2/h for T-shirts, respectively. Concentrations of Tris(2-chloroethyl) phosphate (TCEP), Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), Tri-m-cresyl phosphate (TmCP), Bis(2-ethlyhexyl) tetrabromophthalate (BEH-TEBP), and Dechlorane plus (DPs) in wristbands were significantly correlated with those in T-shirts. Wristbands accumulated ~7 times more mass than T-shirts, especially of compounds expected to be mainly in the gas phase. We introduce the silicone "sandwich" method to approximate the easily releasable fraction (ERF) from T-shirts, hypothesized to be related to dermal exposure. ERFs varied from 6 to 75% of total chemical accumulated by T-shirts and were significantly negatively correlated with compounds' octanol-air partition coefficient (log Koa). The median daily exposure doses via dermal transfer from the front of the T-shirt to the front body trunk were 0.32, 0.13, 0.11, and 9.1 ng/kg-BW/day for PBDEs, NBFRs, DPs, and OPEs, respectively. The evidence of e-waste recycler exposure to flame retardants in this low income country, lacking protective personal equipment, calls for measures to minimize their exposure and for chemical management regulations to consider exposures to chemicals in waste products.


Nitrogen deposition and prey nitrogen uptake control the nutrition of the carnivorous plant Drosera rotundifolia.
Nitrogen (N) deposition has important negative impacts on natural and semi-natural ecosystems, impacting on biotic interactions across trophic levels. Low-nutrient systems are particularly sensitive to changes in N inputs and are therefore more vulnerable to N deposition. Carnivorous plants are often part of these ecosystems partly because of the additional nutrients obtained from prey. We studied the impact of N deposition on the nutrition of the carnivorous plant Drosera rotundifolia growing on 16 ombrotrophic bogs across Europe. We measured tissue N, phosphorus (P) and potassium (K) concentrations and prey and root N uptake using a natural abundance stable isotope approach. Our aim was to test the impact of N deposition on D. rotundifolia prey and root N uptake, and nutrient stoichiometry. D. rotundifolia root N uptake was strongly affected by N deposition, possibly resulting in reduced N limitation. The contribution of prey N to the N contained in D. rotundifolia ranged from 20 to 60%. N deposition reduced the maximum amount of N derived from prey, but this varied below this maximum. D. rotundifolia tissue N concentrations were a product of both root N availability and prey N uptake. Increased prey N uptake was correlated with increased tissue P concentrations indicating uptake of P from prey. N deposition therefore reduced the strength of a carnivorous plant-prey interaction, resulting in a reduction in nutrient transfer between trophic levels. We suggest that N deposition has a negative impact on D. rotundifolia and that responses to N deposition might be strongly site specific.


Acute renal failure in Nepal Medical College Teaching Hospital.
Total 45 patients (male 27 and female 18) of acute renal failure (ARF) admitted in Nepal Medical College Teaching Hospital over a period of 12 months (1st of Baisakh 2064 BS to 31st of Chaitra 2064 BS) were enrolled in the study. Sixty four percent of study population were of age group 21-60 years. Acute Gastroenteritis 33, sepsis 5, hemorrhage 2, others 5 were the different causes of ARF. Serum creatinine of the study population before and after treatment was 4.35 +/- 2.72 and 1.38 +/- 0.72 mg/dl respectively. Similarly serum urea before and after treatment was 101.78 +/- 57.56 and 42.60 +/- 30.46 mg/dl respectively. Thirty three patients were managed by non dialytic modality of therapy and 12 patients needed hemodialysis. Blood urea of those patients who underwent nondialytic therapy was significantly less than of those who underwent hemodialysis (80.65 +/- 38.21 vs. 151.08 +/- 66.22; p = 0.004). Serum creatinine was also significantly lower in nondialytic therapy group (3.15 +/- 1.15 vs. 7.64 +/- 3.10; p = 0.000) ARF patients with very high urea, creatinine and disturbed electrolytes required dialysis. Average session of hemodialysis was 3.4. Thirty five patients were cured, 6 left against medical advice, 3 were discharged on request, and one patient of sepsis expired during the course of treatment. Acute gastroenteritis was the leading cause of ARF and outcome was excellent even without dialysis in most of the cases provided the treatment was started early and appropriately.


Enhancing nursing documentation in Kazakhstan: assessing utilization and standardization for improving patient care.
This article stresses the importance of comprehensive nursing documentation in scientific medicine and discusses the adoption of standardized terminologies in Europe. The study also presents findings from a cross-sectional study conducted in Kazakhstan, assessing the utilization of standard operating procedures and nursing documentation in various clinical scenarios. The aim was evaluate the level of use of the form of nursing documentation and Standard Operating Procedure within the framework of reforming the Republic of Kazakhstan. During the period from December 2021 to February 2022, a cross-sectional study was conducted in Kazakhstan, involving a randomly selected sample of nurses with technical and vocational education as well as those with applied/academic baccalaureate degrees in nursing. In this cross-sectional study of 2,263 female nurses, 75.3% were nurse practitioners, and 44% held the highest qualification category. Awareness levels varied, with around 64.7% aware of the pilot program for care services, 65.8% aware of the deputy head position, and 73.8% familiar with the "extended practice nurse" role. Only 55.2% knew about the International Clinical Nursing Classification, and 54.5% observed changes in their nursing approach due to education. The limb edema measurement checklist was not used by the majority (88.4%) of respondents, and 68% did not utilize the antibiotic susceptibility testing checklist. Various other checklists and algorithms had limited utilization, with percentages ranging from 9.1 to 69.3%, indicating varying levels of adoption among participants. For assisting children with cerebral palsy, the "Assessment of hand use capacity according to the MACS classification system" was utilized by 9.1%, while 90.9% did not employ it. In the context of communication, 30.7% of the respondents utilized the "Algorithm of actions of a medical registrar when communicating with a patient," while 69.3% did not use it. These findings highlight variable adoption rates among participants for these medical procedures and protocols. In Kazakhstan, nursing documentation forms and Standard Operating Procedures face challenges and limited utilization, but their implementation has shown positive impacts on patient care and healthcare outcomes. Overcoming resistance to change, increasing awareness, and addressing resource constraints are essential for further improvement.


Soybean hull and its effect on atherosclerosis in non-human primates (Macaca fascicularis).
Twenty five monkeys were used in this experiment. They were divided into 5 groups with 5 animals as the replicates in each group and were adapted for two weeks to the environment before the data were collected. The animals were subjected to 5 experimental diets, i.e. T1 (Basal diet); T2 (Basal diet + palm oil); T3 (Basal diet + palm oil + soybean hull); T4 (Basal diet + cholesterol) and T5 (Basal diet + cholesterol + soybean hull). The diets were given for a period of 8 months and water were given ad lib. Blood serum was taken before and during the experiment. The cholesterol, triglycerides, LDL and HDL were measured using the spectrophotometric method. At the end of the experiment thorax surgery was performed on the animals under general anesthesia. The aorta was removed surgically for histopathological observation stained with hematoxylin and eosine. The results showed that the soybean hull decreased the serum cholesterol level in the groups given palm oil (T2 vs T3) and the groups given cholesterol (T4 vs T5) i.e.: 163.4 vs 124.7 mg/dl and 359 vs 288.5 mg/dl respectively. The soybean hull did not significantly affect the serum triglyceride nor the LDL level when palm oil was given in the diet, but it significantly decreased the two parameters where cholesterol was given in the diet (102.5 vs 98.6 mg/dl triglyceride) and (231.9 vs 183 mg/dl LDL). The soybean hull did not seem to affect the HDL level. Histopathological observation of the aorta indicated that given T1, T2, T3, T4 and T5 caused 45%, 41.67%, 31.25%, 86.25% and 53.38% lesion (Atheroma arteriale) respectively. It was concluded that the soybean hull given in the diet has the ability to prevent the development of atherosclerosis in the aorta of the experimental animals.


A machine vision system with CCD cameras for patient positioning in radiotherapy: a preliminary report.
To determine positioning accuracy of a machine vision system in radiotherapy. The machine vision system was composed of 640 x 480 pixel CCD cameras and computerized control systems. For image acquisition, the phantom was set up for the reference position and a single CCD camera was positioned 1.5 m from the isocenter. The image data of the fiducial marker with 1.5 mm lead pellet on the lateral surface of the phantom was captured onto the CCD, and then the position of the marker was accurately calculated. The phantom was moved 0.25, 0.50, 0.75, 1.00, 2.00, and 3.00 mm from the reference position, using a micrometer head. The position of the fiducial marker was analyzed using a kilo-voltage fluoroscopic imaging system and a machine vision system. Using fluoroscopic images, the discrepancy between the actual movement of the phantom by micrometer heads and the measurement was found to be 0.12 +/- 0.05 mm (mean +/- standard deviation). In contrast, the detection of the movement by the machine vision system coincided with the discrepancy of 0.0067 +/- 0.0048 mm. This study suggests that the machine vision system can be used to measure small changes in patient position with a resolution of less than 0.1 mm.


MicroRNAs of Epstein-Barr Virus Attenuate T-Cell-Mediated Immune Control In Vivo.
The human persistent and oncogenic Epstein-Barr virus (EBV) was one of the first viruses that were described to express viral microRNAs (miRNAs). These have been proposed to modulate many host and viral functions, but their predominant role in vivo has remained unclear. We compared recombinant EBVs expressing or lacking miRNAs during in vivo infection of mice with reconstituted human immune system components and found that miRNA-deficient EBV replicates to lower viral titers with decreased frequencies of proliferating EBV-infected B cells. In response, activated cytotoxic EBV-specific T cells expand to lower frequencies than during infection with miRNA-expressing EBV. However, when we depleted CD8+ T cells the miRNA-deficient virus reached similar viral loads as wild-type EBV, increasing by more than 200-fold in the spleens of infected animals. Furthermore, CD8+ T cell depletion resulted in lymphoma formation in the majority of animals after miRNA-deficient EBV infection, while no tumors emerged when CD8+ T cells were present. Thus, miRNAs mainly serve the purpose of immune evasion from T cells in vivo and could become a therapeutic target to render EBV-associated malignancies more immunogenic.IMPORTANCE Epstein-Barr virus (EBV) infects the majority of the human population and usually persists asymptomatically within its host. Nevertheless, EBV is the causative agent for infectious mononucleosis (IM) and for lymphoproliferative disorders, including Burkitt and Hodgkin lymphomas. The immune system of the infected host is thought to prevent tumor formation in healthy virus carriers. EBV was one of the first viruses described to express miRNAs, and many host and viral targets were identified for these in vitro However, their role during EBV infection in vivo remained unclear. This work is the first to describe that EBV miRNAs mainly increase viremia and virus-associated lymphomas through dampening antigen recognition by adaptive immune responses in mice with reconstituted immune responses. Currently, there is no prophylactic or therapeutic treatment to restrict IM or EBV-associated malignancies; thus, targeting EBV miRNAs could promote immune responses and limit EBV-associated pathologies.


Dentin wall adaptation of multiphase versus temperature thermoplasticized gutta-percha. A scanning electron microscopic study.
An in-vitro study was designed to compare dentin wall adaptation of Multiphase gutta-percha root canal obturation technique versus high temperature thermoplasticized gutta-percha (Obtura) in the presence and absence of smear layer. Forty single rooted teeth with straight canals were used. After decapitation roots were divided into two equal groups. Group (I) received final irrigation with EDTA and Sodium hypochlorite (NaOCI) to remove the smear layer, while roots in Group (II) were irrigated with NaOCI alone. Each group was then subdivided into two subgroups to represent the two filling techniques. Teeth were sectioned longitudinally and viewed under scanning electron microscope. Multiphase gutta-percha showed excellent adaptation to canal wall, specially in the absence of smear layer and displayed a homogeneous mass with little amount of voids than the Obtura system.


Effect of relative humidity on dynamic aerosols of adenovirus 12.
Dynamic aerosols of adenovirus 12 were generated in the same Henderson apparatus under conditions of high, medium, and low relative humidity. High relative humidities resulted in more recovery of adenovirus 12 from aerosols and lungs of newborn Syrian hamsters. At 89, 51, and 32% relative humidity, the total infectious virus recovered from a 20-min aerosol was 10(6.7), 10(6.0), and 10(4.3) TCD(50), respectively. Hamsters exposed to these 20-min aerosols retained measured lung doses of 10(3.0), 10(2.4), and 10(1.0) TCD(50), respectively. The measured retained lung doses were compared to calculated inhaled lung doses based on both total virus aerosolized and total virus recovery from the aerosols.


The DNA binding domain of estrogen receptor alpha is required for high-affinity nuclear interaction induced by estradiol.
Estrogen receptor alpha (ER) is a member of the nuclear hormone receptor family, which upon binding estrogen shows increased apparent affinity for nuclear components (tight nuclear binding). The nuclear components that mediate this tight nuclear binding have been proposed to include both ER-DNA interactions and ER-protein interactions. In this paper, we demonstrate that tight nuclear binding of ER upon estrogen occupation requires ER-DNA interactions. Hormone-bound ER can be extracted from the nucleus in low-salt buffer using various polyanions, which mimic the phosphate backbone of DNA. The importance of specific ER-DNA interactions in mediating tight nuclear binding is also supported by the 380-fold lower concentration of the ERE oligonucleotide necessary to extract estrogen-occupied ER from the nucleus compared to the polyanions. We also demonstrate that estrogen-induced tight nuclear binding requires both the nuclear localization domain and the DNA binding domain of ER. Finally, enzymatic degradation of nuclear DNA allows us to recover 45% of tight nuclear-bound ER. We further demonstrate that ER-AIB1 interaction is not required for estrogen-induced tight nuclear binding. Taken together, we propose a model in which tight nuclear binding of the estrogen-occupied ER is predominantly mediated by ER-DNA interactions. The effects of estrogen binding on altering DNA binding in whole cells are proposed to occur through estrogen-induced changes in ER-chaperone protein interactions, which alter the DNA accessibility of ER but do not directly change the affinity of the ER for DNA, which is similar for both unoccupied and occupied ER.


Effect of Noninfectious Wound Complications after Mastectomy on Subsequent Surgical Procedures and Early Implant Loss.
Noninfectious wound complications (NIWCs) after mastectomy are not routinely tracked and data are generally limited to single-center studies. Our objective was to determine the rates of NIWCs among women undergoing mastectomy and assess the impact of immediate reconstruction (IR). We established a retrospective cohort using commercial claims data of women aged 18 to 64 years with procedure codes for mastectomy from January 2004 through December 2011. Noninfectious wound complications within 180 days after operation were identified by ICD-9-CM diagnosis codes and rates were compared among mastectomy with and without autologous flap and/or implant IR. There were 18,696 procedures (10,836 [58%] with IR) among 18,085 women identified. The overall NIWC rate was 9.2% (1,714 of 18,696); 56% required surgical treatment. The NIWC rates were 5.8% (455 of 7,860) after mastectomy only, 10.3% (843 of 8,217) after mastectomy plus implant, 17.4% (337 of 1,942) after mastectomy plus flap, and 11.7% (79 of 677) after mastectomy plus flap and implant (p < 0.001). Rates of individual NIWCs varied by specific complication and procedure type, ranging from 0.5% for fat necrosis after mastectomy only, to 7.2% for dehiscence after mastectomy plus flap. The percentage of NIWCs resulting in surgical wound care varied from 50% (210 of 416) for mastectomy plus flap, to 60% (507 of 843) for mastectomy plus implant. Early implant removal within 60 days occurred after 6.2% of mastectomy plus implant; 66% of the early implant removals were due to NIWCs and/or surgical site infection. The rate of NIWC was approximately 2-fold higher after mastectomy with IR than after mastectomy only. Noninfectious wound complications were associated with additional surgical treatment, particularly in women with implant reconstruction, and with early implant loss.


Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
Study Type - Therapy (cohort) Level of Evidence 4. What's known on the subject? and What does the study add? Accumulating evidence suggests that inflammation may contribute to the development of BPH and LUTS. Therefore, it is plausible that anti-inflammatory agents, such as aspirin and other NSAIDs, may reduce the risk of BPH/LUTS, as was observed in a recent analysis of daily aspirin use and BPH/LUTS risk in the Olmsted County Study of Urinary Symptoms and Health Status in Men. The present study, conducted in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, found no association for recent aspirin or ibuprofen use with the risk of BPH/LUTS. To investigate the relationship between non-steroidal anti-inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)-related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development. At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate-specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n= 4771). • During follow-up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006-2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia. • Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self-reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥30 mL on any follow-up DRE) and elevation in PSA level (>1.4 ng/mL on any follow-up PSA test). Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92-1.21, P= 0.043-0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98-1.11, P-trends = 0.10-0.99) with incident BPH/LUTS. The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.


Enhancement of spectral purity of injection-seeded titanium:sapphire laser by cavity locking and stimulated Brillouin scattering.
We report improvements to and better characterization of the spectral purity of a diode laser injection-seeded, cavity-locked titanium sapphire laser that serves as the source for a previously reported rubidium vapor spectrally filtered Thomson scattering apparatus at 780.24 nm. In a detailed set of measurements the spectral purity P of the laser, defined as the ratio ofthe narrowband component of the laser output to the total output, has been studied as a function of frequency mismatch between the seed laser frequency and the central frequency of the unseeded cavity. It is found that spectral purity exceeding 0.999 can be obtained for a seed-cavity mismatch as high as +/- 0.25 nm, corresponding to approximately 950 cavity longitudinal-mode spacings and as high as approximately 0.9999 for a cavity-seed mismatch in the range +/- 0.10 nm (380 mode spacings). It is also shown that the addition of an external-cavity stimulated Brillouin-scattering phase-conjugate mirror increases both the spectral purity, to a minimum of 0.99999, and the cavity-seed mismatch range, to +/- 0.25 nm, for which this maximum effective purity is obtained.


The pattern of neurological disease at Kenyatta National Hospital.
A retrospective survey of neurological disease seen at KNH in medical wards and medical outpatients clinics is presented. Neurological diseases constituted 7.5% of all medical conditions seen over that period. Infections especially meningitis were found to be the commonest. The 3 commonest diseases were meningitis (23.1%), epilepsy (16.6%) and cerebrovascular diseases (15.0%). Neurosyphilis, trypanosomiasis, and leprosy only infrequently seen (1-2 cases annually). Multiple sclerosis seen regularly through infrequently since 1981. The trend of the 3 commonest conditions is presented and a downward trend is noted. The mortality patterns for the 3 commonest diseases is also presented.


[Tuberculosis: yesterday, today, tomorrow].
The historical aspects of phisiology are briefly outlined. The main factors that promote the prevalence of tuberculosis are characterized. The present-day tuberculosis epidemiological situation makes one to correct antituberculous measures and with the use of new investigations and developments to improve the identification of patients with tuberculosis, primarily those with contagious types of the disease, to introduce the currently available short-term regimens of 2-stage drug therapy, to design novel agents and depot formulations of the well known ones. Further investigations are required to search for a new tuberculosis vaccine.


Acute kidney injury in children hospitalized with a relapse of nephrotic syndrome: A short-term outcome study.
Children with nephrotic syndrome (NS) have a number of potential risk factors for the development of acute kidney injury (AKI) including intravascular volume depletion, infection, exposure to nephrotoxic medication, and renal interstitial edema. This study was aimed to determine the incidence of AKI in children hospitalized with a relapse of NS and its short-term outcome. This prospective observational study was conducted from February 2017 to January 2018 at a tertiary care teaching hospital. A total of 54 children and adolescents (1-18 years) hospitalized with a diagnosis of NS and relapse with/or without other complications were enrolled. Clinical data and examination were recorded. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria and Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (p-RIFLE) classification. Children who developed AKI during the first two weeks of hospitalization were followed up till recovery or six weeks whichever was earlier to determine the outcome and factors predisposing to AKI. The mean age of the study population was 59.5 months and 35 (64.8%) patients were male. Of the 54 patients hospitalized, 42 (77.8%) were admitted with infection-associated relapses while 22.2% of children had relapse alone. Diarrhea and spontaneous bacterial peritonitis were the most common infections (26.1% each) followed by urinary tract infections in 19% and pneumonia in 14.3%. Twenty-three (42.6%) children developed AKI according to the KDIGO definition and 27 (50%) using the pRIFLE classification. Fourteen (60.9%) had stage 2 AKI while 21.7% had stage 3 AKI. Infections [odds ratio (OR) 1.24] and use of angiotensin-converting enzyme inhibitors (ACEI) (OR 2.3) were the most common predisposing factors for AKI. The mean recovery time for AKI was 7.34 days. Development of AKI was associated with prolonged hospital stay (12.57 vs.8.55 days P <0.01) and delayed recovery. At the end of follow-up all children recovered from AKI. The incidence of AKI in children hospitalized with complications of NS is high. While the occurrence of these AKI episodes may appear transient, a recurrence of such episodes may be detrimental to the long-term outcome of children with NS. Infections and the use of ACEI during relapses are risk factor for the occurrence of AKI.


Expression of MicroRNA-146a and MicroRNA-155 in Placental Villi in Early- and Late-Onset Preeclampsia.
We studied the expression of microRNA-146a and microRNA-155 in placental villi from 18 women (26-39 weeks of gestation) of reproductive age with early- or late-onset preeclampsia. The reference group consisted of women with physiological pregnancy and full-term gestation and with preterm birth after caesarian section on gestation week 26-31. MicroRNA-146a and microRNA-155 were detected by in situ hybridization with digoxigenin on paraffin sections. It was found that the expression of microRNA-146a in both syncytiotrophoblast of the intermediate villi and syncytial knots was lower at late-onset preeclampsia than at physiologic pregnancy of full-term period (p=0.037 and p=0.001 respectively). The expression of microRNA-155 in syncytiotrophoblast of intermediate placental villi in early-onset preeclampsia was higher than in group with preterm delivery (p=0.003). However, in syncytiotrophoblast of intermediate villi and in syncytial knots, the expression of microRNA-155 was lower at late-onset preeclampsia in comparison with full-term physiological pregnancy (p=0.005). In addition, the expression of microRNA-146a and microRNA-155 did not increase in the later terms in preeclampsia, while in the reference groups demonstrating gradual increase in the expression of these markers with increasing gestational age. Expression microRNA-146a and microRNA-155 little differed in early- and late-onset preeclampsia. These findings suggest that different variants of preeclampsia are probably characterized by common pathogenetic pathways. Damaged trophoblast cannot maintain of microRNAs synthesis at the required level, which determines the formation of a vicious circle in preeclampsia and further progression of the disease.


Mastering the donor eye: a new device for obtaining donor corneal discs.
In recognition of the many inexactitudes involved in cutting donor corneal discs, a new instrument is here described which should help to eliminate many of then, and its mode of use is outlined. For a long time instruments available to assist the corneal surgeon in his management of donor material have been inadequate. Many devices are awkward to use, or give rise to donor discs of an unreliable or uneven edge profile. In an attempt to overcome these difficulties we have designed, produced and tested a new instrument which we feel represents an advance. Because different surgeons use fresh or stored material, and because some prefer to trephine from the epithelial surface while others opt to punch from the endothelium, we have endeavoured to meet all these requirements.


De novo biosynthetic profiling of high abundance proteins in cystic fibrosis lung epithelial cells.
In previous studies with cystic fibrosis (CF) IB3-1 lung epithelial cells in culture, we identified 194 unique high abundance proteins by conventional two-dimensional gel electrophoresis and mass spectrometry (Pollard, H. B., Ji, X.-D., Jozwik, C. J., and Jacobowitz, D. M. (2005) High abundance protein profiling of cystic fibrosis lung epithelial cells. Proteomics 5, 2210-2226). In the present work we compared the IB3-1 cells with IB3-1/S9 daughter cells repaired by gene transfer with AAV-(wild type)CFTR. We report that gene transfer resulted in significant changes in silver stain intensity of only 20 of the 194 proteins. However, simultaneous measurement of de novo biosynthetic rates with [(35)S]methionine of all 194 proteins in both cell types resulted in the identification of an additional 31 CF-specific proteins. Of the 51 proteins identified by this hybrid approach, only six proteins changed similarly in both the mass and kinetics categories. This kinetic portion of the high abundance CF proteome, hidden from direct analysis of abundance, included proteins from transcription and signaling pathways such as NFkappaB, chaperones such as HSC70, cytoskeletal proteins, and others. Connectivity analysis indicated that approximately 30% of the 51-member hybrid high abundance CF proteome interacts with the NFkappaB signaling pathway. In conclusion, measurement of biosynthetic rates on a global scale can be used to identify disease-specific differences within the high abundance cystic fibrosis proteome. Most of these kinetically defined proteins are unaffected in expression level when using conventional silver stain analysis. We anticipate that this novel hybrid approach to discovery of the high abundance CF proteome will find general application to other proteomic problems in biology and medicine.


Association between exposure to per- and perfluoroalkyl substances (PFAS) and reproductive hormones in human: A systematic review and meta-analysis.
Per- and polyfluoroalkyl substances (PFAS) is persistent endocrine disrupting chemicals. Previous evidence suggests that exposure to PFAS is associated with reproductive hormone levels, but the results of relevant studies are inconsistent. The objective of our study is to determine the association between exposure to PFAS and reproductive hormone levels in gender-specific general population. Based on scientific search strategies, we systematically searched PubMed, Web of Science, Embase, Medline, and Scopus to obtain the eligible studies published before January 21, 2023. The quality of the included articles was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias tool. We combined the β coefficient and 95% confidence intervals (CI) using Stata.17 with random-effect model or fixed-effect model. We also performed subgroup analysis, sensitivity analysis, and Begger's and Egger's tests. Eleven studies involving 7714 participants were included. Meta-analysis showed that PFHxS exposure was positively associated with estradiol (E2) levels in female [β = 0.030, 95% CI: (0.013, 0.046), P = 0.000]. A negative association was found between PFOA [β = -0.012, 95% CI: (-0.023, -0.002), P = 0.017] and PFOS [β = -0.011; 95% CI: (-0.021, -0.000), P = 0.042] exposure with male testosterone (TT) levels. In the subgroup analysis, there were stronger associations in children than in adults. And the high heterogeneity was mainly due to the cross-sectional studies. Publication bias was not found in most of the analyses. Our study showed that PFAS exposure was significantly associated with reproductive hormone levels. Further related studies are needed to identify the association and potential mechanism in the future.


Spatiotemporal tuning of the facilitation of biological motion perception by concurrent motor execution.
The execution of motor behavior influences concurrent visual action observation and especially the perception of biological motion. The neural mechanisms underlying this interaction between perception and motor execution are not exactly known. In addition, the available experimental evidence is partially inconsistent because previous studies have reported facilitation as well as impairments of action perception by concurrent execution. Exploiting a novel virtual reality paradigm, we investigated the spatiotemporal tuning of the influence of motor execution on the perception of biological motion within a signal-detection task. Human observers were presented with point-light stimuli that were controlled by their own movements. Participants had to detect a point-light arm in a scrambled mask, either while executing waving movements or without concurrent motor execution (baseline). The temporal and spatial coherence between the observed and executed movements was parametrically varied. We found a systematic tuning of the facilitatory versus inhibitory influences of motor execution on biological motion detection with respect to the temporal and the spatial congruency between observed and executed movements. Specifically, we found a gradual transition between facilitatory and inhibitory interactions for decreasing temporal synchrony and spatial congruency. This result provides evidence for a spatiotemporally highly selective coupling between dynamic motor representations and neural structures involved in the visual processing of biological motion. In addition, our study offers a unifying explanation that reconciles contradicting results about modulatory effects of motor execution on biological motion perception in previous studies.


An aptamer-tethered DNA origami amplifier for sensitive and accurate imaging of intracellular microRNA.
Accurate detection and imaging of low-abundance microRNA (miRNA) in living cells are essential for the diagnosis and prognosis of diseases. Designing nanoprobes with resistance to enzyme degradation, effective cell-binding, and efficient signal amplification is crucial for in vivo imaging. In this study, we present an aptamer-tethered DNA origami amplifier (ADOA) that functions inside living cells to detect miRNA with high sensitivity and stability. In the design, cancer cell-targeting aptamers were tethered onto the border of the DNA origami to improve the discrimination between cancer cells and normal cells. Two substrate modules for the intramolecular entropy-driven reaction (EDR) circuit were alternately arranged on the DNA origami plane. The target miRNA will initiate the sequential hybridization of the two substrate modules on the DNA origami, generating amplified fluorescence signals. The proposed ADOA achieved an accelerated cascade reaction due to the "confinement effect" and significantly enhanced the sensitivity compared with a traditional EDR. Meanwhile, with the rigid structure of the DNA origami, the ADOA possessed excellent signalling stability in living cells. Therefore, the ADOA could expand the application of DNA origami in miRNA sensing and has potential value in early-stage clinical diagnosis.


Clinical management of Staphylococcus aureus bacteremia: a review.
Several management strategies may improve outcomes in patients with Staphylococcus aureus bacteremia. To review evidence of management strategies for S. aureus bacteremia to determine whether transesophageal echocardiography is necessary in all adult cases and what is the optimal antibiotic therapy for methicillin-resistant S. aureus (MRSA) bacteremia. A PubMed search from inception through May 2014 was performed to identify studies addressing the role of transesophageal echocardiography in S. aureus bacteremia. A second search of PubMed, EMBASE, and the Cochrane Library from January 1990 through May 2014 was performed to find studies addressing antibiotic treatment for MRSA bacteremia. Studies reporting outcomes from antibiotic therapy for MRSA bacteremia were included. All searches, which were limited to English and focused on adults, were augmented by review of bibliographic references from included studies. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation system with consensus of independent evaluations by at least 2 of the authors. In 9 studies with a total of 4050 patients, use of transesophageal echocardiography was associated with higher rates of a diagnosis of endocarditis (14%-28%) compared with transthoracic echocardiography (2%-15%). In 4 studies, clinical or transthoracic echocardiography findings did not predict subsequent transesophageal echocardiography findings of endocarditis. Five studies identified clinical or transthoracic echocardiography characteristics associated with low risk of endocarditis (negative predictive values from 93% to 100%). Characteristics associated with a low risk of endocarditis include absence of a permanent intracardiac device, sterile follow-up blood cultures within 4 days after the initial set, no hemodialysis dependence, nosocomial acquisition of S. aureus bacteremia, absence of secondary foci of infection, and no clinical signs of infective endocarditis. Of 81 studies of antibiotic therapy for MRSA bacteremia, only 1 high-quality trial was identified. In that study of 246 patients with S. aureus bacteremia, daptomycin was not inferior to vancomycin or an antistaphylococcal penicillin, each in combination with low-dose, short-course gentamicin (clinical success rate, 44.2% [53/120] vs 41.7% [48/115]; absolute difference, 2.4% [95% CI, -10.2% to 15.1%]). All adult patients with S. aureus bacteremia should undergo echocardiography. Characteristics of low-risk patients with S. aureus bacteremia for whom transesophageal echocardiography can be safely avoided have been identified. Vancomycin and daptomycin are the first-line antibiotic choices for MRSA bacteremia. Well-designed studies to address the management of S. aureus bacteremia are needed.


Lessons Learned by Community Stakeholders in the Massachusetts Childhood Obesity Research Demonstration (MA-CORD) Project, 2013-2014.
Childhood obesity is a multifaceted disease that requires sustainable, multidimensional approaches that support change at the individual, community, and systems levels. The Massachusetts Childhood Obesity Research Demonstration project addressed this need by using clinical and public health evidence-based methods to prevent childhood obesity. To date, little information is known about successes and lessons learned from implementing such large-scale interventions. To address this gap, we examined perspectives of community stakeholders from various sectors on successes achieved and lessons learned during the implementation process. We conducted 39 semistructured interviews with key stakeholders from 6 community sectors in 2 low-income communities from November 2013 through April 2014, during project implementation. Interviews were audio-recorded, transcribed, and analyzed by using the constant comparative method. Data were analyzed by using QSR NVivo 10. Successes included increased parental involvement in children's health and education, increased connections within participating organizations and within the broader community, changes in organizational policies and environments to better support healthy living, and improvements in health behaviors in children, parents, and stakeholders. Lessons learned included the importance of obtaining administrative and leadership support, involving key stakeholders early in the program planning process, creating buffers that allow for unexpected changes, and establishing opportunities for regular communication within and across sectors. Study findings indicate that multidisciplinary approaches support health behavior change and provide insight into key issues to consider in developing and implementing such approaches in low-income communities.


Biogenesis of mitochondria. 18. A new class of cytoplasmically determined antibiotic resistant mutants in Saccharomyces cerevisiae.
New mutant yeasts resistant to the antibiotics chloramphenicol and mikamycin were isolated. They are mitochondrial mutants, characterized by several criteria as cytoplasmically determined. Biochemical studies show that amino acid incorporation into protein in vitro by mitochondria isolated from cells resistant or sensitive to mikamycin or chloramphenicol is inhibited by these antibiotics. Although aerobically-grown resistant strains of Saccharomyces cerevisiae are not affected by mikamycin or chloramphenicol, it is found that the mitochondrial protein-synthesizing system of anaerobically grown cells is inhibited in vivo. Cross resistance among the antibiotics chloramphenicol, mikamycin, erythromycin, lincomycin, carbomycin, and spiramycin is reported. All erythromycin resistant mutants, unlike the others, are resistant to erythromycin in vivo and in vitro. The results indicate that some of the cytoplasmic mutations (mikamycin and chloramphenicol resistance) are expressed at the mitochondrial membrane, whereas others (erythromycin resistance) possibly reflect changes in mitochondrial ribosomal proteins. We further suggest that conformational changes, either in the membranes or ribosomes, are likely to account for the observed antibiotic cross resistances.


Triploid atlantic salmon (Salmo salar L.) post-smolts accumulate prevalence more slowly than diploid salmon following bath challenge with salmonid alphavirus subtype 3.
Triploid Atlantic salmon (Salmo salar L.) may play an important role in the sustainable expansion of the Norwegian aquaculture industry. Therefore, the susceptibility of triploid salmon to common infections such as salmonid alphavirus (SAV), the causative agent of pancreas disease (PD), requires investigation. In this study, shortly after seawater transfer, diploid and triploid post-smolts were exposed to SAV type 3 (SAV3) using a bath challenge model where the infectious dose was 48 TCID50 ml-1 of tank water. Copy number analysis of SAV3 RNA in heart tissue showed that there was no difference in viral loads between the diploids and triploids. Prevalence reached 100% by the end of the 35-day experimental period in both infected groups. However, prevalence accumulated more slowly in the triploid group reaching 19% and 56% at 14 and 21 days post exposure (dpe) respectively. Whereas prevalence in the diploid group was 82% and 100% at the same time points indicating some differences between diploid and triploid fish. Both heart and pancreas from infected groups at 14 dpe showed typical histopathological changes associated with pancreas disease. Observation of this slower accumulation of prevalence following a natural infection route was possible due to the early sampling points and the exposure to a relatively low dose of virus. The triploid salmon in this study were not more susceptible to SAV3 than diploid salmon indicating that they could be used commercially to reduce the environmental impact of escaped farmed fish interbreeding with wild salmon. This is important information regarding the future use of triploid fish in large scale aquaculture where SAV3 is a financial threat to increased production.


Management of depression in people living with HIV/AIDS in Senegal: Acceptability, feasibility and benefits of group interpersonal therapy.
Depression is highly prevalent in people living with HIV (PLWH) and has negative consequences for daily life and care. We evaluated for the first time the acceptability, feasibility and benefits of group interpersonal therapy (IPT), combined with a task-shifting approach, to treat depression in PLWH in Senegal. PLWH with depression received group IPT following the World Health Organization protocol. Acceptability and feasibility criteria were defined from the literature data. The PHQ-9, the WHODAS, and the 12-item-stigma scale were used, pre- and post-treatment, including a 3-month follow-up, to assess depressive symptom severity, functioning and stigma, respectively. General linear mixed models were used to describe changes in outcomes over time. Of 69 participants, 60 completed group IPT. Refusal to enroll and dropout rates were 6.6 and 12.7%, respectively. Ninety-seven percent of participants attended at least seven out of eight sessions. Patients and facilitators endorsed group IPT, with willingness to recommend it. Depressive symptoms and disability improved drastically and sustainably. We showed that group IPT is well accepted and feasible in Senegal as treatment for depression in PLWH. Combined with a task-shifting approach, it can narrow the gap in mental health treatment. Implementation may be enhanced by refining patient identification procedures and increasing treatment accessibility.


Procedures for the GMP-Compliant Production and Quality Control of [18F]PSMA-1007: A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer.
Radiolabeled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection, we recently developed the fluorine-18-labelled PSMA-ligand [18F]PSMA-1007 as the next generation radiofluorinated Glu-ureido PSMA inhibitor after [18F]DCFPyL and [18F]DCFBC. Since radiosynthesis so far has been suffering from rather poor yields, novel procedures for the automated radiosyntheses of [18F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly-used radiosynthesisers. Using the novel one-step procedure, the [18F]PSMA-1007 was produced in good radiochemical yields ranging from 25 to 80% and synthesis times of less than 55 min. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and, at the same time, high yielding production pathway for the next generation PSMA radioligand [18F]PSMA-1007. Actually, it turned out that the radiosynthesis is as easily realised as the well-known [18F]FDG synthesis and, thus, transferable to all currently-available radiosynthesisers. Using the new procedures, the clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.


The multifaceted role of ATF4 in regulating glucose-stimulated insulin secretion.
Stress-inducible transcription factor ATF4 is essential for survival and identity of β-cell during stress conditions. However, the physiological role of ATF4 in β-cell function is not yet completely understood. To understand the role of ATF4 in glucose-stimulated insulin secretion (GSIS), β-cell-specific Atf4 knockout (βAtf4KO) mice were phenotypically characterized. Insulin secretion and mechanistic analyses were performed using islets from control Atf4f/f and βAtf4KO mice to assess key regulators for triggering and amplifying signals for GSIS. βAtf4KO mice displayed glucose intolerance due to reduced insulin secretion. Moreover, βAtf4KO islets exhibited a decrease in both the insulin content and first-phase insulin secretion. The analysis of βAtf4KO islets showed that ATF4 is required for insulin production and glucose-stimulated ATP and cAMP production. The results demonstrate that ATF4 contributes to the multifaceted regulatory process in GSIS even under stress-free conditions.


Genomic identification, expression profiling, and functional characterization of CatSper channels in the bovine.
Cation channels of sperm (CatSper) are sperm-specific calcium channels with identified roles in the regulation of sperm function in humans, mice, and horses. We sought to employ a comparative genomics approach to identify conserved CATSPER genes in the bovine genome, and profile their expression in reproductive tissue. We hypothesized that CATSPER proteins expressed in bull testicular tissue mediates sperm hyperactivation and their rheotactic response in the reproductive tract of the cow. Bioinformatic analysis identified all four known CATSPER genes (CATSPER 1-4) in the bovine genome, and profiling by quantitative real-time polymerase chain reaction identified site-specific variation in messenger ribonucleic acid (mRNA) expression for all four genes along the reproductive tract of the bull. Using a novel antibody against CATSPER 1, protein expression was confirmed and localized to the principal piece of bull sperm, in agreement with what has been reported in other species. Subsequent treatment of bull sperm with either the calcium chelator ethylene glycol tetraacetic acid; mibefradil, a specific blocker of CatSper channels in human sperm; or CATSPER1 antibody all significantly inhibited caffeine-induced hyperactivation and the rheotactic response, supporting the concept that the calcium influx occurs via CatSper channels. Taken together, the work here provides novel insights into expression and function of CatSper channels in bull testicular tissue and in the function of ejaculated sperm.


Cdk7 functions as a cdk5 activating kinase in brain.
Activity of Cdk5, which is essential for CNS development, depends on its association with p35 (or truncated p25) or p39, but the regulatory mechanisms whereby Cdk5 is activated have not yet been fully elucidated. Studies on PC12 cells showed that Cdk5/p25 activity is modulated by an unidentified kinase that phosphorylates Cdk5 at Ser159 and enhances its kinase activity (Sharma et al., 1999 PNAS USA 96,11156). In this study, we have partially purified a bovine brain enzyme that can phosphorylate the Cdk5(149-163) peptide but not the Cdk5(149-163)A159 peptide. The enzyme, which contains Cdk7, cyclin H, and Mat1, specifically phosphorylates Ser159 of Cdk5(149-163) and enhances Cdk5/p25 activity. The active Cdk7-containing enzyme also phosphorylates and activates wt Cdk5 but not mutated Cdk5(Ser159Ala). Likewise, Cdk7 or cyclin H immunoprecipitate from mouse brain specifically phosphorylates wt Cdk5 at Ser159 and enhances Cdk5/p25 activity. Conversely, blocked Cdk7 immunoprecipitate does not phosphorylate nor activate Cdk5. In addition, the Cdk7 substrate, CTD of RNAPII, causes a dose-dependent decline in Cdk5 activation by Cdk7. These findings indicate that Cdk7 functions as a Cdk5 activating kinase in brain. Indeed, elevated Cdk5 activity in the developing E18 mouse brain coincides with increased Cdk7 kinase activity.


Consequences of amblyopia on education, occupation, and long term vision loss.
To describe the effect of amblyopia on education, occupation, and 5 year incident vision loss. 3654 participants aged 49 years or older participated in the Blue Mountains Eye Study (BMES I, 1992-4) and 2335 (75.1% of survivors) were re-examined (BMES II, 1997-9). All participants underwent detailed eye examination. Amblyopia, defined as best corrected visual acuity of less than or equal to 6/9 and not attributable directly to any underlying structural abnormality of the eye or the visual pathway, was identified in 118 participants (3.2%) in BMES I, of whom 73 were re-examined in BMES II. Occupation and educational classifications used definitions of the Australian Bureau of Statistics. The mean age of people with amblyopia seen at baseline was 67.0 years. Amblyopia did not affect lifetime occupational class (p = 0.5), but fewer people completed higher university degrees (p = 0.05). In people with amblyopia, there was an increased risk of 5 year incident visual impairment in the better seeing eye worse than 6/12, relative risk (RR) 2.7, 95% confidence interval (CI) 1.6 to 4.6. One of 11 (9.1%) people with amblyopia showed significant improvement in visual acuity in the poorer seeing eye after a two line (10 logMAR letter) vision loss in the better seeing eye. This study further documents the longitudinal history of amblyopia using population based data.


Transcatheter Aortic Valve Implantation in Patients at Extremely High Risk of Perioperative Mortality.
Transcatheter procedures are considered the therapy of choice for high-risk patients who are not eligible for surgical aortic valve replacement. Although its utility is debated, the logistic EuroSCORE I is still the most frequently used risk calculator for cardiac surgery in Europe, and was used in the present study to identify patients with an extremely high risk of predicted perioperative mortality. This single-centre study included 319 consecutive patients who underwent transapical or transaortic transcatheter aortic valve implantation (TAVI) between September 2008 and December 2012. Combined hybrid procedures and transfemoral TAVI patients were excluded. Those patients predicted to have an excessively high risk of perioperative mortality (EuroSCORE >40%, n = 90) were compared to those with a lower calculated risk (EuroSCORE <40%, n = 229) with respect to perioperative complications, short-term-mortality and major adverse cardiac and cerebrovascular events. The 30-day mortality was 12.2% (n = 11) in the extremely high-risk group, and 6.6% (n = 15) in the lower-risk group (p = 0.08). There were no significant differences in the stroke rate (3.3% versus 0.4%, p = 0.07) or the incidence of acute kidney injury stage 3 (11.1% versus 5.2%, p = 0.32). The establishment of cardiopulmonary bypass (3.9% versus 11.1%, p = 0.02), conversion to sternotomy (1.3% versus 5.6%, p = 0.04), mean ventilation time (15.2 h versus 43.5 h, p = 0.007) and length of intensive care unit stay (2.9 days versus 6.8 days, p <0.001) were all significantly lower in the lower-risk group. The data acquired verified that TAVI is a safe procedure, even in patients with an extremely high predicted risk of perioperative mortality and major adverse cardiac and cerebrovascular events. Furthermore, the analysis substantiated the need for individualized risk evaluation.