Multi-scale ensemble properties of the Escherichia coli RNA degradosome.
In organisms from all domains of life, multi-enzyme assemblies play central roles in defining transcript lifetimes and facilitating RNA-mediated regulation of gene expression. An assembly dedicated to such roles, known as the RNA degradosome, is found amongst bacteria from highly diverse lineages. About a fifth of the assembly mass of the degradosome of Escherichia coli and related species is predicted to be intrinsically disordered - a property that has been sustained for over a billion years of bacterial molecular history and stands in marked contrast to the high degree of sequence variation of that same region. Here, we characterize the conformational dynamics of the degradosome using a hybrid structural biology approach that combines solution scattering with ad hoc ensemble modelling, cryo-electron microscopy, and other biophysical methods. The E. coli degradosome can form punctate bodies in vivo that may facilitate its functional activities, and based on our results, we propose an electrostatic switch model to account for the propensity of the degradosome to undergo programmable puncta formation.


Lysozyme in water-acetonitrile mixtures: Preferential solvation at the inner edge of excess hydration.
Preferential solvation/hydration is an effective way for regulating the mechanism of the protein destabilization/stabilization. Organic solvent/water sorption and residual enzyme activity measurements were performed to monitor the preferential solvation/hydration of hen egg-white lysozyme at high and low water content in acetonitrile at 25 °C. The obtained results show that the protein destabilization/stabilization depends essentially on the initial hydration level of lysozyme and the water content in acetonitrile. There are three composition regimes for the dried lysozyme. At high water content, the lysozyme has a higher affinity for water than for acetonitrile. The residual enzyme activity values are close to 100%. At the intermediate water content, the dehydrated lysozyme has a higher affinity for acetonitrile than for water. A minimum on the residual enzyme activity curve was observed in this concentration range. At the lowest water content, the organic solvent molecules are preferentially excluded from the dried lysozyme, resulting in the preferential hydration. The residual catalytic activity is ∼80%, compared with that observed after incubation in pure water. Two distinct schemes are operative for the hydrated lysozyme. At high and intermediate water content, lysozyme is preferentially hydrated. However, in contrast to the dried protein, at the intermediate water content, the initially hydrated lysozyme has the increased preferential hydration parameters. At low water content, the preferential binding of the acetonitrile molecules to the initially hydrated lysozyme was detected. No residual enzyme activity was observed in the water-poor acetonitrile. Our data clearly show that the initial hydration level of the protein macromolecules is one of the key factors that govern the stability of the protein-water-organic solvent systems.


Flexible cellulose and ZnO hybrid nanocomposite and its UV sensing characteristics.
This paper reports the synthesis and UV sensing characteristics of a cellulose and ZnO hybrid nanocomposite (CEZOHN) prepared by exploiting the synergetic effects of ZnO functionality and the renewability of cellulose. Vertically aligned ZnO nanorods were grown well on a flexible cellulose film by direct ZnO seeding and hydrothermal growing processes. The ZnO nanorods have the wurtzite structure and an aspect ratio of 9 ~ 11. Photoresponse of the prepared CEZOHN was evaluated by measuring photocurrent under UV illumination. CEZOHN shows bi-directional, linear and fast photoresponse as a function of UV intensity. Electrode materials, light sources, repeatability, durability and flexibility of the prepared CEZOHN were tested and the photocurrent generation mechanism is discussed. The silver nanowire coating used for electrodes on CEZOHN is compatible with a transparent UV sensor. The prepared CEZOHN is flexible, transparent and biocompatible, and hence can be used for flexible and wearable UV sensors.


Effects of cerium oxide nanoparticles on differentiated/undifferentiated human intestinal Caco-2 cells.
Since ingestion constitute one of the main routes of nanoparticles (NPs) exposure, intestinal cells seems to be a suitable choice to evaluate their potential harmful effects. Caco-2 cells, derived from a human colon adenocarcinoma, have the ability to differentiate forming consistent cell monolayer structures. For these reasons Caco-2 cells, both in their undifferentiated or differentiated state, are extendedly used. We have used well-structured monolayers of differentiated Caco-2 cells, as a model of intestinal barrier, to evaluate potential harmful effects associated to CeO2NPs exposure via ingestion. Different parameters such as cell toxicity, monolayer integrity and permeability, cell internalization, translocation through the monolayer, and induction of DNA damage were evaluated. No toxic effects of CeO2NPs were observed, independently of the differentiated state of the Caco-2 cells. In the same way, no effects on the monolayer integrity/permeability were observed. Although important cell uptake was demonstrated in undifferentiated cells (by using confocal microscopy), CeO2NPs remained mostly attached to the apical membrane in the differentiated cells. In spite of this apparent lack of uptake in differentiated cells, translocation of CeO2NPs to the basolateral chamber was observed by using confocal microscopy. Finally no genotoxic effects were observed when the comet assay was used, although decreases in the levels of oxidized bases were observed, supporting the antioxidant role of CeO2NPs.


Epidermoid cyst of the spleen: case report.
The classification, incidence, and clinical, radiologic, and scintigraphic findings of benign nonparasitic splenic cysts are presented with a case report of epidermoid cyst of the spleen.


Atypical Ductal Hyperplasia and Those Bordering on Ductal Carcinoma In Situ Should Be Included in the Active Surveillance Clinical Trials.
Women with atypical ductal hyperplasia (ADH), unlike those with ductal carcinoma in situ (DCIS), are denied eligibility for active surveillance clinical trials. We applied the inclusion criteria of the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial to the cases of women (n = 165) at the Roswell Park Cancer Institute who had a diagnosis of ADH, ADH bordering on DCIS, or low- to intermediate-grade DCIS on core biopsy taken during screening mammography. Upgrade of lesions to high risk was based on invasive carcinoma, high-grade DCIS, or DCIS with comedo necrosis. In total, nine (5.5%) lesions were upgraded: two (1.7%) reported ADH, one (5.9%) reported ADH bordering on DCIS, and six (19.4%) reported DCIS (P = .002); and two (1.6%) reclassified ADH vs seven (17.1%) reclassified DCIS (P < .001). In multivariate analysis, only increased number of foci had the potential to predict high risk (odds ratio: 1.39; P = .06). We conclude that ADH and ADH bordering on DCIS have lower upgrade rates than DCIS. We recommend opening an active surveillance clinical trial for women with these diagnoses.


Forks on the Run: Can the Stalling of DNA Replication Promote Epigenetic Changes?
Built of DNA polymerases and multiple associated factors, the replication fork steadily progresses along the DNA template and faithfully replicates DNA. This model can be found in practically every textbook of genetics, with the more complex situation of chromatinized DNA in eukaryotes often viewed as a variation. However, the replication-coupled disassembly/reassembly of chromatin adds significant complexity to the whole replication process. During the course of eukaryotic DNA replication the forks encounter various conditions and numerous impediments. These include nucleosomes with a variety of post-translational modifications, euchromatin and heterochromatin, differentially methylated DNA, tightly bound proteins, active gene promoters and DNA loops. At such positions the forks slow down or even stall. Dedicated factors stabilize the fork and prevent its rotation or collapse, while other factors resolve the replication block and facilitate the resumption of elongation. The fate of histones during replication stalling and resumption is not well understood. In this review we briefly describe recent advances in our understanding of histone turnover during DNA replication and focus on the possible mechanisms of nucleosome disassembly/reassembly at paused replication forks. We propose that replication pausing provides opportunities for an epigenetic change of the associated locus.


Quality of life and mental health among parents of children with cerebral palsy: the influence of self-efficacy and coping strategies.
To explore the quality of life and mental health of caregivers of children with cerebral palsy and to examine the impact of self-efficacy and coping strategies on these outcomes. Few studies analyse the impact of caring for a child with cerebral palsy on the caregivers' quality of life besides mental health. Also, less attention has been paid to the influence of caregiver's personal resources like self-efficacy or coping strategies on how they adjust to the child's illness and the care situation. Cross-section correlational design. Sixty two parents of children with cerebral palsy completed measures to assess the quality of life (i.e. physical, environmental and social relationships), mental health (i.e. general mental health, depression and anxiety), self-efficacy and coping strategies. Parents of children with cerebral palsy had, in general terms, low levels of quality of life and mental health. Self-efficacy was related to most of the outcomes, whereas any of the coping strategies assessed was significantly related to the outcomes. Quality of life and mental health can be affected in caregivers of children with CP. Personal resources like self-efficacy also need attention as they can help in the understanding of the differences in these outcomes and the design of effective interventions. RELEVANCE OF CLINICAL PRACTICE: Self-efficacy should be a key element in interventions addressed to parents of children with CP to elicit a process of empowerment that can improve the well-being of the family as a whole.


[Pathogenicity of West Nile virus: molecular markers].
The review describes the phenotypic properties, structure, and expression pattern of West Nile virus genome (Flaviviridae, Flavivirus, Japanese encephalitis antigenic complex), as well as the clinical picture and pathogenesis of its etiologically related disease West Nile fever. It also analyzes the available data on the impact of genetic mutations in the genome on the biological properties of the virus.


[Homologous plasma cross-circulation on galactosamine induced hepatic failure rats].
Plasma cross-circulation which resembles plasma exchange clinically was carried out in between galactosamine (GalN) treated hepatic failure rats and normal rats. Twenty-four hours after the injection of GalN, plasma cross-circulation was performed at a plasma flow rate of 0.1 ml/min for 6 hours. In eighteen hours after the completion of a procedure, survival rate was 75% (6 out of 8 survived) in GalN injected rats treated with plasma cross-circulation, as compared to 40% (4 out of 10 survived) in GalN injected rats treated with sham-circulation. State 3 oxygen consumption and ATP synthesis in the liver mitochondrial respiratory function, and ATP and total adenine nucleotide contents in the liver in the former group were significantly higher than those in the latter group at the time of sacrifice of the survived animals. These appear to suggest that plasma cross-circulation enhances mitochondrial phosphorylative activity in the liver and may contribute higher survival rate of the rats. Plasma exchange using a large amount of fresh plasma, therefore, would be effective for the treatment of acute liver failure in its early stage.


Nuclear epoxide hydrolase in the human fetal and adult liver.
The epoxide hydrolase activity with styrene oxide as substrate was investigated in the nuclear fraction of human fetal and adult liver specimens. All investigated liver fractions catalyzed the hydration of styrene oxide and the average epoxide hydrolase activities were 0.37 and 1.90 nmol/min/mg protein in fetal and adult specimens, respectively. The enzyme followed Michaelis-Menten kinetics in fetal nuclear fraction and biphasic kinetics in adult livers. The nuclear/microsomal enzyme activity ratios of epoxide hydrolase were 0.09 and 0.11 for fetal and adult livers, respectively.


Calculated organ doses using Monte Carlo simulations in a reference male phantom undergoing HDR brachytherapy applied to localized prostate carcinoma.
The aim of this study was to obtain equivalent doses in radiosensitive organs (aside from the bladder and rectum) when applying high-dose-rate (HDR) brachytherapy to a localized prostate carcinoma using (60)Co or (192)Ir sources. These data are compared with results in a water phantom and with expected values in an infinite water medium. A comparison with reported values from proton therapy and intensity-modulated radiation therapy (IMRT) is also provided. Monte Carlo simulations in Geant4 were performed using a voxelized phantom described in International Commission on Radiological Protection (ICRP) Publication 110, which reproduces masses and shapes from an adult reference man defined in ICRP Publication 89. Point sources of (60)Co or (192)Ir with photon energy spectra corresponding to those exiting their capsules were placed in the center of the prostate, and equivalent doses per clinical absorbed dose in this target organ were obtained in several radiosensitive organs. Values were corrected to account for clinical circumstances with the source located at various positions with differing dwell times throughout the prostate. This was repeated for a homogeneous water phantom. For the nearest organs considered (bladder, rectum, testes, small intestine, and colon), equivalent doses given by (60)Co source were smaller (8%-19%) than from (192)Ir. However, as the distance increases, the more penetrating gamma rays produced by (60)Co deliver higher organ equivalent doses. The overall result is that effective dose per clinical absorbed dose from a (60)Co source (11.1 mSv/Gy) is lower than from a (192)Ir source (13.2 mSv/Gy). On the other hand, equivalent doses were the same in the tissue and the homogeneous water phantom for those soft tissues closer to the prostate than about 30 cm. As the distance increased, the differences of photoelectric effect in water and soft tissue, and appearance of other materials such as air, bone, or lungs, produced variations between both phantoms which were at most 35% in the considered organ equivalent doses. Finally, effective doses per clinical absorbed dose from IMRT and proton therapy were comparable to those from both brachytherapy sources, with brachytherapy being advantageous over external beam radiation therapy for the furthest organs. A database of organ equivalent doses when applying HDR brachytherapy to the prostate with either (60)Co or (192)Ir is provided. According to physical considerations, (192)Ir is dosimetrically advantageous over (60)Co sources at large distances, but not in the closest organs. Damage to distant healthy organs per clinical absorbed dose is lower with brachytherapy than with IMRT or protons, although the overall effective dose per Gy given to the prostate seems very similar. Given that there are several possible fractionation schemes, which result in different total amounts of therapeutic absorbed dose, advantage of a radiation treatment (according to equivalent dose to healthy organs) is treatment and facility dependent.


[Effectiveness of a nutritional education program in lowering blood cholesterol levels in a public health center].
An educational program for persons found to have high blood cholesterol during health examinations at the Nerima Public Health Center was begun in April, 1989. This program was differed from the usual program in two areas. First, new educational material was developed consisting of a check list of 30 items to assess eating patterns. By checking these items, participants could gain an understanding of what they should change in their eating behavior. Secondly, the table of restricted foods was not used. Participants were advised to achieve healthy eating patterns and followed up with a nutritional consultation that was held after three months, at which time they were interviewed regarding compliance and had their blood cholesterol levels measured. The effectiveness of the new educational program and the relationship between achievement of healthy eating patterns and reduction in blood cholesterol levels were analyzed. The main results were as follows: 1) In subjects (n = 79) who received the new education program in 1989-1990, serum cholesterol levels showed significant reduction, as compared with controls (n = 38) who received the usual education program in 1988-1989. 2) Subjects were divided into three groups according to their changes in serum cholesterol levels,--normalized, improved and unimproved--and the number of items complied with were counted for analysis. The mean score of compliance was highest in the normalized group with significant difference between the normalized and the unimproved groups. 3) The items of the high compliance score in the normalized group were in order of high score "to decrease high-fat meats", "to decrease cakes", "to choose lean meats and poultry without skin" and "to eat vegetables at every meal".


Characteristics of electron heat transport of plasma with an electron internal-transport barrier in the large helical device.
Associated with the transition from ion root to electron root, an electron internal transport barrier (ITB) appears in the large helical device, when the heating power of electron cyclotron resonance heating exceeds the threshold power. The incremental thermal diffusivity of electron heat transport chi(inc)(e) in the ITB plasma is much lower than that in the plasma with the heating power below the threshold, and the thermal diffusivity chi(e) decreases with increasing of heating power [dchi(e)/d(P/n(e))<0] in helical ITB plasmas.


Study on protecting effects of baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis.
To investigate the protective effects and mechanisms of baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). The SAP rat models were prepared and randomly assigned to the model control group, baicalin treated group, and octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and caspase-3, and changes of apoptotic indexes. Rat survival at 12 h, expression levels of Bax, caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. Both baicalin and octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, caspase-3 protein, and inducing apoptosis.


Schwann Cell-Mediated Preservation of Vision in Retinal Degenerative Diseases via the Reduction of Oxidative Stress: A Possible Mechanism.
After injury to the central nervous system (CNS), regeneration is often inadequate, except in the case of remyelination. This remyelination capacity of the CNS is a good example of a stem/precursor cell-mediated renewal process. Schwann cells have been found to act as remyelinating agents in the peripheral nervous system (PNS), but several studies have highlighted their potential role in remyelination in the CNS too. Schwann cells are able to protect and support retinal cells by secreting growth factors such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and basic fibroblast growth factor. Retinal degenerative diseases can be highly debilitating, and they are a major concern in countries with an ageing populations. One of the leading causes of permanent loss of vision in the West is a retinal degenerative disease known as age-related macular degeneration (AMD). In the United States, nearly 1.75 million people over the age of 40 have advanced AMD, and it is estimated that this number will increase to approximately 3 million people by 2020. One of the most common pathways involved in the initiation and development of retinal diseases is the oxidative stress pathway. In patients with diabetes, Schwann cells have been shown to be able to secrete large amounts of antioxidant enzymes that protect the PNS from the oxidative stress that results from fluctuations in blood glucose levels. This antioxidant ability may be involved in the mechanism by which Schwann cells are able to promote reconstruction in the CNS, especially in individuals with retinal injuries and degenerative diseases.


Realistic simulation of virtual multi-scale, multi-modal patient trajectories using Bayesian networks and sparse auto-encoders.
Translational research of many disease areas requires a longitudinal understanding of disease development and progression across all biologically relevant scales. Several corresponding studies are now available. However, to compile a comprehensive picture of a specific disease, multiple studies need to be analyzed and compared. A large number of clinical studies is nowadays conducted in the context of drug development in pharmaceutical research. However, legal and ethical constraints typically do not allow for sharing sensitive patient data. In consequence there exist data "silos", which slow down the overall scientific progress in translational research. In this paper, we suggest the idea of a virtual cohort (VC) to address this limitation. Our key idea is to describe a longitudinal patient cohort with the help of a generative statistical model, namely a modular Bayesian Network, in which individual modules are represented as sparse autoencoder networks. We show that with the help of such a model we can simulate subjects that are highly similar to real ones. Our approach allows for incorporating arbitrary multi-scale, multi-modal data without making specific distribution assumptions. Moreover, we demonstrate the possibility to simulate interventions (e.g. via a treatment) in the VC. Overall, our proposed approach opens the possibility to build sufficiently realistic VCs for multiple disease areas in the future.


Schistosomiasis associated bladder carcinoma expression of cytokeratin.
Twenty patients with bladder carcinoma (14 transitional cell carcinoma and six squamous cell carcinoma) and ten controls of (four with bilharzial lesions, three without and three with metaplasia and dysplasia) were subjected to immunocytochemical and immunohistochemical studies. Bladder and urine samples examination were carried out with the high molecular weight cytokeratin and broad spectrum keratin antibodies using peroxidase anti-peroxidase. Cytokeratins of high molecular weight were expressed in all squamous cancer while broad spectrum keratin was positive in 83.3%. The transitional cell carcinoma was positive in 50% with both cytokeratin and broad spectrum keratin. Urine shedded were positive in 83.3% and 66.7% of squamous cell carcinoma with high molecular weight cytokeratin and broad spectrum keratin respectively. However, each of them was positive in 50% of transitional carcinoma, and negative with non-malignant cases except with metaplasia and dysplasia.


Toll-like receptors are part of the innate immune defense system of sponges (demospongiae: Porifera).
During evolution and with the emergence of multicellular animals, the need arose to ward off foreign organisms that threaten the integrity of the animal body. Among many different receptors that participate in the recognition of microbial invaders, toll-like receptors (TLRs) play an essential role in mediating the innate immune response. After binding distinct microbial components, TLRs activate intracellular signaling cascades that result in an induced expression of diverse antimicrobial molecules. Because sponges (phylum Porifera) are filter feeders, they are abundantly exposed to microorganisms that represent a potential threat. Here, we describe the identification, cloning, and deduced protein sequence from 3 major elements of the poriferan innate response (to bacterial lipopeptides): the TLR, the IL-1 receptor-associated kinase-4-like protein (IRAK-4l), and a novel effector caspase from the demosponge Suberites domuncula. Each molecule shares significant sequence similarity with its homologues in higher Metazoa. Sequence homologies were found in particular within the family-specific domains toll/interleukin-1 receptor/resistance (TLR family), Ser/Thr/Tyr kinase domain (IRAK family), and CASc (caspase family). In addition, in situ hybridization and immunohistological analyses revealed an abundance of SDTLR (TLR) transcripts in epithelial layers of the sponge surface (exopinacoderm and endopinacoderm). Furthermore, it is shown that both SDTLR and SDIRAK-4 like (IRAK) are expressed constitutively, regardless of treatment with synthetic triacyl lipopeptide Pam(3)Cys-Ser-(Lys)(4). In contrast, SDCASL (caspase) expression is highly Pam(3)Cys-Ser-(Lys)(4) inducible. However, blocking of the lipopeptide with recombinant TLR prior to its application completely prevented the induced expression of this poriferan caspase. These results underscore that the phylogenetically oldest extant metazoan phylum is provided already with the signaling pathways of the antimicrobial host-defense system of Metazoa.


Computer-assisted drug discovery of potential natural inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase through a multi-phase in silico approach.
The COVID-19 pandemic has led to significant loss of life and economic disruption worldwide. Currently, there are limited effective treatments available for this disease. SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp) has been identified as a potential target for drug development against COVID-19. Natural products have been shown to possess antiviral properties, making them a promising source for developing drugs against SARS-CoV-2. The objective of this study is to identify the most effective natural inhibitors of SARS-CoV-2 RdRp among a set of 4924 African natural products using a multi-phase in silico approach. The study utilized remdesivir (RTP), the co-crystallized ligand of RdRp, as a starting point to select compounds that have the most similar chemical structures among the examined set of compounds. Molecular fingerprints and structure similarity studies were carried out in the first part of the study. The second part of the study included molecular docking against SARS-CoV-2 RdRp (PDB ID: 7BV2) and Molecular Dynamics (MD) simulations including the calculation of RMSD, RMSF, Rg, SASA, hydrogen bonding, and PLIP. Moreover, the calculations of Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) Lennard-Jones and Columbic electrostatic interaction energies have been conducted. Additionally, in silico ADMET and toxicity studies were performed to examine the drug likeness degrees of the selected compounds. Eight compounds were identified as the most effective natural inhibitors of SARS-CoV-2 RdRp. These compounds are kaempferol 3-galactoside, kaempferol 3-O-β-D-glucopyranoside, mangiferin methyl ether, luteolin 7-O-β-D-glucopyranoside, quercetin-O-β-D-3-glucopyranoside, 1-methoxy-3-indolylmethyl glucosinolate, naringenin, and asphodelin A 4'-O-β-D-glucopyranoside. The results of this study provide valuable information for the development of natural product-based drugs against COVID-19. However, the elected compounds should be further studied in vitro and in vivo to confirm their efficacy in treating COVID-19.


Implementation of a military-derived damage-control resuscitation strategy in a civilian trauma center decreases acute hypoxia in massively transfused patients.
Recent military experience supports a paradigm shift in shock resuscitation to damage-control resuscitation (DCR), which emphasizes a plasma-rich and crystalloid-poor approach to resuscitation. The effect of DCR on hypoxia after massive transfusion is unknown. We hypothesized that implementation of a military-derived DCR strategy in a civilian setting would lead to decreased acute hypoxia. A DCR strategy was implemented in 2007. We retrospectively reviewed patients receiving trauma surgeon operative intervention and 10 or more units of packed red blood cells (pRBCs) within 24 hours of injury at an adult Level I trauma center from 2001 to 2010. Demographic data, blood requirements, and PaO₂/FIO₂ ratios were analyzed. To evaluate evolving resuscitation strategies, we fit linear trend models to continuous variables and tested their slopes for statistical significance. Two hundred sixteen patients met the study criteria, with a mean age of 35 ± 1.1 years and Injury Severity Score (ISS) of 31 ± 9.0. Of the patients, 80% were male, and 52% sustained penetrating injuries. Overall mortality was 32%. Overall mean pRBC and fresh frozen plasma (FFP) units infused in 24 hours were 23.2 ± 1.1 and 18.6 ± 1.1, respectively. Trends for patient age, sex, mechanism of injury, ISS, highest positive end-expiratory pressure, and mean total pRBC transfused over 24 hours were not statistically different from zero. An increasing trend in FFP and platelets transfused during the first 24 hours (p < 0.0001, p = 0.04, respectively) and a decrease in the pRBC/FFP ratio (p < 0.0001) were found. The amount of crystalloid infused during the initial 24 hours decreased with time (p < 0.0001). The lowest PaO₂/FIO₂ ratio recorded during the initial 24 hours increased during the study period (p = 0.01), indicating a statistically significant reduction in hypoxia. A military-derived DCR strategy can be implemented in the civilian setting. DCR led to significant increases in FFP transfusion, decreases in crystalloid use, and acute hypoxia.


The risk of multiple addictions. Guidelines for assessing a woman's alcohol and drug use.
Psychotropic drugs have been overly prescribed for women of all ages for all manner of symptoms. Patients' and physicians' expectations about appropriate diagnosis and treatment, combined with the relative invisibility of women's alcohol and legal and illicit drug use, can lead to quick but temporary prescription solutions that may put women at risk for multiple addictions. This is a special problem for adolescent, minority, and elderly women, about whom we know little yet hold strong stereotypes. Moreover, while prescriptions may alleviate patients' symptoms, they do little to correct the underlying situation. Physicians are encouraged to review their prescribing habits and to learn more about their women patients' use of alcohol, cigarettes, previously prescribed medications, and recreational drugs, as well as a tendency to self-medicate. Physicians should also have available alternative strategies to prescribing psychotropic drugs.


[Chemo-radiotherapy for head and neck cancer].
Many randomized trials have investigated the effect on survival of induction chemotherapy; none however, has demonstrated improved survival. A study of the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated the feasibility of induction CDDP/5-FU plus surgical salvage as an alternative to initial laryngectomy, but it did not include a radiation-alone treatment arm. Thus, a three-arm trial (R 91-11) was needed to compare the regimen of induction chemotherapy plus surgical salvage treatment with radiation alone and with concurrent chemo-radiation, to determine whether the addition of chemotherapy led to better results than conventional radiation alone. R 91-11 data revealed that concurrent chemo-radiation significantly increased the time to laryngectomy and chemotherapy suppressed distant metastasis, but there was no difference in overall survival. Single-agent docetaxel is known to induce a response in 22-45% of patients with recurrent squamous cell cancer of the head and neck. When used in combination with CDDP, response rates of between 40 and 54% have been reported. Increased expression the epidermal growth factor receptor (EGFR) is reported in head and neck cancer. Anti-EGFR monoclonal antibody is associated with decreased cell proliferation, inhibition of metastasis and angiogenesis, and it has a synergistic effect with chemotherapy or radiotherapy. It is hoped that further advances will lead to greater realization of the therapeutic potential of these compounds as anticancer agents.


Role of nod2 in the response of macrophages to toll-like receptor agonists.
Nod2 (CARD15) is a macrophage-specific protein containing two CARD domains, a large nucleotide binding domain and leucine-rich repeats. Human genetic studies have linked mutations in NOD2/CARD15 with Crohn's disease, although the mechanisms involved are unknown. However, Nod2 has been proposed to directly bind bacterial lipopolysaccharide (LPS) and subsequently act as an activator of NF-kappaB via the association of the CARD domains with Rip2/RICK/CARDIAK. This is hypothesized to constitute a pathogen recognition pathway distinct from Toll-like receptor 4-mediated recognition of LPS. Using targeted mutagenesis, we introduced a mutation to delete the CARD domains of mouse Nod2. Mice lacking Nod2 were indistinguishable from controls and showed no signs of intestinal pathology. Macrophages responded normally to multiple Toll-like receptor agonists in terms of NF-kappaB target activation, mitogen-activated protein kinase activation, and cytokine secretion. However, Nod2(-/-) mice were significantly protected in endotoxin challenge experiments, and Nod2(-/-) macrophages were refractory to muramyl dipeptide stimulation. These results argue that Nod2 does not play an essential, nonredundant role in the response of macrophages to bacterial products but rather plays unexpected roles in regulating systemic responses to pathogens.


Centrosome- and Golgi-Localized Protein Kinase N-Associated Protein Serves As a Docking Platform for Protein Kinase A Signaling and Microtubule Nucleation in Migrating T-Cells.
Centrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP), also known as AKAP450, is a cytosolic scaffolding protein involved in the targeted positioning of multiple signaling molecules, which are critical for cellular functioning. Here, we show that CG-NAP is predominantly expressed in human primary T-lymphocytes, localizes in close proximity (<0.2 μm) with centrosomal and Golgi structures and serves as a docking platform for Protein Kinase A (PKA). GapmeR-mediated knockdown of CG-NAP inhibits LFA-1-induced T-cell migration and impairs T-cell chemotaxis toward the chemokine SDF-1α. Depletion of CG-NAP dislocates PKARIIα, disrupts centrosomal and non-centrosomal microtubule nucleation, causes Golgi fragmentation, and impedes α-tubulin tyrosination and acetylation, which are important for microtubule dynamics and stability in migrating T-cells. Furthermore, we show that CG-NAP coordinates PKA-mediated phosphorylation of pericentrin and dynein in T-cells. Overall, our findings provide critical insights into the roles of CG-NAP in regulating cytoskeletal architecture and T-cell migration.


Healing of cervical epithelium after laser treatment of cervical intraepithelial neoplasia.
The recognition that only a minority of cervical premalignant lesions progress to invasion, and the increasing incidence of these lesions in young women, has led to a more conservative approach in the treatment of cervical intraepithelial neoplasia. One such method uses the carbon dioxide laser but inadequate length of follow-up has prevented a prediction of risk of recurrence. Observations made in this study on the speed of healing, source of new epithelium, maturation of the epithelium and the absence of herpes nucleic acid suggest that this risk is low.


Combined effect of diazepam and polystyrene microplastics on the social behavior of medaka (Oryzias latipes).
The combined effect of microplastics and pharmaceuticals on aquatic organisms is an issue of concern. In this laboratory study, we evaluated the combined effect of polystyrene microplastics (2-μm diameter) and diazepam on the social behavior of medaka (Oryzias latipes) by using the shoaling behavior test with five treatment groups: solvent control, polystyrene microplastics exposure (0.04 mg/L), low-concentration diazepam exposure (0.03 mg/L), high-concentration diazepam exposure (0.3 mg/L), and polystyrene microplastics and low-concentration diazepam co-exposure. After 7 days of exposure, the shoal-leaving behavior of the high-concentration diazepam exposure group (8.9 ± 8.3 counts/medaka) and the co-exposure group (6.8 ± 6.7 counts/medaka) was significantly greater than that in the solvent control group (1.8 ± 2.6 counts/medaka). Even after 5 days of recovery, medaka in the co-exposure group left the shoal more often (7.3 ± 5.0 counts/medaka) than those in the solvent control group (2.6 ± 2.6 counts/medaka), whereas the shoal-leaving behavior in other exposure groups, except for the high-concentration diazepam exposure group, was restored. Our findings show that the combined effects of diazepam and polystyrene microplastics suppressed medaka social behavior, suggesting that the presence of microplastics can enhance the adverse effects of pollutants on the social behavior of aquatic organisms.


Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2.
Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of acute liver failure (ALF) in some countries including the United States and with few available treatments. Isorhamnetin is a bioflavonoid that is found in medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L. with promising potential to regulate inflammatory responses. In this study, we evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI and analyzed further the involvement of oxidative stress and inflammation-associated factors. Male C57BL/6 mice were given isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at 48, 24, and 1 h before APAP administration (300 mg/kg b.w., i.p.). Functional indicators of liver injury were measured as well as analysis of oxidative stress- and inflammation-associated indices and liver histopathology was also conducted. Isorhamnetin at the higher dose of 100 mg/kg significantly lowered serum levels of ALT, ALP, and AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3, caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity, sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These findings show protective effect of isorhamnetin against acetaminophen-induced liver injury through reducing oxidative stress, inflammation, and pyroptosis which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.


[Investigations of the antihypertensive long-term action of candesartan cilexetil in different dosages under the influence of therapy-free intervals].
In a randomized, phase IV clinical study with 4 parallel treatment arms, the long-lasting treatment effect of candesartan cilexetil (CAS 145040-37-5, CC, Blopress) was to be demonstrated for a repeated therapy-free interval of 48 h in the dosages 8 and 16 mg with or without hydrochlorothiazide 12.5 mg (CAS 58-93-5, HCT; 4 groups totally). The reason for this design was the known possibility of missed tablet doses in the patients' daily practice leading to a not always sufficient lowering of blood pressure in essential hypertension. Therefore, the intake of the daily tablet dose was intentionally omitted twice (after 6 and 8 weeks) during the 8-week study treatment period. Primary efficacy variable was the comparison of blood pressure lowering before and after the first 48-hour therapy-free interval following a 6-week treatment period. The confirmatory analysis was done on the basis of paired t-tests and the Bonferroni-Holm "step-down procedure" for the systolic and diastolic results in each of the four treatment groups. Secondary variables were the efficacy 24 and 48 h after the last tablet intake following a 6- and 8-week treatment period, the blood pressure normalization rate and the tolerability. 312 out-patients from 46 study centers in Germany with mild or moderate essential hypertension strictly treated according to the protocol requirements were evaluated in terms of all primary and secondary study parameters. The patient allocation to the 4 treatment arms as well as the conditions at study start concerning demographic data, physical investigation, patient history, ECG, concomitant diseases/therapy and baseline values of blood pressure were well comparable between the four groups. The antihypertensive therapy with CC showed the expected clear effect on blood pressure lowering in 312 per-protocol treated patients with in addition an increase for the higher dosages and for the combination with HCT. The mean rate of lowering (systolic/diastolic) after 24 h for all treatment groups together was 14.5/8.1 mmHg after 6 weeks and 17.3/9.5 mmHg after 8 weeks of therapy. The described antihypertensive blood lowering effect could be maintained in nearly 100% diastolic and 100% systolic values for the first 48-hour therapy-free interval after 6 weeks and in about 100% diastolic and 80% systolic values for the second interval after 8 weeks. These results could be reproduced without relevant differences for the respective single outcome in the four treatment groups. Regarding the primary study efficacy criterion the achieved lowering of blood pressure was highly statistically significant with p-values < 0.0001 in all 4 groups both for systolic and diastolic results. In addition, the long-term action over 48 h could be confirmed by the specific analysis according to Bonferroni-Holm showing that the p-values of all eight hypotheses were below the adjusted significance levels, i.e. in terms of the systolic and diastolic endpoints within the 4 treatment groups. Furthermore, statistically significant differences between the four treatment arms could not be detected regarding the long-lasting blood pressure lowering effect over As for tolerability the entire study provides no evidence on new or unknown pathologic drug reactions as well as on a frequent occurrence of specific adverse events or relevant laboratory changes. The objectives of the present study were completely met by confirming statistically and clinically the assumption of a clear, long-lasting, safe and metabolically neutral action of CC both for low and high dosages with or without HCT. The intended lowering of blood pressure is effective and well tolerable also repeatedly during the 48-h, therapy-free interval (missed dose trial) which corresponds to a frequent omission of the daily tablet dose and thus well reflects the daily practice in antihypertensive therapeutic regimens.


Grabbing Plk1 by the PBD.
A new centromeric protein termed PBIP1 was identified that recruits Plk1 to the kinetochores. In the November 3 issue of Molecular Cell, show that Plk1 phosphorylates PBIP1 on threonine 78, creating its own high-affinity docking site for the polo-box domain (PBD).


Electroantennogram responses of Nilaparvata lugens (Homoptera: Delphacidae) to plant volatile compounds.
Electroantennogram (EAG) recordings were made from the plaque organ receptors of the rice brown plant hopper, Nilaparvata lugens (Stål). The receptors of the distal plaque organ of both male and female hoppers responded to the air from above chopped rice plants, and those of females gave a larger response. Female hoppers, tested with 27 plant volatiles, gave dose-related responses to 16 of the compounds, including a range of green leaf volatiles. The aliphatic aldehydes hexanal and (E)-2-hexenal elicited a larger response than a range of green leaf alcohols. Of the remaining compounds, acetophenone, benzaldehyde, ethyl and methyl benzoate, and amyl and isoamyl acetate were among the most effective in eliciting responses. Receptor recovery times showed some variation between compounds. A comparison of the dose-related response of 16 compounds in paraffin oil and in pentane showed that considerably larger responses were recorded when the highly volatile solvent pentane was used.


Sacrospinous fixation: Review of relevant anatomy and surgical technique.
Apical support is an important component of pelvic floor reconstruction for pelvic organ prolapse. Sacrospinous ligament fixation is a recognized procedure for apical support. Complications from sacrospinous ligament fixation include pain (buttock and leg) and bleeding. There is some debate as to the optimal location for placement of the sacrospinous fixation sutures. This review summarizes the neuroanatomy of the coccygeus sacrospinous ligament as it pertains to the sacrospinous ligament fixation procedure. An appreciation of the neuroanatomy will lead to a better understanding of methods to reduce operative complications and improve suture placement. This paper also describes a technique for the sacrospinous fixation procedure to better assist clinicians in dissecting the connective tissue off the ligament. Removing or clearing the connective tissue off the ligament will allow critical landmarks to be easily palpated and hence a more accurate placement of sutures. This in turn may reduce the risk of perioperative complications.


High Thermal Conductivity of Wurtzite Boron Arsenide Predicted by Including Four-Phonon Scattering with Machine Learning Potential.
Materials with high thermal conductivity are of great importance to the thermal management of modern electronic devices. Recently, it was found that cubic boron arsenide (c-BAs) is a high thermal conductivity (κ) material with a value of ∼1300 W/(m·K) at room temperature (RT), where four-phonon scattering plays a crucial role in limiting the κ. In this work, with four-phonon scattering included, we find that the κ of wurtzite BAs (w-BAs) reaches as high as 1036 W/(m·K) along the a-b plane at RT, decreasing by 43% compared to the calculation without considering four-phonon scattering. The similar phonon transport properties between c-BAs and w-BAs can be understood in terms of similar projected density of states and scattering rates, which have the origin in crystal structural resemblance. To accelerate the calculation, the moment tensor potential derived from machine learning is adopted and proven to be a reliable and efficient method to obtain high-order interatomic force constants.


Biomimetic Patch with Wicking-Breathable and Multi-mechanism Adhesion for Bioelectrical Signal Monitoring.
Wearable bioelectrical monitoring devices can provide long-term human health information such as electrocardiogram and other physiological signals. It is a crucial part of the remote medical system. These can provide prediction for the diagnosis and treatment of cardiovascular disease and access to timely treatment. However, the patch comfort of the wearable monitoring devices in long-term contact with the skin have been a technical bottleneck of the hardware. In this study, the biomimetic patch with wicking-breathable and multi-mechanism adhesion performance to achieve adaptability and comfortability to human skin has been reported. The patch was designed based on a conical through-hole and hexagonal microgroove to directionally transport sweat from skin to air which gives the patch the breathable performance. The breathable and drainage capability of the biomimetic patch was experimentally verified by analyzing the conical through-hole and hexagonal microgroove with the structural mechanism of wicking. Multi-mechanism adhesion of the Ag/Ni microneedle array and PDMS-t adhesion material ensures the stability of patch signal acquisition. This study provides a new way for enhancing the breathability and adaptability of the patch to realize accurate bioelectrical signal monitoring under sweat conditions on human skin.


Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.
This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance.


An unusual case of lymphedema tarda.
Lymphedema is the result of the equilibrium between the load to be cleared and the transport capacity of the clearing system. Lymphedema may be classified as primary or secondary, based on the underlying etiology. Primary lymphedema is an unusual disorder characterized by inadequate lymphatic drainage. Lymphedema tarda is a rare form of primary lymphedema. The case of lymphedema tarda documented here was chronic, progressive, and resistant to medical therapy and recurred several times after previous operations. We performed two-staged operations and we recommend that the staged excisional procedures offers reliable long-term improvement and minimizes postoperative complications in chronic advanced lymphedema.


Warfarin and the vitamin K-dependent gamma-carboxylation system.
Insight into the molecular basis for genetic warfarin resistance has recently been accomplished by the identification of an 18-kDa protein of the endoplasmic reticulum that is targeted by the drug. When expressed in eukaryotic and insect cells, the protein reduces vitamin K1 2,3-epoxide in a warfarin-sensitive reaction. This finding strongly suggests that the protein is part of the vitamin K cycle, which is essential for the production of vitamin K-dependent proteins. Identification of the 18-kDa protein has aided the understanding of the vitamin K-dependent gamma-carboxylation system at the molecular level.


A survey of sleep habits and sleeping difficulties in an elderly Swedish population.
A random sample of 876 subjects aged 65-79 years were investigated by means of a questionnaire concerning sleep and related factors. Sleep problems were reported by 23.8% of females and 13.3% of males. Moderate or major complaints of maintaining sleep were reported by 43.5% of subjects, early morning awakening 33.4% and difficulties falling asleep 31.4%. Daytime sleepiness was more common among males, and a relationship between daytime sleepiness and perceived poor sleep was found. Daytime napping was common, but not related to poor sleep. The prevalence of regular sleeping pill users was 7.6% for females and 3.0% for males and a relationship between sleep problems, sleeping pill usage and psychiatric symptoms was established. Among the regular sleeping pill users 39.1% had possible depression (PD) and 63.0% had possible anxiety disorder (PA). Among respondents with sleep complaints 29.8% had PD and 48.7% had PA. Sleep problems were also related to impaired physical health. Various medical illnesses contributed to sleep complaints among males, and depression affected sleep the most among females.


Redox state switching of transition metals by deprotonation of the tridentate ligand 2,6-bis(imidazol-2-yl)pyridine.
The chemistry of the ligand 1, 2,6-bis(imidazol-2-yl)pyridine with manganese, cobalt, nickel and ruthenium has been investigated. The ligand binds as a meridional tridentate ligand as shown by the crystal structures of [Mn(1)2](CF3SO3)2 x Et2O and [Ru(1)2](PF6)2 x 2CH3CN x H2O. The coordinated ligand is deprotonated in mildly basic solution, and this leads to a drop in the metal M(III)/M(II) reduction potential for cobalt and ruthenium of roughly 1.3 V. The crystal structure of Na2(PPN)[Co(1 - 2H)2]2(OH) x MeOH x 2H2O confirms the deprotonation and shows sodium to bind to the deprotonated nitrogen atoms. No stabilisation of the M(III) oxidation state was observed for nickel and manganese.


Influence of age and immunization on development of gingivitis in rats.
To study the effect of age and antigenic priming on the development of gingivitis, 33 healthy rats were placed in contact with Streptococcus mutans, Actinomyces viscosus, Fusobacterium nucleatum, and Bacteroides gingivalis. On days 0, 3, 7, and 14 after inoculation, the gingival condition was judged clinically and histologically, and serum antibody titers against the bacteria were measured. The rats were divided into three groups: 1 month old, 3 months old, and 3 months old immunized. None of the young rats developed gingivitis during the experiment, whereas half of the adult and all of the adult immunized rats bled on probing on days 7 and 14. In general, antibody titers against the bacteria were low in young rats, moderate in adult rats, and high in adult immunized rats. These results indicate that adult rats react stronger to plaque antigens than young rats and that previous contact with the antigens increases the reaction.


Powdery Mildew Resistant Rootstocks that Impart Tolerance to Grafted Susceptible Watermelon Scion Seedlings.
Powdery mildew (PM) is a major foliar disease causing serious economic losses of cucurbit crops grown in the United States. The pathogen Podosphaera xanthii, which causes PM, is known to infect seedlings, stems, foliage, petioles, and fruit of cucurbit crops. In recent years, grafting watermelon on resistant rootstocks for managing soilborne diseases has been gaining popularity in the U.S.A. However, grafting for managing foliar diseases has not yet received adequate attention. Three greenhouse experiments were conducted during the summer months of 2012, 2013, and 2014 to determine if PM-resistant rootstocks could impart resistance to a susceptible watermelon scion. Susceptible watermelon scion 'Mickey Lee' seedlings were grafted onto 25 watermelon (Citrullus lanatus, C. amarus, C. mucosospermus) and four bottle gourd (Lagenaria siceraria) rootstocks. Grafted plants were inoculated with a 2 × 104 conidia ml-1 suspension of P. xanthii conidia and disease severity was rated 14 days after inoculation. Mickey Lee grafted on six PM-resistant watermelon rootstocks had significantly (P ≤ 0.05) lower PM severity on cotyledons, 2nd true leaf, and upper leaves (rating for 3rd to 7th or 8th true leaf) compared with Mickey Lee grafted on susceptible watermelon USVL677-PMS or bottle gourd USVL848-PMS rootstocks. However, some of the resistant watermelon rootstocks did not impart significant resistance to the scion. The resistant bottle gourd rootstocks USVL482-PMR and USVL351-PMR provided significantly greater levels of resistance, compared with many of the resistant watermelon rootstocks. Grafting watermelon on resistant rootstocks may help mitigate the effects of PM on susceptible scion seedlings.


Approaches to community nursing research partnerships: a case example.
Every community is unique and has special strengths and health-related needs, such that a community-based participatory research partnership cannot be formed and implemented in a predetermined, step-by-step manner. In this article, we describe how the Community Partnership Model (CPM), designed to allow flexible movement back and forth through all action phases, can be adapted to a variety of communities. Originally developed for nursing practice, the CPM has evolved into approaches for the collaborative initiation and maintenance of community partnerships. The model is informed by the recognition that cultural, social, economic, and knowledge backgrounds may vary greatly between nurse researchers and their community partners. The Familias En Acción violence prevention project exemplifies the use of the CPM in a transcultural partnership formation and implementation process. The collaborative approaches of the model guide community and research partners to interconnect and move flexibly through all partnership phases, thereby facilitating sustainability and community self-advocacy.


Decorporation of inhaled americium-241 dioxide and nitrate from hamsters using ZnDTPA and Puchel.
Accidental intakes of 241AmO2 and 241Am(NO3)3 can be treated with some success by inhalation of ZnDTPA . The main advantage of this method of treatment is that it can be self-administered very soon after an accidental intake, and it is effective for reducing the lung content of Am at doses about 10 times less than those usually used intravenously. Otherwise the efficacy of injected ZnDTPA is superior since in addition to removing 241Am from the lungs it can deplete appreciably the systemic deposit of the nuclide. There appears to be no advantage in using the lipophilic form of DTPA code-named Puchel , since following the inhalation or injection of the compound decorporation is not significantly increased relative to ZnDTPA .


A Computational Approach to Investigate the HDAC6 and HDAC10 Binding Propensity of Psidium guajava-derived Compounds as Potential Anticancer Agents.
Different parts of Psidium guajava are consumed as food and used for medicinal purposes around the world. Although studies have reported their antiproliferative effects via different biochemical mechanisms, their modulatory effects on epigenetic modification of DNA molecules via histone deacetylases (HDACs) are largely unknown. This study was carried out to investigate the histone deacetylase 6 (HDAC6) and histone deacetylase 10 (HDAC10) binding propensity of guava-derived compounds, using in silico methods, in other to identify compounds with HDAC inhibitory potentials. Fifty-nine guava-derived compounds and apicidin, a standard HDAC inhibitor, were docked with HDAC6 and HDAC10 using AutodockVina after modeling (SWISS-MODEL server) and validating (ERRAT and VERIFY-3D) the structure of HDAC10. Molecular interactions between the ligands and the HDACs were viewed with Discovery Studio Visualizer. Prediction of binding sites, surface structural pockets, active sites, area, shape and volume of every pocket and internal cavities of proteins was done using Computed Atlas of Surface Topography of proteins (CASTp) server, while absorption, distribution, metabolism, and excretion (ADME) study of notable compounds was done using Swiss online ADME web tool. 2α-hydroxyursolic acid, asiatic acid, betulinic acid, crategolic acid, guajadial A and B, guavacoumaric acid, guavanoic acid, ilelatifol D, isoneriucoumaric acid, jacoumaric acid, oleanolic acid, psiguadial A, B, and C demonstrated maximum interaction with the selected HDACs. ADME studies revealed that although isoneriucoumaric and jacoumaric acid ranked very high as HDAC inhibitors, they both violated the Lipinski's rule of 5. This study identified 13 drugable guava-derived compounds that can be enlisted for further studies as potential HDAC6 and HDAC10 inhibitors.


Searching for and use of conference abstracts in health technology assessments: policy and practice.
Current policy and practice regarding identification of and extent of use of data from conference abstracts in health technology assessment reviews (TARs) are examined. The methods used were (i) survey of TAR groups to identify general policy and experience related to use of abstract data, and (ii) audit of TARs commissioned by the National Institute for Health and Clinical Excellence (NICE) and published between January 2000 and October 2004. Five of seven TAR groups reported a general policy that included searching for and including studies available as conference abstracts and presentations. A total of sixty-three published HTA reports for NICE were identified. Of these reports, thirty-eight identified at least one randomized controlled trial available as an abstract/presentation. Twenty-six (68 percent) of these thirty-eight TARs included studies available as abstracts. There are variations in policy and practice across TAR groups regarding the searching for and inclusion of studies available as conference abstracts. There is a need for clarity and transparency for review teams regarding how abstract data are managed. If conference abstracts are to be included, reviewers need to allocate additional time for searching and managing data from these sources. Review teams should also be encouraged to state explicitly their search strategies for identifying conference abstracts, their methods for assessing these abstracts for inclusion and, where appropriate, how the data were used and their effect on the results.


Thirty-year stability after regeneration of a deep intrabony defect: a case report.
Report clinical improvements and 30-year stability of clinical outcomes of an intrabony defect treated with non-resorbable barriers and mucogingival surgery. A 18-year-old male presenting with a very severe intrabony defect at the upper right central incisor was treated with periodontal regeneration with non-resorbable barriers and a fibrin-fibronectin glue. The barriers were removed after 3 months. At 6 months, a free gingival graft (FGG) was positioned to improve mucogingival conditions. The patient was enrolled into a 6-month supportive periodontal care programme (SPC) for 30 years. Clinical attachment level (CAL) of 16 mm was associated with a 12 mm osseous defect and a pocket (PD) 14 mm deep. At 1 year, a CAL of 5 mm was associated with a PD of 2 mm. The 5 mm gingival recession measured at 6 months and treated with FGG was reduced to 3 mm. Measurements taken at 10, 20 and 30 years showed a consistent creeping of the gingival margin. At 30-year examination, CAL gain was 12 mm associated with a 2 mm PD and a minimal gingival recession. This case demonstrates that it is possible to treat a very severe infrabony pocket applying regeneration and mucogingival surgery and to maintain the clinical outcomes for 30 years.


[IMPACT OF ATORVASTATIN AND ROSUVASTATIN ON RESIDUAL ON-CLOPIDOGREL TREATMENT PLATELET REACTIVITY IN PATIENTS WITH ISCHEMIC HEART DISEASE AND TYPE 2 DIABETES MELLITUS AFTER ACUTE CORONARY SYNDROME].
In patients with ischemic heart disease and type 2 diabetes mellitus in 4-6 weeks after acute coronary syndrome (ACS) on stable dual antiplatelet therapy (DAPT) with aspirin and clopidogrel co-adminstrated with rosuvastatin residual platelet reactivity on adenosine diphosphate was higher than in patients receiving atorvastatin. However, the rate of high residual on-clopidogrel treatment platelet reactivity (RCPR) in rosuvastatin-treated patients exceeded the rate of high RCPR in atorvastatin-treated patients insignificantly. In 6 months after ACS residual platelet reactivity did not differ between the groups. After 12 months of DAPT platelet reactivity increased as compared to baseline values both in patients receiving rosuvastatin and in patients receiving atorvastatin without switching. In patients, randomly switching from one statin type to another at 6 month of treatment, platelet reactivity did not change significantly in comparison to baseline and the prevalence of high RCPR was lower than in patients receiving statins without switching. Thus, in patients with diabetes with ACS on DAPT with acetylsalicylic acid and clopidogrel statin treatment should be started with atorvastatin and in 6 months after ACS atorvastatin should be switched to rosuvastatin. This approach will provide lower RCPR within at least first 4-6 weeks after ACS and prevent RCPR increase during 12 months of DATT use in this patients group.


Guided tissue regeneration: an adjunct to endodontic surgery.
Membrane barriers used in conjunction with periodontal surgery have promoted regeneration of lost marginal attachment. Membrane barriers also may be indicated during surgical endodontics, in selected cases, where primary apical lesions are complicated by the loss of marginal attachment. The indications for using guided tissue regeneration in endodontic surgery are discussed and two cases are presented.


Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter.
Major histocompatibility complex (MHC) class I molecules present peptides derived from nuclear and cytosolic proteins to CD8+ T cells. These peptides are translocated into the lumen of the endoplasmic reticulum (ER) to associate with class I molecules. Two MHC-encoded putative transporter proteins, TAP1 and TAP2, are required for efficient assembly of class I molecules and presentation of endogenous peptides. Expression of TAP1 and TAP2 in a mutant cell line resulted in the delivery of an 11-amino acid oligomer model peptide to the ER. Peptide translocation depended on the sequence of the peptide, was adenosine triphosphate (ATP)-dependent, required ATP hydrolysis, and was inhibited in a concentration-dependent manner.


Irradiation-induced changes in secretion and composition of rat saliva.
The aim of this study was to monitor changes in the composition and the rate of secretion of rat whole, parotid and submandibular/sublingual saliva after local irradiation of the salivary gland region with a single dose of 10 Gy. Before and 1-30 days after irradiation, saliva samples were collected after stimulation with pilocarpine. Maximum changes in the latent period, the flow rate and the composition of parotid and submandibular/sublingual saliva were observed three days after a radiation dose of 10 Gy. Partial recovery was seen for the latent period, [Pi], [Ca2+] and concentration of amylase, whereas the flow rate and [Na+] remained low and [K+] remained high. The changes in whole saliva were similar to those observed for parotid and submandibular/sublingual saliva, although some variation was observed due to contamination with other contributions to oral fluid.


Testing for Quality and Safety Education for Nurses (QSEN): Reflections From Using QSEN as a Framework for RN Orientation.
The use of the Quality and Safety Education for Nurses (QSEN) competencies for nursing professional development is in its infancy. QSEN content was incorporated into nursing orientation and tested knowledge gain for three QSEN competencies. Results showed an increase in patient safety knowledge. A difference was noted in knowledge between ADN and BSN nurses for evidence-based practice and quality improvement. The results indicate a need for stronger interventions to build practicing nurses' QSEN competencies.


Flow cytometric analysis of porcine preadipocyte replication.
In the present study, a technique is described for measuring proliferation of primary porcine preadipocytes. Cultures of stromal-vascular (S-V) cells from dorsal subcutaneous adipose tissue were maintained under several growth conditions. Cells were isolated from cultures at various times and DNA was labeled with propidium iodide (PI) and analyzed by flow cytometry. Treatment of cultures with colchicine allowed identification of S-V cells in mitosis. The relative proportion of replicating cells was dependent on several factors, including serum concentration and cell density at the time of harvest. Using the AD-1 anti-preadipocyte/adipocyte monoclonal antibody, the preadipocyte subpopulation within the S-V cells was identified. Furthermore, by labeling cells with PI concomitant with AD-1, the proportion of replicating preadipocytes was quantified. It is now possible to identify and quantify replicating preadipocytes rapidly under various experimental conditions.


Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats.
The purpose of this study was to examine the hypoglycaemic effect of the lyophilised aqueous extract of the whole plant of Ajuga iva (L.) Schreber (Labiatae) in normal and streptozotocin-induced diabetic rats. Single and repeated oral administration of the extract of Ajuga iva L (AI) at a dose of 10 mg/kg produced a slight and significant decrease in plasma glucose levels in normal rats 6 h after administration and after 3 weeks of treatment. AI reduced plasma glucose levels of streptozotocin diabetic rats from 337+/-9.3 to 102.2+/-17.7 mg/dl after 6 h of oral administration (P<0.001). Repeated oral administration of AI to streptozotocin diabetic rats significantly decreased the plasma glucose levels after 1 week of treatment (112+/-14.4 mg/dl at 1 week vs 337+/-9.3 mg/dl at the baseline values, (P<0.001). It continuously decreased thereafter and showed a rapid normalisation after 1 week of AI treatment. It is concluded that these results demonstrated that the water extract of the whole plant of AI possess a strong hypoglycaemic effect in diabetic rats, and support therefore, its traditional use in diabetes mellitus control.


Secondary cell wall deposition in developing secondary xylem of poplar.
Although poplar is widely used for genomic and biotechnological manipulations of wood, the cellular basis of wood development in poplar has not been accurately documented at an ultrastructural level. Developing secondary xylem cells from hybrid poplar (Populus deltoides x P. trichocarpa), which were actively making secondary cell walls, were preserved with high pressure freezing/freeze substitution for light and electron microscopy. The distribution of xylans and mannans in the different cell types of developing secondary xylem were detected with immunofluorescence and immuno-gold labeling. While xylans, detected with the monoclonal antibody LM10, had a general distribution across the secondary xylem, mannans were enriched in the S2 secondary cell wall layer of fibers. To observe the cellular structures associated with secondary wall production, cryofixed fibers were examined with transmission electron microscopy during differentiation. There were abundant cortical microtubules and endomembrane activity in cells during the intense phase of secondary cell wall synthesis. Microtubule-associated small membrane compartments were commonly observed, as well as Golgi and secretory vesicles fusing with the plasma membrane.


Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients.
Neutral endopeptidase (CD10), an ectopeptidase bound to the cell surface, is thought to be a potential prognostic marker for prostate cancer. Prostate cancer patients (N = 3,261) treated by radical prostatectomy at a single institution were evaluated by using tissue microarray. Follow-up data were available for 2,385 patients. The cellular domain (membranous, membranous-cytoplasmatic, and cytoplasmatic only) of CD10 expression was analyzed immunohistochemically and correlated with various clinical and histopathologic features of the tumors. CD10 expression was detected in 62.2% of cancer samples and occurred preferentially in higher Gleason pattern (P < 0.0001). CD10 expression positively correlated with adverse tumor features such as elevated preoperative prostate-specific antigen (PSA), higher Gleason score, and advanced stage (P < 0.0001 each). Survival analyses showed that PSA recurrence was significantly associated with the staining pattern of CD10 expression. Outcome significantly declined from negative over membranous, membranous-cytoplasmatic, to exclusively cytoplasmatic CD10 expression (P < 0.0001). In multivariate analysis, CD10 expression was an independent predictor for PSA failure (P = 0.0343). CD10 expression is an unfavorable independent risk factor in prostate cancer. The subcellular location of CD10 protein is associated with specific clinical courses, suggesting an effect on different important biological properties of prostate cancer cells. The frequent expression of CD10 in prostate cancer and the strong association of CD10 with unfavorable tumor features may qualify this biomarker for targeted therapies.


Uptake, Distribution, and Transformation of CuO NPs in a Floating Plant Eichhornia crassipes and Related Stomatal Responses.
Engineered nanoparticles (NPs) are being released into aquatic environments with their increasing applications. In this work, we investigated the interaction of CuO NPs with a floating plant, water hyacinth (Eichhornia crassipes). CuO NPs (50 mg/L) showed significant growth inhibition on both roots and shoots of E. crassipes after 8-day exposure, much higher than that of the bulk CuO particles (50 mg/L) and their corresponding dissolved Cu2+ ions (0.30 mg/L). Scanning electron and light microscopic observations showed that the root caps and meristematic zone of E. Crassipes were severely damaged after CuO NP exposure, with disordered cell arrangement and a destroyed elongation zone of root tips. It is confirmed that CuO NPs could be translocated to shoot from both roots and submerged leaves. As detected by X-ray absorption near-edge spectroscopy analysis (XANES), CuO NPs were observed in roots, submerged leaves, and emerged leaves. Cu2S and other Cu species were also detected in these tissues, providing solid evidence of the transformation of CuO NPs. In addition, stomatal closure was observed during CuO NPs-leaf contact, which was induced by the production of H2O2 and increased Ca level in leaf guard cells. These findings are helpful for better understanding the fate of NPs in aquatic plants and related biological responses.


VviWRKY40, a WRKY Transcription Factor, Regulates Glycosylated Monoterpenoid Production by VviGT14 in Grape Berry.
Glycosylated volatile precursors are important, particularly in wine grape berries, as they contribute to the final aroma in wines by releasing volatile aglycones during yeast fermentation and wine storage. Previous study demonstrated that VviGT14 was functioned as a critical monoterpene glucosyltransferase in grape berry, while the transcriptional regulation mechanism of VviGT14 was still unknown. Here we identified VviWRKY40 as a binding factor of VviGT14 promoter by both DNA pull-down and yeast one-hybrid screening, followed by a series of in vitro verification. VviWRKY40 expression pattern negatively correlated with that of VviGT14 in grape berries. And the suppressor role of VviWRKY40 was further confirmed by using the dual luciferase assay with Arabidopsis protoplast and grape cell suspension system. Furthermore, the grape suspension cell ABA treatment study showed that ABA downregulated VviWRKY40 transcript level but promoted that of VviGT14, indicating that VviWRKY40 was at the downstream of ABA signal transduction network to regulate monoterpenoid glycosylation. These data extend our knowledge of transcriptional regulation of VviGT14, and provide new targets for grape breeding to alter monoterpenoid composition.


Macrodystrophia lipomatosa: a case report.
Macrodystrophia lipomatosa is a rare congenital form of localized gigantism, characterized by an increase in all mesenchymal elements, particularly fibroadipose tissue. The areas of predilection are segments supplied by the median or plantar nerves. We report such a rare case in a thirty four year old male patient, who presented with a swelling of the right upper limb and a marked increase in the size of the right thumb, index finger and radial half of the right hand, present since birth, with progressive increase to the present size. Amputation of the right thumb and debulking of the palm was done. The specimen measured 26 x 18 x 12 cms. and the thumb alone measured 13 x 7 x 7 cm. histology revealed hypertrophy of adipose tissue in the subcutaneous compartment and infiltration into the nerve sheaths and muscles.


Eukaryotic expression vectors that replicate to low copy number in bacteria: transient expression of the Menkes protein.
A set of low copy number plasmid vectors for mammalian gene expression has been constructed. These vectors are derived from the previously described bacterial low copy number expression vectors, pWSK29 and pWKS30, which are present at six to eight copies per cell. The new plasmids also have the following useful properties: (1) they contain antibiotic resistance markers for the selection of stable mammalian cell lines; (2) they have either constitutive or inducible promoters; (3) a chimeric intron, for enhancing gene expression, is present; (4) they contain unique cloning sites; (5) they have an SV40 polyadenylation signal, and a subset of the vectors have an SV40 origin of replication for episomal replication and transient gene expression. A cDNA encoding the Menkes disease protein was cloned into two of these vectors, and transient expression studies in COS-7 cells showed that both constitutive and inducible expression was possible. This set of expression vectors will provide a useful tool for the manipulation, in Escherichia coli, of mammalian genes or cDNAs that are unstable in the high copy number vectors that are currently available.


Chinese herbs nephropathy: a clue to Balkan endemic nephropathy?
Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including Chinese herbs. We examined four nephroureterectomies performed in three patients prior to or at the time of transplantation to determine the nature and topography of the kidney and urinary tract lesions in Chinese herbs nephropathy (CHN). Extensive, hypocellular, interstitial sclerosis, tubular atrophy and global sclerosis of glomeruli decreasing from the outer to the inner cortex, including the columns of Bertin, were observed in the four kidney specimens, together with severe fibromucoid to fibrous intimal thickening, mainly of interlobular arteries, normal or collapsed residual glomeruli, and mild to moderate atypia and atypical hyperplasia of the urothelium. In addition, bilateral pelvi-ureteric sclerosis was observed in one case. With the exception of the latter, these lesions are very similar to those described in Balkan endemic nephropathy (BEN). The clinical presentation of the patients was also similar to that observed in BEN: normal blood pressure, aseptic leukocyturia, low grade low molecular weight proteinuria, early and severe anemia. In conclusion, on morphological and clinical grounds, CHN appears similar to BEN. A common etiologic agent, aristolochic acid, is suspected. The known carcinogenic potential of this compound, taken together with our finding of multiple foci of cellular atypia of the urothelium suggest that CHN patients should undergo a regular follow-up for urothelial malignancy.


Donor site evaluation: anterior iliac crest following secondary alveolar bone grafting.
The use of autogenous bone graft for Secondary alveolar bone grafting is well established in the treatment of cleft lip and palate patients. To evaluate post-operative morbidity of anterior iliac crest graft after secondary alveolar bone grafting in cleft patients. Forty patients during the period from July 2008 to March 2013, who underwent secondary alveolar bone grafting by harvesting graft from anterior iliac crest in Mamata Dental Hospital, Khammam, Andhra Pradesh, India are included in the present study. Unilateral and bilateral cleft patients who had undergone secondary alveolar bone grafting (SABG) with anterior iliac crest as their donor site have been selected and post- operative complications from the surgery were evaluated with the help of a questionnaire which included pain, gait disturbances, numbness and scar problems (infection, irritation). Patients who were operated gave maximum score for pain as 8 on visual analogue scale. No pain was observed in any of the cases after 8 days, gait disturbances were seen in all patients (limping) for 2-6 days, there was no post-operative numbness with all the patients returning to their routine in 6- 15 days and 90% of the patients gave a satisfied response towards scar. From the results in our study the morbidity after harvesting bone from iliac crest was found to be moderate to low, which had minimal complications and were well tolerated and greater acceptance from the patient.


FEEDBACK trial - A randomised control trial to investigate the effect of personalised feedback and financial incentives on reducing the incidence of road crashes.
Road crashes continue to pose a significant threat to global health. Young drivers aged between 18 and 25 are over-represented in road injury and fatality statistics, especially the first six months after obtaining their license. This study is the first multi-centre two-arm parallel-group individually randomised controlled trial (the FEEDBACK Trial) that will examine whether the delivery of personalised driver feedback plus financial incentives is superior to no feedback and no financial incentives in reducing motor vehicle crashes among young drivers (18 to 20 years) during the first year of provisional licensing. A total of 3,610 young drivers on their provisional licence (P1, the first-year provisional licensing) will participate in the trial over 28 weeks, including a 4-week baseline, 20-week intervention and 4-week post-intervention period. The primary outcome of the study will be police-reported crashes over the 20-week intervention period and the 4-week post-intervention period. Secondary outcomes include driving behaviours such as speeding and harsh braking that contribute to road crashes, which will be attained weekly from mobile telematics delivered to a smartphone app. Assuming a positive finding associated with personalised driver feedback and financial incentives in reducing road crashes among young drivers, the study will provide important evidence to support policymakers in introducing the intervention(s) as a key strategy to mitigate the risks associated with the burden of road injury among this vulnerable population. Registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12623000387628p on April 17, 2023.


Deep learning enhanced achromatic imaging with a singlet flat lens.
Correction of chromatic aberration is an important issue in color imaging and display. However, realizing broadband achromatic imaging by a singlet lens with high comprehensive performance still remains challenging, though many achromatic flat lenses have been reported recently. Here, we propose a deep-learning-enhanced singlet planar imaging system, implemented by a 3 mm-diameter achromatic flat lens, to achieve relatively high-quality achromatic imaging in the visible. By utilizing a multi-scale convolutional neural network (CNN) imposed to an achromatic multi-level diffractive lens (AMDL), the white light imaging qualities are significantly improved in both indoor and outdoor scenarios. Our experiments are fulfilled via a large paired imaging dataset with respect to a 3 mm-diameter AMDL, which guaranteed with achromatism in a broad wavelength range (400-1100 nm) but a relative low efficiency (∼45%). After our CNN enhancement, the imaging qualities are improved by ∼2 dB, showing competitive achromatic and high-quality imaging with a singlet lens for practical applications.


Metal-binding and nuclease activity of an antimicrobial peptide analogue of the salivary histatin 5.
The salivary antimicrobial peptide histatin 5 is characterized by its cationic nature, structural flexibility, and the presence of two metal-binding sites (the ATCUN motif and a Zn-binding motif). These properties make this peptide a good model for the design of new drugs of low molecular weight. In this work, we have synthesized and studied a new peptide, an analogue of the histatin 5 named ATCUN-C16, which contains both metal-binding centers. The results show that our 20-residue-derived peptide preserves anticandidal activity and exhibits a higher propensity to assume a stable conformation in a hydrophobic environment than do histatin 5 and the C16 peptide that contains the 16 residues of the C-terminal part of histatin 5, although overall our peptide remains a flexible molecule. ACTUN-C16 was found to bind DNA in a gel retardation assay and to have a nuclease activity in the presence of copper and zinc ions and ascorbate. Its nuclease activity can be attributed to the synergistic action of oxidative and hydrolytic activities due to the Cu-ATCUN complex and to the zinc ion coordination, respectively. The results show a new property of this family of salivary peptides and suggest a novel use of this peptide as a small nuclease and biotechnological tool.


Traumatic brain injury and Alzheimer's: deficit profile similarities and the impact of normal ageing.
Research has suggested that sustaining a traumatic brain injury (TBI) may increase one's risk of developing Dementia of the Alzheimer's Type (DAT) later in life. Several neuropathological models have been proposed to explain the association between TBI and DAT and studies using a neuropsychological deficit profile methodology suggest that the pattern and extent of cognitive decline associated with these conditions are similar. This paper presents a new conceptual model, derived from deficit profile methodology, regarding the relationship between TBI and DAT. This model proposes that, for some individuals, TBI may not lead to true DAT neuropathology, but rather produces a profile of neuropsychological deficits similar to DAT, which increasingly mimics the symptoms of true DAT as the TBI survivor ages. Understanding how TBI may contribute to the development of DAT has important social and medical implications, influencing the direction of prevention efforts and contributing to one's understanding of DAT.


Mannose-Binding Lectin (MBL) gene polymorphisms in susceptibility to pulmonary tuberculosis among the Lur population of Lorestan Province of Iran.
Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL polymorphisms and TB has been studied in various populations, the results are controversial. The aim of this study was to investigate mannose-binding lectin (MBL) gene polymorphisms with susceptibility to pulmonary tuberculosis (PTB) in a Lur population of Iran. In this case-control study, four functional MBL gene polymorphisms (HL, XY, PQ and AB) were genotyped by using PCR Single Strand Conformation Polymorphism (SSCP) technique in a Lur population living in Lorestan Province, consisting of 100 patients with pulmonary tuberculosis (PTB) age and sex matched 100 healthy controls (HCs). Association analyses were performed with the SPSS 21 statistical software. We found that MBL (HH) genotype polymorphism significantly was associated with increased susceptibility to TB (35% in patients vs. 22% in controls, P = 0.0417, OR = 1.909, %95 CI = 1.020-3.573). Additionally, H allele showed a significant association with increased risk of TB (56.5% in patients vs. 46% in controls, P = 0.0357, OR = 1.525, %95 CI = 1.028-2.262). Also, the distribution of L allele in patients was significantly lower frequency in TB patients compared to controls (43.5% vs. 54%, P = 0.0357, OR = 0.656, %95 CI = 0.442-0.973). However, the allelic and genotypic frequencies of AB, XY and PQ polymorphisms were not significantly different between the patients and the controls. We couldn't detect any significant differences between haplotypes among TB patients and healthy controls. Our findings demonstrated that HH genotype and H allele may increase the susceptibility to pulmonary TB in the Lur population of Iran, although L allele may decrease the susceptibility to pulmonary TB in this population. We suggest that it is necessary to further more studies with larger sample size and other ethnic population.


Unusual Cause of Acute Scrotal Pain-Inflammatory Noncommunicating Hydrocele: A Pediatric Case Report.
The etiology of scrotal pain is clinically classified in terms of the necessity for emergency surgery. Lately, color Doppler ultrasonography has reduced unnecessary surgeries, but there are still some cases that require immediate exploration because of an uncertain diagnosis. Here, we describe the case of a 14-month-old boy, who could not deliver his complaint accurately, presenting with a grumpy mood and a red swollen scrotum. Emergency surgery revealed that the cause was intense inflammation of the hydrocele wall, which typically does not cause acute scrotum. We also reviewed rare etiologies of scrotal pain for general physicians to develop the differential diagnosis.


[Home care situations : discontinuity of trajectories].
Introduction :The aging of the population in Western Europe led to a substantial increase of home-based care services. These services are quite simple in nature, but very complex to provide in the community. Little is known about how they are actually provided.Aim :By the mean of trajectory and arc of work analysis, the aim of this qualitative sociological study is to understand how support and care activities are ran in their local context.Method :Eight home care situations where observed during a period of three months, in three different home-based centers of one French speaking canton of Switzerland. Data collection included semi-structured and ethnographic interviews, service documents, key reference documents and observation of work practices in natural settings.Results :Data analysis showed that the standardization of evaluation practices - and a common frame of reference oriented by administrative principles - limited the possibility to problematize situations as a whole, from a caring point of view. As a consequence, services are mainly delivered in a fractionated way - and work organization is presently driven by compliance concerns.Conclusion :The ongoing standardization of care processes is a challenge to individualized and community-based care.


Retention Strategies in Working With Justice-Involved Women.
Research-based findings with vulnerable populations are strengthened by strong retention rates at the time of postintervention data collection. Women in the criminal justice system face a variety of gender-specific challenges including histories of childhood and adult sexual and physical abuse, substance abuse, untreated mental health problems, and chronic housing insecurity that can hinder follow-up of a research sample. The authors highlight a variety of retention strategies that they successfully used in their work with women following incarceration in local county jails.


Probenecid, an organic anion transporter 1 and 3 inhibitor, increases plasma and brain exposure of N-acetylcysteine.
1. N-acetylcysteine (NAC) is being investigated as an antioxidant for several conditions including traumatic brain injury, but the mechanism by which it crosses membrane barriers is unknown. We have attempted to understand how the transporter inhibitor, probenecid, affects NAC pharmacokinetics and to evaluate the interaction of NAC with transporters. 2. Juvenile Sprague-Dawley rats were administered NAC alone or in combination with probenecid intraperitoneally. Plasma and brain samples were collected serially and NAC concentrations were measured. Transporter studies were conducted with human embryonic kidney-293 cells that overexpress organic anion transporter (OAT)1 or OAT3 and with human multi-drug resistance-associated protein (MRP)1 or MRP4 membrane vesicles. 3. NAC area under the curve was increased in plasma (1.65-fold) and brain (2.41-fold) by probenecid. The apparent plasma clearance was decreased by 65%. Time- and concentration-dependent NAC uptake that was inhibitable by probenecid was observed with OAT1 and OAT3. No uptake of NAC was observed with MRP1 or MRP4. 4. Our results indicate for the first time that NAC is substrate for OAT1 and OAT3 and that probenecid increases NAC plasma and brain exposure in vivo. These data provide insight regarding how NAC crosses biological barriers and suggest a promising therapeutic strategy to increase NAC exposure.


The importance on the use of active methods when teaching human morphophysiology.
Traditional didactic methods have not been successful in promoting independent and reflective students. Thus new teaching techniques are essential to optimize the way students learn. This study aimed to evaluate the perception of students, from the Faculty of Ceilandia, University of Brasília (FCE/UnB), about the active method "inverted class," which has as its primary characteristic to stimulate the student to study and research the contents before the theoretical classes or explanation of the teacher. To this end, 64 students of the summer course participated in the Flipped Classroom and later evaluated the discipline method. Initially, they received a script with clinical questions about the class's content, which should be discussed and answered about the basic, clinical, and practical application concepts. To evaluate the didactic method applied, on the last day of class, the summer class students were invited to answer a survey about satisfaction when learning the contents. For 98% of the students, the teaching method used was approved. It is also emphasized that this class had 48 repeating students, unmotivated with the course because, for many, they declared themselves unable to be approved. Given the success of the method, we decided to apply it throughout 2018, so the method was applied to over 180 students of FCE/UnB health courses. In short, it is considered that the results presented here to support other studies that highlight the need for changes in traditional teaching methods, which is a didactic option in undergraduate courses.


Malingering of memory impairment on the Colorado Priming Test.
We hypothesized that simulated malingerers would show a weaker priming effect and a longer response latency than control patients and patients with a brain injury on a priming test. Participants were compared on their performance on the Colorado Priming Test to replicate and extend the original validation study. Of 33 participants, 16 were people with a brain injury and 17 were non-head injured control patients who were also instructed to feign cognitive impairment (simulators N = 17). Up to 88 per cent of simulating malingerers and 75 per cent of head-injured participants were correctly classified. The Colorado Priming Test may be useful in identifying patients feigning memory impairment.


Histological evaluation of bone response to pediatric endodontic pastes: an experimental study in guinea pig.
This study aimed to evaluate by the intra-osseous implant technique the most commonly used materials for pulp therapy in pediatric dentistry: calcium hydroxide (CH), Guedes Pinto paste and CTZ paste, according to FDI (1980) and ANSI/ADA (1982) recommendations. Thirty guinea pigs, 10 for each material, divided into experimental periods of 4 and 12 weeks received one implant on each side of the lower jaw symphysis. The external lateral tube wall served as control for the technique. At the end of the observation periods, the animals were euthanized and specimens were prepared for routine histological examination. It was observed that CH and CTZ paste induced severe inflammation, a large amount of necrotic tissue, lymphocytes, foreign body cells and bone resorption, while Guedes Pinto Paste induced little or no inflammation in the 4-week observation period. After 12 weeks, the reactions to CH and Guedes Pinto paste were also absent/mild, presenting a general pattern of replacement by recently formed bone tissue while a moderate to severe inflammatory response was observed with CTZ paste. Guedes Pinto paste presented acceptable biocompatibility levels in both analyzed periods; CH only showed acceptable biocompatibility in the 12-week period while CTZ paste showed no biocompatibility in both periods. Among the tested materials, only Guedes Pinto paste presented an acceptable biocompatibility.


Data-independent acquisition-based quantitative proteomic analysis reveals differences in host immune response of peripheral blood mononuclear cells to sepsis.
This study was aimed to uncover proteins that are differentially expressed in sepsis. Data-independent acquisition (DIA) was used for analysis to identify differentially expressed proteins in peripheral blood mononuclear cells (PBMCs) of patients. A total of 24 non-septic intensive care unit (ICU) patients, 11 septic shock patients and 27 patients diagnosed with sepsis were recruited for the mass spectrometry (MS) discovery. PBMCs were isolated from routine blood samples and digested into peptides. A DIA workflow was developed using a quadrupole-Orbitrap liquid chromatography LC-MS system, and mass spectra peaks were extracted by Skyline software. Orthogonal partial least-squares discriminant analysis (OPLS-DA) and partial least-squares discriminant analysis (PLS-DA) were applied to distinguish the patient groups at the level of fragment ion and peptide. Differentially expressed proteins in the patient groups were verified by enzyme-linked immunosorbent assay (ELISA). Receiver-operating characteristic (ROC) curves were used to evaluate the protein expression. A total of 1062 fragment ions and 122 proteins were identified in the MS-DIA analysis conducted by Skyline software. Using gene ontology clustering analysis, we discovered that 51 of the 122 identified proteins were associated with biological processes, including carbon metabolism, biosynthesis of antibiotics, platelet activation, bacterial invasion of epithelial cells and complement, and coagulation cascades. Among them, five proteins (high-mobility group box1 [HMGB1], matrix metalloproteinase 8 [MMP8], neutrophil gelatinase-associated lipocalin [NGAL], lactotransferrin [LTF] and grancalcin [GCA]) were identified by ELISA as closely related to the development of sepsis. The ROC curves displayed good sensitivity and specificity.