Mesenteric artery contractile properties during dietary calcium manipulation in spontaneously hypertensive and Wistar Kyoto normotensive rats.
The hypothesis that elevated Ca2+ intake lowers blood pressure in the spontaneously hypertensive rat (SHR) by altering intrinsic contractile properties of vascular smooth muscle was tested. The effect of 0.5, 1, and 2% Ca2+ in the diet on systolic blood pressure, serum-ionized Ca2+, and contractile properties of mesenteric arteries isolated from SHR and normotensive Wistar-Kyoto (WKY) rats maintained on diets for 6 and 12 weeks was examined. Blood pressure was significantly elevated in SHR on 0.5% Ca2+ diets after both 6 and 12 weeks, as well as in WKY receiving 1% Ca2+. After six weeks on the diets for the SHR and 6 and 12 weeks for the WKY, serum-ionized Ca2+ was a function of the amount of Ca2+ in the diet. When contractile force generation in response tp KCl or norepinephrine was examined, small diet-related differences were detected, but no consistent linear effect associated with the level of Ca2+ in the diet was observed in either strain. When the sensitivity of the vessels to KCl and norepinephrine was examined, no effects of oral Ca2+ intake were detected. The results indicate that oral Ca2+ loading has modest effects on blood pressure at both 12 and 18 weeks of age in the SHR and WKY and in the younger rat, where Ca2+ intake modulates serum ionized Ca2+ levels. At no age does modification of Ca2+ intake have a consistent effect on mesenteric artery sensitivity or force-generating ability in response to KCl or norepinephrine. These findings do not support the hypothesis that oral Ca2+ loading lowers blood pressure in the rat by altering intrinsic contractile properties of vascular smooth muscle.


Meiotic condensin is required for proper chromosome compaction, SC assembly, and resolution of recombination-dependent chromosome linkages.
Condensin is an evolutionarily conserved protein complex that helps mediate chromosome condensation and segregation in mitotic cells. Here, we show that condensin has two activities that contribute to meiotic chromosome condensation in Saccharomyces cerevisiae. One activity, common to mitosis, helps mediate axial length compaction. A second activity promotes chromosome individualization with the help of Red1 and Hop1, two meiotic specific components of axial elements. Like Red1 and Hop1, condensin is also required for efficient homologue pairing and proper processing of double strand breaks. Consistent with these functional links condensin is necessary for proper chromosomal localization of Red1 and Hop1 and the subsequent assembly of the synaptonemal complex. Finally, condensin has a Red1/Hop1-independent role in the resolution of recombination-dependent linkages between homologues in meiosis I. The existence of distinct meiotic activities of condensin (axial compaction, individualization, and resolution of recombination-dependent links) provides an important framework to understand condensin's role in both meiotic and mitotic chromosome structure and function.


A novel LacZ reporter mouse reveals complex regulation of the progesterone receptor promoter during mammary gland development.
To further our understanding of progesterone (P) as an endocrine mammogen, a PR(lacz) knockin mouse was generated in which the endogenous progesterone receptor (PR) promoter directly regulated lacZ reporter expression. The PR(lacz) mouse revealed PR promoter activity was restricted to the epithelial compartment during the prenatal and postnatal stages of mammary gland development. At puberty, PR promoter activity was unexpectedly robust and restricted to the body cells within the terminal end buds and to the luminal epithelial cells in the subtending ducts. In the adult, the preferential localization of PR(lacz) positive cells to the distal regions of ductal side branches provided a cellular context to the recognized mandatory role of P in ductal side-branching, and segregation of these cells from cells that undergo proliferation supported an intraepithelial paracrine mode of action for P in branching morphogenesis. Toward the end of pregnancy, the PR(lacz) mouse disclosed a progressive attenuation in PR promoter activity, supporting the postulate that the preparturient removal of the proliferative signal of P is a prerequisite for the emergence of a functional lactating mammary gland. The data suggest that PR expression before pregnancy is to ensure the specification and spatial organization of ductal and alveolar progenitor cell lineages, whereas abrogation of PR expression before lactation is required to enable terminal differentiation of the mammary gland.


Curative effect of radiotherapy at various doses on subcutaneous alveolar echinococcosis in rats.
Alveolar echinococcosis (AE) is a disease in human and animals, and the cure rate is unsatisfactory. This study aimed to investigate the curative efficacy of different doses of locally applied radiotherapy on alveolar echinococcosis in rats. Rats infected with Echinococcus multilocularis were randomly divided into 4 groups of 15 rats each: low-, middle-, and high-irradiation groups and a control group. Rats in the control group underwent no treatment, while rats in the irradiation groups received 6-MeV radiotherapy at 20 Gy/8 f, 40 Gy/8 f, and 60 Gy/8 f respectively, once every 3 days for a total of 8 times. One month after radiotherapy, wet weight and AE vesicle inhibitory rate were detected in rats of each group. Histopathologic and ultrastructural observations of tissues with AE lesions were performed. In the treatment groups, an obvious inhibitory effect was found in AE rats; the inhibitory rates were 50%, 72%, and 82%, respectively. There were also statistical differences in pathological changes and average wet weight of the lesions compared with the control group (P < 0.05). In the treatment groups, injuries of various degrees were found in the ultrastructure of the laminated and germinal layers in the capsular wall of AE, and injury was most severe in the high-dose group. Radiotherapy has a dose-dependent inhibitory effect on the growth of AE.


Metal complexes of chiral pentaazacrowns as conformational templates for beta-turn recognition.
Examples of reverse turns as recognition motifs in biological systems can be found in high-resolution crystal structures of antibody-peptide complexes. Development of peptidomimetics is often based on replacing the amide backbone of peptides by sugar rings, steroids, benzodiazepines, or other hetero- and carbocycles. In this approach, the chemical scaffold of the peptide backbone can be replaced while retaining activity as long as the pharmacophoric groups of the peptide side chains stay in relatively the same place; in other words, similar functional groups must overlap in space for interaction with critical receptor sites. This study evaluates the potential of metal complexes of chiral pentaazacrowns (PAC) derived by reduction of cyclic pentapeptides as beta-turn mimetics. Due to the limited flexibility of the pendant chiral side groups in these metal complexes, one can potentially elicit information about the receptor-bound conformation from their binding affinities. 11 PAC crystal structures with different substitution patterns complexed with 3 different metals (Mn, Fe, Cd) as a prototypical database of potential side-chain orientations. Complexation with different metals induces subtle differences in the conformations of a particular azacrown scaffold. The lack of parameterization of transition metals for force field calculations precludes a thorough theoretical study. Thus, this study utilizes a simple geometrical comparison between the experimental data for crystalline PAC complexes and the side-chain orientations seen in classic beta-turns. The FOUNDATION program was used to overlap the Calpha-Cbeta vectors of the corresponding ideal beta-turn side-chains to all possible leaving groups of the PAC complexes. When comparing the relative orientations of the chiral side chains, a strong overlap of the bonds (between about 0.1 A to about 0.5 A RMS for 3 residues and up to about 1 A RMS for 4 residues) was observed for many of the molecules. Such metal complexes may lack complete peptidomimetic activity due to the lack of spatial overlap of all four side-chain residues, however, if only three peptide side chains are needed for receptor recognition and/or binding, the metal complexes should show biological activity.


[Hormone content of the blood in neurotic patients].
Radioimmunoassay was applied to study the hormones (corticotropin, cortisol, T3, T4, testosterone, prolactin, follicle-stimulating and luteinizing hormones) in 52 male neurotic patients and 120 healthy donors in Arkhangelsk city, as compared to latitudinal mean values. In patients, prolactin, cortisol, thyroid hormones and gonadotropins were increased by 82.7%, 48.7%, 41%, 52.6%, respectively. Patients also had lower production of ACTH, higher blood contents of T3, prolactin and testosterone. Unidirectional shifts were detected in hormonal systems of neurotic patients, with respect to the time of the disease onset and the duration of last exacerbation: ACTH secretion increased with reduced response of adrenal cortisol production, compensatory increase in thyroid functions, redistribution of gonadotropic fractions increasing the FSH/LH ratio, decrease in testosterone production. At the initial stages prolactin secretion increased to reach later its plateau.


Mdm2 is required for HDAC3 monoubiquitination and stability.
HDAC3, one of the class I histone deacetylase modulates epigenetic landscape through histone modification. HDAC3 also interacts with non-histone proteins including p53 for deacetylation. Moreover, HDAC3 serves as a transcriptional repressor, interacting with NCor1/SMRT complex. Although HDAC3 plays a critical role for cellular homeostasis, regulatory mechanism of HDAC3 have been poorly understood. Here we report a novel regulatory mechanism of HDAC3 about its monoubiquitination and stabilization by Mdm2. HDAC3 levels were increased by ectopic expression of Mdm2 and decreased by Mdm2 ablation in various cell lines. We found that Mdm2 directly interacts with HDAC3 and induces HDAC3 protein levels without alteration of mRNA levels. Ectopic expression of wild type but not RING mutant of Mdm2 increased HDAC3 monoubiquitination. In addition, MdmX is beneficial for mdm2-mediated HDAC3 regulation. Ablation of Mdm2 and Mdm2/MdmX decreased cell migration along with the decrease of HDAC3 levels. These data provide an evidence that Mdm2 positively regulates HDAC3 monoubiquitination and stability.


CpG oligodeoxynucleotide and double-stranded RNA synergize to enhance nitric oxide production and mRNA expression of inducible nitric oxide synthase, pro-inflammatory cytokines and chemokines in chicken monocytes.
Toll-like receptors (TLRs) recognize microbial components and initiate the innate immune responses that control microbial infections. The interaction between ligands of TLR3 and TLR9, poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) on the inflammatory immune responses, including the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS), pro-inflammatory cytokines interleukin (IL)-1β and IL-6, and chemokines IL-8 and macrophage inflammatory protein (MIP)-1β, were investigated in chicken monocytes. The NO production was significantly higher when stimulated with a combination of CpG-ODN and poly I:C than with either CpG-ODN or poly I:C alone. Similarly, a significant synergistic effect by CpG-ODN and poly I:C was observed in the up-regulation of iNOS and IL-8 mRNA after 2 h and persisted up to 24 h. Although the combinatory treatment of CpG-ODN and poly I:C enhanced the expression of IL-1β, IL-6, and MIP-1β(3 after 2 h stimulation, the synergism in the up-regulation of IL-1β and IL-6 mRNA was observed after 8-h and 24-h stimulation, respectively, whereas there was no synergistic effect on MIP-1β. Our results demonstrate that CpG-ODN synergizes with poly I:C to induce pro-inflammatory immune response in chicken monocytes.


Behaviour and enzyme release by Anisakis sp. larvae (Nematoda: Ascaridida).
Anisakis sp. larvae when incubated in vitro produced secretions/excretions which released the dye from an azocoll substrate, indicating protease activity. The optimal conditions for enzyme release and activity were a temperature of 37 degrees C and a pH of 7.5. In addition the larvae showed peak behavioural activity at 37 degrees C, the body temperature of the final, marine mammalian host. The results are discussed in relation to their possible significance to the invasion of the various hosts in the life-cycle.


Discrimination in the health care system among higher-weight adults: evidence from a Canadian national cross-sectional survey.
Weight-related social stigma is associated with adverse health outcomes. Health care systems are not exempt of weight stigma, which includes stereotyping, prejudice and discrimination. The objective of this study was to examine the association between body mass index (BMI) class and experiencing discrimination in health care. We used data from the 2013 Canadian Community Health Survey, which included measurements of discrimination never collected previously on a national scale. Logistic regression analysis was used to assess the risk of self-reported discrimination in health care in adults (≥18 years) across weight categories: not obese (BMI < 30 kg/m2), obese class I (BMI = 30-< 35 kg/m2) and obese class II or III (BMI ≥ 35 kg/m2). One in 15 (6.4%; 95% CI: 5.7-7.0%) of the adult population reported discrimination in a health care setting (e.g. physician's office, clinic or hospital). Compared with those in the not obese group, the risk of discrimination in health care was somewhat higher among those in the class I obesity category (odds ratio [OR] = 1.20; 95% CI: 1.00-1.44) and significantly higher among those in class II/III (OR = 1.52; 95% CI: 1.21-1.91), after controlling for sex, age and other socioeconomic characteristics. Quantified experiences of weight-related discrimination underscore the need to change practitioner attitudes and practices as well as the policies and procedures of the health care system. More research is needed on the social and economic impacts of weight stigma to inform focused investments for reducing discrimination in the health care system as a microcosm of the society it reflects.


Characterization of a novel human UDP-GalNAc transferase, pp-GalNAc-T10.
A novel member of the human UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (pp-GalNAc-T) gene family was cloned as a homolog of human pp-GalNAc-T7, and designated pp-GalNAc-T10. pp-GalNAc-T10 transcript was found in the small intestine, stomach, pancreas, ovary, thyroid gland and spleen. In a polypeptide GalNAc-transfer assay, recombinant pp-GalNAc-T10 transferred GalNAc onto a panel of mucin-derived peptide substrates. Furthermore, pp-GalNAc-T10 demonstrated strong transferase activity with glycopeptide substrates.


Determination of hydrate inhibitor in crude oil by nanoextraction-gas chromatography.
This work focused on the quantitation of methanol as a hydrate inhibitor in crude oil. The novelty is nanoextraction of a polar compound from a complex non-polar matrix and selection of the proper fiber with maximum selectivity, loading percent, and lifetime. This approach not only does not require specific instrumentation, such as multiple columns and selective detectors, but also has eliminated the use of organic solvent and avoids the insertion of water inside the GC columns. The objective is optimization of extraction conditions, GC adjustments, and data processing. Experiments were conducted on the real sample of Iranian offshore crude oil by a carboxen/PDMS fiber via GC equipped with a cross-linked polyethylene glycol column and flame ionization detector. The results revealed that this fiber adsorbed the alcohols among other light non-polar compounds of crude oil. Moreover, the interference effects of ethanol were solved by proper selection of the thermal program. The LOD, LOQ, and linear range of this approach were determined to be 3.9, 12.9, and 14-229 ppm for methanol, respectively. Using the standard calibration and the standard addition methods, the relative errors of 1.6-7.2 and 5.3-14.0% were determined.


Computational Mechanisms Mediating Inhibitory Control of Coordinated Eye-Hand Movements.
Significant progress has been made in understanding the computational and neural mechanisms that mediate eye and hand movements made in isolation. However, less is known about the mechanisms that control these movements when they are coordinated. Here, we outline our computational approaches using accumulation-to-threshold and race-to-threshold models to elucidate the mechanisms that initiate and inhibit these movements. We suggest that, depending on the behavioral context, the initiation and inhibition of coordinated eye-hand movements can operate in two modes-coupled and decoupled. The coupled mode operates when the task context requires a tight coupling between the effectors; a common command initiates both effectors, and a unitary inhibitory process is responsible for stopping them. Conversely, the decoupled mode operates when the task context demands weaker coupling between the effectors; separate commands initiate the eye and hand, and separate inhibitory processes are responsible for stopping them. We hypothesize that the higher-order control processes assess the behavioral context and choose the most appropriate mode. This computational mechanism can explain the heterogeneous results observed across many studies that have investigated the control of coordinated eye-hand movements and may also serve as a general framework to understand the control of complex multi-effector movements.


Development and expert evaluation of "Moms on the Move," a physical activity intervention for WIC mothers. Women, Infants, and Children.
The purpose of this descriptive study was to develop and evaluate "Moms on the Move," a provider-counseled physical activity intervention for mothers enrolled in the Women, Infants, and Children (WIC) program. The intervention was based on the Transtheoretical Model (TTM) of behavior change. The evaluation occurred in two stages. In the first stage, physical activity behavioral experts (n=4) evaluated the: (a) rationale for intervention components; (b) linkages between behavior change constructs, intervention activities, and study outcomes; (c) literature support for the TTM behavior change constructs; and (d) the intervention brochure. The expert evaluation tool was adapted from the "Educational Materials Review Form." Each item in the expert evaluation met the <or= 3.0 mean criterion for acceptability (range, 1.33-2.67). Revisions were made based on expert comments before stage 2. In the second stage, WIC mothers (n=5) evaluated the intervention brochure. The 9-item WIC mothers' evaluation tool was adapted from a simple tool for community members. In the second stage evaluation, the mean total score for the intervention brochure evaluation was 44.0 (SD=1.22), which met the a priori criterion to retain as is. Mean item responses ranged from 4.8 to 5.0 (5.0=great). This evaluation indicates that "Moms on the Move" is a promising physical activity intervention for WIC mothers, which should be implemented for efficacy testing.


Single-incision laparoscopic transumbilical shunt placement.
Ventriculoperitoneal (VP) shunt placement is the most common surgical treatment for hydrocephalus. Laparoscopic techniques to aid in the placement of the peritoneal portion have been reported previously. Laparoscopic shunt placement has been associated with decreased operating time, less blood loss, and shorter hospital stays. The authors describe a single-incision laparoscopic shunt (SILS) insertion technique that facilitates directed placement of the peritoneal portion of the catheter in children. A total of 6 pediatric patients underwent the SILS procedure between December 2008 and March 2009. This cohort included 5 girls and 1 boy; the average age was 6 years (range 1 day-16 years). One patient had previously undergone a VP shunt placement, but all other patients were undergoing the initial creation of their shunt. The most common pathological condition encountered was posttraumatic hydrocephalus (2 patients). All patients underwent successful placement of the peritoneal catheters. All catheters were seen to have CSF flowing freely within the peritoneal space. The authors' recent experience shows that SILS placement is safe and feasible in children. It allows accurate, directed placement of the VP shunt with a single, almost invisible, umbilical incision. The shunt tubing is remote from this incision.


YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of Escherichia coli.
Bacterial cryptic prophage (defective prophage) genes are known to drastically influence host physiology, such as causing cell growth arrest or lysis, upon expression. Many phages encode lytic proteins to destroy the cell envelope. As natural antibiotics, only a few lysis target proteins were identified. ydfD is a lytic gene from the Qin cryptic prophage that encodes a 63-amino-acid protein, the ectopic expression of which in Escherichia coli can cause nearly complete cell lysis rapidly. The bacterial 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is responsible for synthesizing the isoprenoids uniquely required for sustaining bacterial growth. In this study, we provide evidence that YdfD can interact with IspG, a key enzyme involved in the MEP pathway, both in vivo and in vitro. We show that intact YdfD is required for the interaction with IspG to perform its lysis function and that the mRNA levels of ydfD increase significantly under certain stress conditions. Crucially, the cell lysis induced by YdfD can be abolished by the overexpression of ispG or the complementation of the IspG enzyme catalysis product methylerythritol 2,4-cyclodiphosphate. We propose that YdfD from the Qin cryptic prophage inhibits IspG to block the MEP pathway, leading to a compromised cell membrane and cell wall biosynthesis and eventual cell lysis.


The care and nurture of undulator data sets.
Undulator radiation is the X-ray source of choice for modern macromolecular crystallography beamlines. Here, the basic properties of undulator sources are described and it is indicated why they make such good X-ray sources for macromolecular crystallography. Collection of excellent data from these beamlines is not always straightforward; therefore, a number of rules are postulated for undulator data collection and guidelines are offered which will help to ensure a satisfactory experiment.


Identification of indole alkaloids of Catharanthus roseus with liquid chromatography/mass spectrometry using collision-induced dissociation with the thermospray ion repeller.
Fragmentation of protonated molecular ions produced from catharanthine, tabersonine, ajmalicine and serpentine in a high-performance liquid chromatography (HPLC) thermospray ion source was studied. Collision-induced dissociation (CID) of the compounds was achieved by merely increasing the repeller potential; i.e. no discharge current was applied and filament was not on. Proportion of fragments to the protonated molecular ions increased with the potential at the 180-350 V range studied, but overall yield of detected ions decreased at the higher voltages in all cases. Comparison of fragments produced in the thermospray CID with those derived from the protonated molecular ions by colliding with argon in a triple-stage quadrupole instrument showed that the fragmentation is very similar in both cases. An analytical application for identifying the alkaloids from plant cell culture material by HPLC/mass spectrometry using the thermospray CID is described.


Complete genome sequences of two insect-specific flaviviruses.
We determined the complete genomic sequences of two previously discovered insect-specific flaviviruses, Marisma mosquito virus (MMV) and Nanay virus (NANV), using a combination of high-throughput sequencing, reverse transcription-polymerase chain reaction, 5' and 3' rapid amplification of cDNA ends and Sanger sequencing. Complete polyprotein amino acid sequence alignments revealed that the closest known relatives of MMV and NANV are Donggang virus (89% identity, 95% similarity) and Nounané virus (53% identity, 70% similarity), respectively. Phylogenetic inference is in agreement with these findings. Potential programmed -1 ribosomal frameshifting sites were bioinformatically identified in the genomes of both viruses.


Neonatal intensive care practices harmful to the developing brain.
There has been a marked increase in the survival of extremely low birth weight (ELBW) infants, but these babies have a long stay in the NICU. Strategies to decrease their neurodevelopmental impairment become very important. The maximum development of the brain occurs between 29-41 weeks. From the warm, dark, acquatic econiche, where the baby hears pleasant sounds like the mother's heart beat, the baby suddenly finds itself in the dry, cold, excessively bright, noisy, environment of the NICU. Noise, bright light, painful procedures, and ill-timed caregiving activities, adversely affect the infant's development. Excessive radiation from X-rays of babies on the ventilator and CT scans also affect the brain. Medications like steroids for chronic lung disease also cause damage to the brain. Aminoglycides and frusemide are known to cause hearing impairment. Hence a developmentally supportive, humanized care will go a long way in enhancing the developmental outcome of these babies.


The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man.
1. The N-hydroxylation of dapsone is thought to be responsible for the methaemoglobinaemia and haemolysis associated with this drug. We wished to investigate the effect of concurrent administration of cimetidine (400 mg three times per day) on the disposition of a single dose (100 mg) of dapsone in seven healthy volunteers in order to inhibit selectively N-hydroxylation. 2. The AUC of dapsone (31.0 +/- 7.2 micrograms ml-1 h) was significantly increased (P less than 0.001) in the presence of cimetidine (43.3 +/- 8.8 micrograms ml-1 h). 3. Peak methaemoglobin levels observed after dapsone administration (2.5 +/- 0.6%) were significantly (P less than 0.05) reduced in the presence of cimetidine (0.98 +/- 0.35%). 4. The percentage of the dose excreted in urine as the glucuronide of dapsone hydroxylamine was significantly (P less than 0.05) reduced in the presence of cimetidine (34.2 +/- 9.3 vs 23.1 +/- 4.2%). 5. Concurrent cimetidine therapy might reduce some of the haematological side-effects of dapsone.


Vaccines against SARS-CoV-2 variants and future pandemics.
Vaccination continues to be the most effective method for controlling COVID-19 infectious diseases. Nonetheless, SARS-CoV-2 variants continue to evolve and emerge, resulting in significant public concerns worldwide, even after more than 2 years since the COVID-19 pandemic. It is important to better understand how different COVID-19 vaccine platforms work, why SARS-CoV-2 variants continue to emerge, and what options for improving COVID-19 vaccines can be considered to fight against SARS-CoV-2 variants and future pandemics. Here, we reviewed the innate immune sensors in the recognition of SARS-CoV-2 virus, innate and adaptive immunity including neutralizing antibodies by different COVID-19 vaccines. Efficacy comparison of the several COVID-19 vaccine platforms approved for use in humans, concerns about SARS-CoV-2 variants and breakthrough infections, and the options for developing future COIVD-19 vaccines were also covered. Owing to the continuous emergence of novel pathogens and the reemergence of variants, safer and more effective new vaccines are needed. This review also aims to provide the knowledge basis for the development of next-generation COVID-19 and pan-coronavirus vaccines to provide cross-protection against new SARS-CoV-2 variants and future coronavirus pandemics.


[Sensitivity to levofloxacin of Mycobacterium tuberculosis strains with various phenotype isolated from patients with newly diagnosed and chronic tuberculosis].
Susceptibility to levofloxacin of 56 strains of Mycobacterium tuberculosis, isolated from 22 patients with first estimated and 84 patients with chronic tuberculosis was investigated. Ratio of multi-drug resistance achieved 54.5 per cent in first group and 94.1 per cent in the second group. 23 (41.1 per cent) isolated strains belonged to individual genotypes, 33 (58.9 per cent)--to Beijing group. All mycobacteria isolates were sensitive to critical concentration of levofloxacin--10 mcg/mL. The results of the investigation proves the ability to recommend levofloxacin application at the patients with first estimated tuberculosis and at the patients with most hazardous tuberculosis pathogen of Beijing group.


Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.
The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.


Restless Leg Syndrome/Willis-Ekbom disease in women with iron deficiency anemia.
Restless Leg Syndrome (RLS) also known as Willis-Ekbom Disease (WED) is a common condition associated with reduced quality of life and other medical conditions, particularly cardiovascular diseases. Despite its common occurrence, it is widely underdiagnosed and undertreated. Therefore, identification of high-risk individuals for RLS/WED bears diagnostic and therapeutic significance. Iron deficiency anemia has a role in the pathophysiology of RLS/WED and both conditions have been reported to occur higher in females. In this study, the frequency of RLS/WED among women diagnosed with iron deficiency anemia was examined as well as laboratory variables that could guide the clinician in the diagnosis of RLS/WED. A total of 51 women attending to the department of internal medicine with complaints of fatigue and tiredness and diagnosed as having iron deficiency anemia were evaluated using the International Restless Leg Syndrome Study Group (IRLSSG) diagnostic criteria for RLS. Laboratory variables were recorded. The severity of RLS/WED was assessed using the RLS rating scale in patients diagnosed with RLS/WED. RLS/WED was diagnosed in 41.1% of the women with iron deficiency anemia. There were no significant differences between women with or without RLS /WED in terms of laboratory variables. Also, no correlations were observed between disease severity and laboratory variables. There is an 8 to 10-fold increase in the incidence of RLS/WED among women with iron deficiency anemia as compared to general population. Therefore, a possible diagnosis of RLS/WED should be kept in mind in all women with iron deficiency anemia.


Preclinical Optical Imaging to Study Pathogenesis, Novel Therapeutics and Diagnostics Against Orthopaedic Infection.
Preclinical in vivo optical imaging includes bioluminescence imaging (BLI) and fluorescence imaging (FLI), which provide noninvasive and longitudinal monitoring of biological processes in an in vivo context. In vivo BLI involves the detection of photons of light from bioluminescent bacteria engineered to naturally emit light in preclinical animal models of infection. Meanwhile, in vivo FLI involves the detection of photons of a longer emission wavelength of light after exposure of a fluorophore to a shorter excitation wavelength of light. In vivo FLI has been used in preclinical animal models to detect fluorescent-labeled host proteins or cells (often in engineered fluorescent reporter mice) to understand host-related processes, or to detect injectable near-infrared fluorescent probes as a novel approach for diagnosing infection. This review describes the use of in vivo optical imaging in preclinical models of orthopaedic implant-associated infection (OIAI), including (i) pathogenesis of the infectious course, (ii) monitoring efficacy of antimicrobial prophylaxis and therapy and (iii) evaluating novel near-infrared fluorescent probes for diagnosing infection. Finally, we describe optoacoustic imaging and fluorescence image-guided surgery, which are recent technologies that have the potential to translate to diagnosing and treating OIAI in humans. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2269-2277, 2019.


High prevalence and expression of antiseptic resistance genes among infectious t037/ST239 methicillin-resistant Staphylococcus aureus (MRSA) strains in North Khorasan Province, Iran.
Staphylococcus aureus is an important infectious agent and the majority of methicillin-resistant S. aureus (MRSA) infections are of nosocomial origin. To define the level and distribution of antiseptic resistance among infectious S. aureus strains we studied MRSA and methicillin-susceptible S. aureus (MSSA) isolates collected from different infection sites in an assortment of patients. S. aureus isolates were investigated for in vitro susceptibility to antiseptic agents and detection of qacA/B, smr, vanA, and mecA genes. Among the S. aureus isolates we studied, 25 and 41 were MRSA and MSSA, respectively. The mean of minimum inhibitory concentrations (MICs) for benzethonium chloride (BTC) among MRSA was statistically significantly higher than for MSSA (26 µg/ml versus 11.7 µg/ml, P=0.003) while there was no significant difference between MRSA and MSSA for benzalkonium chloride (BKC) and chlorhexidine digluconate (CHG). The qacA/B genes were carried in 68% of the MRSA and 58.2% of MSSA (P=0.601), while smr was carried in 39% of MRSA and 29.3% of MSSA strains (P=1.000). In 15 out of 25 cases, MRSA ST239 with spa types t037, t030, and t7688 was isolated from the infection site with 86.6% of them carrying a resistance gene (qacA/B or qacA/B + smr). The frequent presence of antiseptic resistance genes and a consequently elevated MIC against antiseptics among ST239 MRSA emphasizes the importance of mandatorily monitoring MRSA for effective infection control.


Characteristics and fabrication of vertical type organic light emitting transistor using dimethyldicyanoquinonediimine (DMDCNQI) as a n-type active layer and light emitting polymer.
We have investigated electrical properties of vertical type organic transistor using dimethyldicyanoquinonediimine (DMDCNQI) as a n-type active layer. And also, the contact resistance Ro for charge injection from a metal electrode to an organic semiconductor layer was studied by transfer line method. The radiance of organic light emitting transistor (OLET) consisting of glass/ITO (drain)/PEDOT:PSS/MEH-PPV/DMDCNQI/Al (gate)/DMDCNQI/Au (source) can be effectively controlled by applying gate voltage like depletion mode.


Multi-sectoral health promotion and public health: the role of evidence.
Evidence-informed health promotion and public health is an emerging and ever-changing theme in research and practice. A collaborative approach to gathering and applying evidence is crucial to implementing effective multi-sectoral health promotion and public health interventions for improved population outcomes. This paper presents an argument for the development of multi-sector evidence and discusses both facilitators and challenges to this process. Sector-specific contacts familiar with decision-making processes were selected from referrals gained through academic, government and non-government networks and interviewed (in-person or via telephone) as part of a small scale study to scope the use of evidence within non-health sectors where decisions are likely to impact on public health. The views gathered are preliminary, and this analysis would benefit from more extensive consultation. Nonetheless, information gathered from the interviews and literature search provide valuable insights into evidence-related decision-making paradigms which demonstrate similarities with, and differences from, those found in the health sector. Decisions in health promotion and public may benefit from consideration of the ways in which disciplines and sectors can work together to inform policy and practice.


Bilateral Adrenal Hyperplasia Due to Adrenocorticotropic Hormone-Secreting Esthesioneuroblastoma on FDG PET and 111In-Pentetreotide Scintigraphy.
A 53-year-old woman with metastatic esthesioneuroblastoma was referred for FDG PET/CT imaging. FDG PET/CT showed symmetrical uptake in bilaterally enlarged adrenal glands, in addition to abnormal uptake in bone and lymph node metastases. In-pentetreotide scintigraphy was further performed and revealed the lack of adrenal uptake. The patient's serum adrenocorticotropic hormone (ACTH) level was extremely high, suggesting that hyperplastic condition in the adrenal glands due to ACTH stimulation from the metastatic esthesioneuroblastoma was responsible for increased FDG uptake. The combination of FDG PET and In-pentetreotide scintigraphy was useful for the pathophysiological evaluation of ACTH-secreting esthesioneuroblastoma.


Crystallization and preliminary structure determination of the plant food allergen Pru av 2.
Thaumatin-like proteins (TLPs) have mostly been investigated in the context of their function as pathogenesis-related proteins and only in recent years have some of them been classified as allergens. Here, the purification and crystallization of the first allergenic TLP, Pru av 2, a 23.3 kDa protein isolated from ripe cherries, is reported. The crystals diffracted to 2.1 A resolution at a rotating-anode generator and were found to belong to space group P2(1), with unit-cell parameters a = 44.48, b = 41.04, c = 59.16 A, beta = 106.61 degrees and one molecule per asymmetric unit. In order to obtain high-resolution data, an annealing protocol was applied that improved the resolution limit from 1.6 to 1.3 A at a synchrotron.


[Operative treatment of genital prolapse of the female: pros and cons of mesh materials].
The development of different mesh materials has led to an improvement of the individual surgical correction of genital prolapse. Macroporous monofilamentous synthetic meshes seem to be the optimal material in case of recurrent prolapse or of severe insufficiency of the pelvic floor. The use of biological meshes shows a markedly better tolerance with fewer infections or erosions despite the lack of evidence-based information on their long-term efficacy and safety. The surgical correction of genital prolapse has to carefully consider all risks and benefits in order to improve quality of life. In this respect, mesh materials can be particularly advantageous in the recurrent situation.


On the taxonomy of the genera Stigmatophora Staudinger, 1881 and Miltochrista Hübner, [1819], with description of a new species from North Thailand and China (Lepidoptera, Erebidae, Arctiinae, Lithosiini).
The generic group names Cymella Felder, 1874 and Myclela Watson, Fletcher Nye, 1980 are excluded from the subtribe Nudariina and synonymized with the nominate subgenus of the genus Stigmatophora Staudinger, 1881 belonging to the subtribe Endrosiina. The type species of Cymella and Myclela, Cymella congerens Felder, 1874 is synonymized with the nominate subspecies of Stigmatophora (Stigmatophora) rhodophila (Walker, [1865]). The type locality of Cymella congerens is designated as Shanghai (E China). Two taxa previously treated as synonyms of S. congerens are upgraded to the species level and left in the genus Miltochrista Hübner, [1819]: Miltochrista artocarpi (Moore, 1878), stat. nov. and Miltochrista roseogrisea (Rothschild, 1913), stat. nov. The genus Asuropsis Matsumura, 1927 is excluded from the synonymy of Miltochrista and synonymized with the nominate subgenus of the genus Stigmatophora. The new combination is established: Stigmatophora (Stigmatophora) ranruna (Matsumura, 1927), comb. nov. A new species, Stigmatophora (Stigmatophora) cernyi Volynkin, sp. n. is described from North Thailand and Southwest China. Adults of both sexes of all the species mentioned and their genitalia are illustrated.


[Computer-aided surgery planning for implantation of artificial ear].
In conventional ear implantation surgery, clinical physicians usually make a surgery planning based on their observation on series of 2D X-ray images or CT images. Such a planning method requires the physicians to have a high level of clinical experience. Besides, the whole operation is unintuitive, and might have certain risk. Considering these facts, we have developed a computer-aided system for the surgery planning of the implantation of artificial ear based on CT imaging and 3D reconstruction techniques. The system effectively overcomes the main drawbacks in conventional surgery planning techniques, and it makes the surgery planning procedure more precise, safe, and intuitive.


Clinical analysis of emergency exploratory laparotomy in patients with intractable postpartum hemorrhage.
This study was performed to explore the causes and clinical characteristics of emergency exploratory laparotomy in patients with intractable postpartum hemorrhage. This retrospective study was performed from January 2004 to December 2017. Patients with intractable postpartum hemorrhage were grouped according to the initial pathogenesis as determined by exploratory laparotomy: uterine atony, placental factors, coagulation dysfunction, or uterine rupture. This study involved 72 patients who underwent emergency exploratory laparotomy, accounting for 0.04% of total deliveries. Uterine preservation surgery and hysterectomy were performed in 31 and 41 patients, respectively. Abnormal events upon returning to the ward were primarily vaginal hemorrhage and pelvic hematoma. The frequency of uterine artery ligation was lower in the hysterectomy group than uterine preservation group. The prothrombin activity level, fibrinogen level, and platelet count before surgery were lower in the hysterectomy group than uterine preservation group. The international normalized ratio and activated partial thromboplastin time were higher in the hysterectomy group than uterine preservation group. In total, 44 patients developed complications. Placental implantation is a primary cause of hysterectomy after emergency laparotomy. However, the possibility of postpartum hemorrhage caused by coagulation disorders should not be ignored.


HETEROCARYOSIS-LIKE PHENOMENON IN BACILLUS SUBTILIS.
Ikeda, Y. (University of Tokyo, Tokyo, Japan) and T. Iijima. Heterocaryosis-like phenomenon in Bacillus subtilis. J. Bacteriol. 83:1025-1028. 1962.-When a mixture of methionine-dependent, histidine-dependent, streptomycin-resistant cells and tryptophan-dependent, streptomycin-sensitive cells of Bacillus subtilis K is plated on minimal medium supplemented with asparagine and streptomycin, tiny colonies consisting of both component cells and X-type cells appear at a frequency of about 10(-6). Because the X-type cell segregates persistently both components and X-type, even after spore formation, it is considered to be a heterocaryon or a syncaryon possessing two kinds of genomes in a common cytoplasm.


Effect of growth and recovery temperatures on pressure resistance of Listeria monocytogenes.
Experimental conditions can affect the outcome of bacterial stress-tolerance assays. Growth conditions that optimize microbial recovery should be established to help evaluate the effectiveness of treatment conditions for food safety. The objectives of this study were to determine the effects of growth and recovery temperatures on pressure resistance of early stationary-phase Listeria monocytogenes in milk. The tested conditions were the following: (1) L. monocytogenes was grown at various temperatures (10, 15, 20, 25, 30, 35, 40 and 43 degrees C), suspended in ultra-high temperature (UHT) -processed whole milk, pressure-treated at 400 MPa for 2 min at 21 degrees C and recovered on Tryptic Soy Agar supplemented with 0.6% yeast extract (TSAYE) at 35 degrees C; (2) L. monocytogenes was grown at 35 and 43 degrees C, pressure treated in milk (400 and 500 MPa, respectively, for 2 min at 21 degrees C) and recovered on TSAYE at various temperatures (4, 10, 15, 20, 25, 30, 35 and 40 degrees C); (3) L. monocytogenes originally grown at 35 degrees C, was pressure treated in milk (400 or 450 MPa for 2 min at 21 degrees C), and recovered on TSAYE at 10 degrees C for various time intervals (1, 2, 3, 6, 9 and 12 days) then at 35 degrees C for 5 days. There was no significant difference (P>0.05) in pressure-resistance of L. monocytogenes grown at 10 to 25 degrees C with approximately 6.5-log CFU/ml population reductions. At growth temperatures greater than 25 degrees C, pressure resistance increased with less than 1-log CFU/ml reduction observed for L. monocytogenes originally grown at 43 degrees C. After pressure treatment, regardless of growth temperature and pressure treatment, the greatest recovery of L. monocytogenes was within the 4 to 20 degrees C range; maximum recovery at 10 degrees C required approximately 24 days. The time for comparable post-pressure treatment recovery could be reduced by incubation at 10 degrees C for at least 2 days followed by incubation at 35 degrees C for 5 days. The findings of the present study indicate that growth and recovery temperatures affect the pressure resistance of L. monocytogenes and should, therefore, be taken into account when assessing the adequacy of inactivation treatments.


Using transcriptomic and metabolomic data to investigate the molecular mechanisms that determine protein and oil contents during seed development in soybean.
Soybean [Glycine max (L.) Merri.] is one of the most valuable global crops. And vegetable soybean, as a special type of soybean, provides rich nutrition in people's life. In order to investigate the gene expression networks and molecular regulatory mechanisms that regulate soybean seed oil and protein contents during seed development, we performed transcriptomic and metabolomic analyses of soybean seeds during development in two soybean varieties that differ in protein and oil contents. We identified a total of 41,036 genes and 392 metabolites, of which 12,712 DEGs and 315 DAMs were identified. Analysis of KEGG enrichment demonstrated that DEGs were primarily enriched in phenylpropanoid biosynthesis, glycerolipid metabolism, carbon metabolism, plant hormone signal transduction, linoleic acid metabolism, and the biosynthesis of amino acids and secondary metabolites. K-means analysis divided the DEGs into 12 distinct clusters. We identified candidate gene sets that regulate the biosynthesis of protein and oil in soybean seeds, and present potential regulatory patterns that high seed-protein varieties may be more sensitive to desiccation, show earlier photomorphogenesis and delayed leaf senescence, and thus accumulate higher protein contents than high-oil varieties.


A scalable intermediate representation for remote interaction with soft tissues.
A scalable, internet aware "intermediate representation" has been developed for remote interactive simulation of large deformable models. Further a networked computational environment is presented in which commodity computers tele-connect to remote high end servers using real-time protocol to utilize their processing power to enable highly realistic and detailed simulation of surgical scenarios. This proposed intermediate representation ("hive" (set) of computational nodes associated with surgical tool tip) can be tuned to the computational capacity of the client computer and is also scalable to the quality of the available network resources (bandwidth, delay, delay jitter) for the connection between client and server.


Novel Nomogram for Preoperative Prediction of Early Recurrence in Intrahepatic Cholangiocarcinoma.
Introduction: The emerging field of "radiomics" has considerable potential in disease diagnosis, pathologic grading, prognosis evaluation, and prediction of treatment response. We aimed to develop a novel radiomics nomogram based on radiomics features and clinical characteristics that could preoperatively predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy. Methods: A predictive model was developed from a training cohort comprising 139 ICC patients diagnosed between January 2010 and June 2014. Radiomics features were extracted from arterial-phase image of contrast-enhanced magnetic resonance imaging. Feature selection and construction of a "radiomics signature" were through Spearman's rank correlation and least absolute shrinkage and selection operator (LASSO) logistic regression. Combined with clinical characteristics, a radiomics nomogram was developed with multivariable logistic regression. Performance of the nomogram was evaluated with regard to discrimination, calibration, and clinical utility. An independent validation cohort involving 70 patients recruited from July 2014 to March 2016 was used to evaluate the utility of the nomogram developed. Results: The radiomics signature, consisting of nine features, differed significantly between ER patients and non-ER patients in training and validation cohorts. The area under the curve (AUC) of the radiomics signature in training and validation cohorts was 0.82 (confidence interval [CI], 0.74-0.88) and 0.77 (95% CI, 0.65-0.86), respectively. The AUC of the radiomics nomogram combining the radiomics signature and clinical stage in the two cohorts was 0.90 (95%CI, 0.83-0.94) and 0.86 (95% CI, 0.76-0.93), respectively. Decision curve analysis confirmed the clinical usefulness of the radiomics nomogram. Conclusion: The non-invasive radiomics nomogram developed using the radiomics signature and clinical stage could be used to predict ER of ICC after partial hepatectomy.


Ocular inhibitory effects of the dopamine DA2 agonist (Ha-118) in cats and rabbits.
1. Topical administration of the dopamine (DA2) receptor agonist, Ha-118, produced unilateral ocular hypotension and miosis in normal cats. 2. The ocular hypotensive and mitotic effects of Ha-118 were not observed in surgically sympathectomized cats indicating that an intact sympathetic pathway is necessary to demonstrate activity. 3. Ha-118 caused dose-dependent suppression of contractions of the cat nictitating membrane (CNM) elicited by electrical stimulation of the pre- and postganglionic sympathetic nerve trunks but not by exogenously administered noradrenaline suggesting that Ha-118 affected prejunctional but not ganglionic or postjunctional receptors. 4. Sulpiride antagonized Ha-118-induced inhibition of neuronally mediated contractions in the CNM suggesting an interaction at DA2 receptors. 5. Topical administration of Ha-118 inhibited the rise in intraocular pressure induced by oral water loading in rabbits. 6. Topical pretreatment with metoclopramide, a DA2 antagonist, inhibited the ocular antihypertensive effect of Ha-118 in rabbits. 7. These studies demonstrate that Ha-118 decreased intraocular pressure (IOP) and pupil diameter (PD) in the cat and that this activity can be correlated with suppression of peripheral sympathetic tone in the CNM.


Sagging Eye Syndrome or Nemaline Rod Myopathy? Divergence Insufficiency with Levator Dehiscence as an Overlapping Symptom between Two Diagnoses.
A 78-year-old woman complained of gradual, painless onset of horizontal binocular diplopia associated with progressive axial weakness. Physical examination revealed esotropia that was greater at distance than at near vision, bilateral levator dehiscence, and normal abducting saccadic speeds. Given the age of the patient and compatible clinical findings, the diagnosis of Sagging Eye Syndrome (SES) was made. However, further work-up with a muscle biopsy suggested Sporadic Late-Onset Nemaline Myopathy (SLONM) as the cause of her progressive muscle weakness. Although rare, external ophthalmoplegia has been described in the literature as a presenting symptom in SLONM. To elucidate the pathological mechanism for the patient's diplopia, an MRI of the orbits was performed, which revealed findings consistent with SES. This case aims to highlight the importance of integrating clinical findings during the diagnostic process and serves as a reminder that diplopia can be a common symptom for an uncommon diagnosis.


Modulation of the contractility of micropatterned myocardial cells with nanoscale forces using atomic force microscopy.
The ability to modulate cardiomyocyte contractility is important for bioengineering applications ranging from heart disease treatments to biorobotics. In this study, we examined the changes in contraction frequency of neonatal rat cardiomyocytes upon single-cell-level nanoscale mechanical stimulation using atomic force microscopy. To measure the response of same density of cells, they were micropatterned into micropatches of fixed geometry. To examine the effect of the substrate stiffness on the behavior of cells, they were cultured on a stiffer and a softer surface, glass and poly (dimethylsiloxane), respectively. Upon periodic cyclic stimulation of 300 nN at 5 Hz, a significant reduction in the rate of synchronous contraction of the cell patches on poly(dimethylsiloxane) substrates was observed with respect to their spontaneous beat rate, while the cell patches on glass substrates maintained or increased their contraction rate after the stimulation. On the other hand, single cells mostly maintained their contraction rate and could only withstand a lower magnitude of forces compared to micropatterned cell patches. This study reveals that the contraction behavior of cardiomyocytes can be modulated mechanically through cyclic nanomechanical stimulation, and the degree and mode of this modulation depend on the cell connectivity and substrate mechanical properties.


Case report: recovery and reorganization after congenital unilateral brain damage.
Recovery and neural reorganization after congenital left- and right-brain injury is assessed on dichotic listening and tachistoscopic visuo-perceptual tasks. A matched-pair approach for age and type of lesion is used. Over-all, deficits are less pronounced than in adults. Innate specialization of both left and right hemispheres is supported by the data. In addition, a left-right maturational gradient is suggested by the all-around better performance of the child with left-hemisphere pathology. The later maturing, relatively less-committed right hemisphere is better able to compensate after unilateral injury.


Modeling and closed-loop pharmacologic control of the ventricular rate during induced atrial fibrillation in anesthetized dogs.
An automated drug delivery system that provides closed-loop feedback control of the ventricular rate during atrial fibrillation is described. The control system was designed using a mathematical model of the effect of esmolol infusion in the ventricular rate. The model was developed in system identification experiments with anesthetized dogs in which atrial fibrillation was induced and maintained by rapid atrial pacing. A control system of variable structure, which incorporates a transient controller and a regulator, was designed to perform satisfactorily over a wide range of subject responses to drug infusion. The transient controller brings the ventricular rate to the setpoint with little overshoot. When the ventricular rate is near the setpoint, the drug infusion rate is calculated by the regulator. The drug infusion rate is constrained to ensure smooth transitions in the hemodynamic state of the patient and for safety. Feasibility of the system was demonstrated in computer simulations and animal experiments.


Development of a PEGylated-Based Platform for Efficient Delivery of Dietary Antioxidants Across the Blood-Brain Barrier.
The uptake and transport of dietary antioxidants remains the most important setback for their application in therapy. To overcome the limitations, a PEGylated-based platform was developed to improve the delivery properties of two dietary hydroxycinnamic (HCA) antioxidants-caffeic and ferulic acids. The antioxidant properties of the new polymer-antioxidant conjugates (PEGAntiOxs), prepared by linking poly(ethylene glycol) (PEG) to the cinnamic acids by a one-step Knovenagel condensation reaction, were evaluated. PEGAntiOxs present a higher lipophilicity than the parent compounds (caffeic and ferulic acids) and similar, or higher, antioxidant properties. PEGAntiOxs were not cytotoxic at the tested concentrations in SH-SY5Y, Caco-2, and hCMEC/D3 cells. By contrast, cytotoxic effects in hCMEC/D3 and SH-SY5Y cells were observed, at 50 and 100 μM, for caffeic and ferulic acids. PEGAntiOxs operate as antioxidants against several oxidative stress-cellular inducers in a neuronal cell-based model, and were able to inhibit glycoprotein-P in Caco-2 cells. PEGAntiOxs can cross hCMEC/D3 monolayer cells, a model of the blood-brain barrier (BBB) endothelial membrane. In summary, PEGAntiOxs are valid antioxidant prototypes that can uphold the antioxidant properties of HCAs, reduce their cytotoxicity, and improve their BBB permeability. PEGAntiOxs can be used in the near future as drug candidates to prevent or slow oxidative stress associated with neurodegenerative diseases.


Mechanistic features of the atypical tRNA m1G9 SPOUT methyltransferase, Trm10.
The tRNA m1G9 methyltransferase (Trm10) is a member of the SpoU-TrmD (SPOUT) superfamily of methyltransferases, and Trm10 homologs are widely conserved throughout Eukarya and Archaea. Despite possessing the trefoil knot characteristic of SPOUT enzymes, Trm10 does not share the same quaternary structure or key sequences with other members of the SPOUT family, suggesting a novel mechanism of catalysis. To investigate the mechanism of m1G9 methylation by Trm10, we performed a biochemical and kinetic analysis of Trm10 and variants with alterations in highly conserved residues, using crystal structures solved in the absence of tRNA as a guide. Here we demonstrate that a previously proposed general base residue (D210 in Saccharomyces cerevisiae Trm10) is not likely to play this suggested role in the chemistry of methylation. Instead, pH-rate analysis suggests that D210 and other conserved carboxylate-containing residues at the active site collaborate to establish an active site environment that promotes a single ionization that is required for catalysis. Moreover, Trm10 does not depend on a catalytic metal ion, further distinguishing it from the other known SPOUT m1G methyltransferase, TrmD. These results provide evidence for a non-canonical tRNA methyltransferase mechanism that characterizes the Trm10 enzyme family.


Comparison of a quantum random number generator with pseudorandom number generators for their use in molecular Monte Carlo simulations.
Four pseudorandom number generators were compared with a physical, quantum-based random number generator using the NIST suite of statistical tests, which only the quantum-based random number generator could successfully pass. We then measured the effect of the five random number generators on various calculated properties in different Markov-chain Monte Carlo simulations. Two types of systems were tested: conformational sampling of a small molecule in aqueous solution and liquid methanol under constant temperature and pressure. The results show that poor quality pseudorandom number generators produce results that deviate significantly from those obtained with the quantum-based random number generator, particularly in the case of the small molecule in aqueous solution setup. In contrast, the widely used Mersenne Twister pseudorandom generator and a 64-bit Linear Congruential Generator with a scrambler produce results that are statistically indistinguishable from those obtained with the quantum-based random number generator. © 2017 Wiley Periodicals, Inc.


Blood Culture Negative Endocarditis: A Review of Laboratory Diagnostic Approaches.
Infective endocarditis is a potentially fatal condition, and identifying the pathogen is crucial to optimizing antibiotic treatment. While a blood culture takes time and may yield negative results, it remains the gold standard for diagnosis, blood culture-negative endocarditis, which accounts for up to 20% of infective endocarditis cases, poses a clinical challenge with increasing mortality. To better understand the etiology of blood culture-negative infective endocarditis, we reviewed non-culture-based strategies and compared the results. Serology tests work best in limited pathogens, such as Coxiella burnetii and Bartonella infections. Most of the pathogens identified by broad-range PCR tests are Streptococcus spp, Staphylococcus spp and Propionibacterium spp. adding specific real-time PCR assays to the systematic PCR testing of patients with blood culture-negative endocarditis will increase the efficiency of diagnosis. Recently, metagenomic next-generation sequencing has also shown promising results.


Diagnostic Accuracy of Four Commercial Triplex Immunochromatographic Tests for Rapid Detection of Rotavirus, Adenovirus, and Norovirus in Human Stool Samples.
Noroviruses (NoV), rotaviruses (RVA), and adenoviruses (AdV) are the main viral agents responsible for acute gastroenteritis (AGE) in humans. We aimed to determine the diagnostic accuracy of four commercial immunochromatographic tests (ICTs) intended for the rapid and simultaneous detection of these three pathogens. Diagnostic accuracy of bioNexia Noro/Rota-Adeno (bioMérieux), Immunoquick NoRotAdeno (Biosynex), Rota+Adeno+Noro combo card (CerTest Biotec), and Rida Quick Rota/Adeno/Noro Combi (R-Biopharm) ICTs was assessed retrospectively using a collection of 160 stool specimens (including 43 RVA-, 47 AdV-, and 42 NoV-positive samples) from French patients with AGE and using molecular methods as the reference standard. For RVA, the four ICTs demonstrated similar high sensitivity (93%) and excellent specificity (97.4 to 100%). For AdV, the four ICTs demonstrated similar poor sensitivity (54.3 to 58.7%) but excellent specificity (95.5 to 100%). They performed the best in AdV-F species (sensitivity, 80.8 to 84.6%) and worst in AdV non-F species (sensitivity, 22.2 to 27.8%). For NoV, the Rida Quick Rota/Adeno/Noro combi ICT exhibited high sensitivity (87.5%), but the sensitivity of the three others was poor (42.5 to 47.5%). The four ICTs exhibited high specificity (96.6 to 99.1%). Diagnostic accuracy was genogroup dependent. When we tested genogroup I NoV, the Rida Quick Rota/Adeno/Noro Combi ICT presented high sensitivity (90%), while the three other ICTs presented poor sensitivity (10 to 30%); when we tested genogroup II NoV, sensitivity was similar for the four ICTs (65 to 85%). In conclusion, the four ICTs are suitable first-line tests for the rapid diagnosis of RVA infections. The four ICTs are not suitable for the routine diagnosis of AdV infections but could provide a rapid response in case of positivity, notably in the context of AGE. Only the Rida Quick Rota/Adeno/Noro Combi ICT is suitable for the rapid detection of NoV, while the sensitivity for the detection of genogroup I NoV needs to be improved for the 3 other ICTs before being implemented in the routine diagnosis of NoV.


Volatilization of contaminants from suspended sediment in a water column during dredging.
Remedial dredging of contaminated bed sediments in rivers and lakes results in the suspension of sediment solids in the water column, which can potentially be a source for evaporation of hydrophobic organic compounds (HOCs) associated with the sediment solids. Laboratory experiments were conducted in an oscillating grid chamber to simulate the suspension of contaminated sediments and flux to air from the surface of the water column. A contaminated field sediment from Indiana Harbor Canal (IHC) and a laboratory-inoculated University Lake (UL) sediment, Baton Rouge, LA, were used in the experiments, where water and solids concentration and particle size distribution were measured in addition to contaminant fluxes to air. A transient model that takes into account contaminant desorption from sediment to water and evaporation from the water column was used to simulate water and sediment concentrations and air fluxes from the solids suspension. In experiments with both sediments, the total suspended solids (TSS) concentration and the average particle diameter of the suspended solids decreased with time. As expected, the evaporative losses were higher for compounds with higher vapor pressure and lower hydrophobicity. For the laboratory-inoculated sediment (UL), the water concentrations and air fluxes were high initially and decreased steadily implying that contaminant release to the water column from the suspended solids was rapid, followed by evaporative decay. For the field sediments (IHC), the fluxes and water concentrations increased initially and subsequently decreased steadily. This implied that the initial desorption to water was slow and that perhaps the presence of oil and grease and aging influenced the contaminant release. Comparison of the model and experimental data suggested that a realistic determination of the TSS concentration that can be input into the model was the most critical parameter for predicting air emission rates.


Qualitative and Quantitative Analysis of Six Fatty Acid Amides in 11 Edible Vegetable Oils Using Liquid Chromatography-Mass Spectrometry.
Fatty acid amides (FAAs) are endogenous lipid molecules that exhibit various physiological activities. FAAs are usually present at nanomolar levels in biological samples. In this study, a method for the qualitative and quantitative determination of six FAAs (linoleamide, linoleoyl ethanolamide, oleoyl ethanolamide, palmitic amide, oleamide, and octadecanamide) in edible vegetable oils was established. All six FAAs were detected in sesame, peanut, soybean (decolorized and non-decolorized), and blended oils; five in sunflower oil; four in rice oil; three in linseed and olive oils; and two in corn and canola oils. The total contents of FAAs were highest in sesame oil (104.88 ± 3.01 μg/mL), followed by peanut oil (34.96 ± 3.87 μg/mL), soybean oil (16.75 ± 1.27 μg/mL), and blended oil (13.33 ± 0.77 μg/mL), and the contents in the other edible vegetable oils were all <1.03 μg/mL. The concentrations of linoleoyl ethanolamide and oleoyl ethanolamide were highest in non-decolorized soybean oil, while the other four FAAs (linoleamide, palmitic amide, oleamide, and octadecanamide) showed the highest concentrations in sesame oil. The total contents of these FAAs in eight different oils were higher than those in biological fluids and tissue. Our study confirmed that edible vegetable oils are rich in FAAs, and provides reliable data for evaluating the nutritive value of vegetable oils.


[Red cell system and selected red cell enzymes in men occupationally exposed to mercury vapours].
Determination of erythrocyte number and their indices and enzymatic activity of: glucose-6-phosphate dehydrogenase (G-6PD), superoxide dismutase (SOD), acetylcholinesterase (AchE), glutathione reductase (GR) and hexokinase (Hx) in peripheral blood erythrocytes of workers chronically exposed to mercury vapours during the production of chloride (the mercuric electrolysis method). The studied workers were equipment operators, electricians and electrolysis maintenance men at the chloride production department using the mercuric electrolysis method. The study involved 46 men, aged 21 to 56, (x = 39 +/- 10.4) exposed to mercury vapours for the period from 7 months to 32 years (x = 14.7+/-10.8), working in a three shift system, for 8 hours a day. Smokers constituted 50% of the studied group (23 men). Urine mercury concentrations of workers exposed to mercury vapours were in the range from 10 to 215 microg/dm3 (x = 81,4 +/- 72,9) and in blood in range 4 do 72 microg/dm3 (x=16.3 +/- 15,0). Controls were 46 men aged 20-54, (x=33.6 +/- 9.8), workers and voluntary blood donors, who never experienced occupational exposure to mercury vapours or other chemicals, and to physical agents. The percentage of smokers in the control group was 34.7% (16 men). Basic haematological determinations (hematocrit - Hct, Hb concentration, erythrocyte number in mm3 of blood, mean red cell hemoglobin concentration (MCHC), mean red cell volume (MCV) and enzymatic studies (activity of G-6PD, SOD, AchE, GR, Hx) in peripheral blood samples obtained from workers and controls were performed. Hematological parameters of the peripheral blood were determined using AVL 808 hematological counter, following the manufacturer's instructions. Activity of the studied enzymes was estimated by the spectrophotometric method described by Beutler, following the recommendations of the International Committee for Standardisation in Hematology. Values of Ht were higher in all the subgroups exposed to Hg workers (divided according to duration of exposure or urine mercury concentrations) in comparison to the control group. The erythrocyte number in mm3 of peripheral blood was also higher in the exposed workers group than in controls. MCHC in the total group exposed to mercury vapours was lower than in the controls. In the subgroup exposed to mercury vapours for < 10 years, the value of this parameter was lower than in the control group; whereas in the subgroups separated in respect to mercury concentration in the urine, it was lower only in workers showing the highest urine concentration of this metal. In workers exposed to mercury vapours, MCV index values were lower than in the controls. In the subgroups of workers who smoked and those who did not smoke, they were also lower than in the controls; whereas in the group of the longest exposed workers from 21 to 35 years, it was found to be higher than in controls. The activity of G6PD was lower in the group of subjects occupationally exposed to mercury vapours than in the control group - 5.60 +/- 1.60 and 7.41 +/- 0.43 IU/gHb respectively. When comparing the subgroups of smokers and non-smokers with the controls, workers showed lower G6PD activity than in the matching control subgroups - 6.24 +/- 1.97 and 7.44 +/-0.22 IU/gHb in the subgroups of smokers and 4.97 +/- 0.72 and 7.38 +/- 0.18 IU/gHb in non-smokers respectively. Erythrocyte G6PD activity was lower in all studied groups separated in respect to exposure time - 5.54 +/- 1.75, 6.02 +/- 2.05 and 5.54 +/- 1.05 IU/gHb respectively. The same pattern of changes was observed in the subgroups separated in respect to mercury concentration in the urine compared to the controls. The lowest enzyme activity was found in the subgroups showing the highest mercury concentration in the urine wnen compared with the subgroup with the lowest urine concentration of this metal - 5.19 +/- 1.50 and 6.00 +/- 1.84 IU/gHb respectively SOD activity in the group of workers exposed to mercury was lower compared to the controls - 2289.97 +/- 122.31 and 2418.03 +/- 60.28 IU/gHb respectively. The smoking and non-smoking workers showed respective SOD activities on - 2305.43 +/- 102.75 and 2274.50 +/- 124.5 IU/gHb; whereas in the matching subgroup of controls - 2452.11 +/- 88.72 and 2382.09 +/- 91.22 IU/gHb, respectively. The activity of this enzyme in all investigated groups selected in respect to length of employment, revealed lower values when compared with the controls - 2271.20 +/- 115.23 in the group with under 10 years of exposure, 2335.11 +/-167.71 IU/gHb in those exposed for 11-20 years, and 2290.40 +/- 26.12 IU/gHb in the subgroup exposed for the longest period of time. Similar changes were observed in the activity of this enzyme in the subgroups separated in respect to mercury concentration in the urine when SOD activity was compared with the controls. The AchE activity was higher in the group exposed to mercury vapours compared to the controls and the respective values were - 50.22 +/- 14.44 and 36.87 +/- 2.92 IU/gHb. In the subgroups separated in respect to length of exposure, the activity of this enzyme was statistically significantly higher than in the control group. The GR activity levels were lower in the exposed group - 8.01 +/-2.54 IU/gHb, compared to the controls - 10.24 +/- 1.24 IU/gHb. In the subgroups of smokers and non-smokers, GR activity was lower, 8.48 +/- 2.37 and 7.54 +/- 2.68 IU/gHb, compared to smokers and non-smokers in the control group, 10.26 +/- 1.01 and 10.16 +/- 1.03 IU/gHb, respectively. The GR activity was also statistically significantly lower in all groups separated in respect to duration of exposure, with the values of 8.56 +/-2.39, 8.26 +/- 2.38, 7.06 +/- 2.75 IU/gHb, respectively in subject groups and 10.24 +/- 1.35 in the control group. Similar changes were noticed in the subgroup separated in respect to mercury concentration in the urine. The Hx activity was lower in the group exposed to mercury vapours - 1.08 +/-0.11. compared with the controls - 1.21 +/- 0.16 IU/gHb. The enzyme activity showed a similar pattern in the subgroups separated in respect to duration of exposure when they were compared with the control group. Exposure to mercury vapours present changes in the red blood cells, manifested by increased (when compared with the control group), number of erythrocytes in peripheral and decreased mean cell volume and mean cell hemoglobin concentration values, as well as changes in the metabolic processes occurring in the erythrocytes. In subjects exposed to mercury vapours some metabolic processes may be additionally modified by addiction to cigarette smoking.


Social and ecological correlates of space use patterns in Bwindi mountain gorillas.
Space use patterns determine access to resources necessary for survival and reproduction. Although it is recognized that the interplay between social and ecological variables shapes spacing patterns, few studies in group-living animals have simultaneously assessed their importance in a comprehensive approach using different spatiotemporal space use measures. In territorial species, such patterns are strongly determined by between-group competition, but its impact in non-territorial species is poorly understood. To better understand the role of social and ecological variables in non-territorial mountain gorillas (Gorilla beringei beringei), we simultaneously evaluated the impact of between-group competition (local gorilla population density and frequency of intergroup encounters) and within-group competition (group size) on space use patterns in 13 gorilla groups in Bwindi Impenetrable National Park, Uganda, while also examining variation in food availability (herbaceous food availability and level of frugivory). We found evidence of between-group competition, indicated by a decline of both monthly home range size and frequency of revisits to each part of the home range as the local gorilla population density increased and by an increase in daily travel distance on days when intergroup encounters occurred. Within-group feeding competition was inferred by a decrease in the frequency of revisits as group size increased. Lastly, food availability influenced the gorillas' spacing patterns, as indicated by a decline in monthly home range size as herbaceous food availability increased and by an increase in daily travel distance as the degree of frugivory increased. In sum, our results suggest that Bwindi gorillas adapted their space use according to the constraints of intraspecific competition and the availability of food resources. We provide some of the first evidence of between-group competition influencing spacing patterns in a non-territorial species. This study suggests a gradient between territoriality and non-territoriality, along which the level of between-group competition varies.


Nomogram based on a circular RNA biomarker for predicting the likelihood of successful sperm retrieval via microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia.
Many circular RNAs (circRNAs) are specifically expressed in the testes and seminal plasma of patients with non-obstructive azoospermia (NOA), highlighting them as potential predictors of microdissection testicular sperm extraction (micro-TESE) outcomes. Although research has indicated that circular RNA monoglyceride lipase (circ_MGLL) is highly expressed in the testicular tissues of patients with NOA, the association between circ_MGLL expression and sperm retrieval outcomes (SROs) in patients with idiopathic non-obstructive azoospermia (iNOA) receiving micro-TESE remains unclear. This single-center, retrospective cohort study enrolled 114 patients with iNOA who underwent micro-TESE at Northwest Women's and Children's Hospital from January 2017 to November 2021. A logistic regression model was used to examine associations between SRO and circ_MGLL expression in testicular tissues, the results of which were used in conjunction with previous findings to establish a nomogram. The predictive performance of the circ_MGLL-based nomogram was evaluated via calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA) using an internal validation method. The generalized additive model indicated that the probability of successful SRO for micro-TESE decreased as circ_MGLL expression increased in testicular tissues. Across the entire cohort, univariate logistic regression analysis revealed that circ_MGLL expression was inversely associated with SRO in patients with NOA. This trend did not change after stratification according to age, body mass index, testicular volume, follicle-stimulating hormone (FSH) level, luteinizing hormone (LH) level, testosterone (T) level, or pathological type (or after adjusting for these confounders) (odds ratio <1, P < 0.001). A nomogram was then generated by integrating circ_MGLL, pathological types, and FSH, LH, and T levels. The circ_MGLL-based predictive model achieved satisfactory discrimination, with an area under the curve of 0.857, and the calibration curves demonstrated impressive agreement. The DCA indicated that the net clinical benefit of the circ_MGLL-based predictive model was greater than that of circ_MGLL alone. circ_MGLL is significantly associated with the SRO of micro-TESE in patients with iNOA. The circ_MGLL-based nomogram developed in the current study can predict successful SRO with high accuracy.


Effects of the Chinese herbal medicine Hong Huang decoction, on myocardial injury in breast cancer patients who underwent anthracycline-based chemotherapy.
To assess the effects of Hong Huang Decoction (HHD), a Chinese herbal medicine, on myocardial injury in breast cancer patients who underwent anthracycline (ANT)-based chemotherapy. A total of 51 patients with breast cancer who underwent an ANT-based chemotherapy program and met the inclusion/exclusion criteria were allocated to the treatment or placebo groups using a random number generation process. Patients in the treatment group received liquid HHD twice a day. Treatment was given from 1 day prior to chemotherapy up to the end of chemotherapy (after 6 months). Participants in the placebo group received a placebo over the same schedule. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diagnostic markers of acute myocardial infarction [e.g., lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and B-type natriuretic peptide (BNP)], nitric oxide (NO), superoxide dismutase (SOD), as well as pro-inflammatory cytokines [e.g., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and human C-reactive protein (CRP)], and anti-inflammatory cytokine interleukin-10 (IL-10), were outcome measures assessed before chemotherapy, 3 and 6 months after chemotherapy. Compared to the placebo group, the GLS value was significantly higher in the treatment group (19.95 ± 1.16 vs. 19.06 ± 1.64, P ≤ 0.001). Significant differences were also noted for levels of SOD (689.71 ± 203.60 vs. 807.88 ± 182.10, P < 0.05), IL-6 (58.04 ± 22.06 vs. 194.20 ± 40.14, P ≤ 0.001), IL-10 (237.90 ± 94.98 vs. 68.81 ± 32.92, P ≤ 0.001), NO (75.05 ± 26.39 vs. 55.83 ± 19.37, P ≤ 0.005), and TNF-α (301.80 ± 134.20 vs. 680.30 ± 199.60, P ≤ 0.001) in the patients before chemotherapy compared to 6 months after initiating chemotherapy. HHD regulated the levels of IL-6, IL-10, SOD, NO, and TNF-α. The results demonstrated that GLS is a better indicator of early myocardial injury compared to LVEF, and HHD could modulate oxidative stress to protect against ANT cardio toxicity. Chinese Clinical Trial Registry, identifier ChiCTR1900022394. Date of registration: 2019-04-09.


Estrogenic activity of isoflavonoids from Onobrychis ebenoides.
Fractionation of the neutral extract of Onobrychis ebenoides (Leguminosae) yielded a new isoflavone, named ebenosin (1), in addition to the known ones, afrormosin (2), formononetin (3) and daidzein (4). Although the relative binding affinities of 1 - 4 for estrogen receptor alpha (ERalpha) were nearly comparable and matched those of 1-3 for ERbeta, that of 4 for the latter receptor was significantly higher than any of the other. Compounds 1 - 4 induced cell proliferation and gene expression in breast and endometrial cancer cells in an ER-dependent manner. Nonetheless, the rank order of induction potencies ( 4 > 3 >or= 2 >or= 1) matched better that of affinities for ERbeta ( 4 > 3 >or= 2 >or= 1) rather than ERalpha ( 4 >or= 3 >or= 2 >or= 1). While the antiestrogen ICI 182,780 could inhibit the induction of proliferation of ER-positive breast cancer cells by 1-4, it could not prevent 1 from exhibiting significant ER-independent cytotoxicity at 10 microM. By contrast, 1 was much less cytotoxic and only weakly estrogenic for ER-positive endometrial adenocarcinoma cells. In conclusion, our data suggest that the C-8 isoprenyl substituent of 1 renders it cytotoxic and/or estrogenic in a cell-dependent manner.


Prevalence and Determinants of Susceptibility to Tobacco Smoking Among Students in The Gambia.
Smoking is the biggest preventable cause of death and kills about seven million people annually. As smoking prevalence is falling in developed countries, tobacco businesses are turning to low- and middle-income countries (LMICs) to generate new tobacco markets. To prevent young people from initiating smoking and becoming regular smokers, it is important to understand the causes of susceptibility to smoking. In this study, we report a nationwide survey of the prevalence and risk factors of smoking susceptibility among students aged 12-20 years in The Gambia. We used two-stage cluster random sampling to select students in secondary schools throughout The Gambia and questionnaire to collect data on demographic characteristics and indicators on susceptibility to initiating smoking. Among the total sample of 10289 students, 9831 (96%; 55.6% girls and 44.4% boys, aged 12-20 years) nonsmokers were included in the analysis. Of these, 3333 (33.9%) were found to be susceptible to smoking. Smoking susceptibility was more common among students attending grant-aided schools, non-Muslims, who had smoking allowed at home, had family members or friends who smoke, were sent to purchase cigarettes, had poor knowledge of the harmful effects of smoking, noticed point-of-sale tobacco advertisements, and who had positive attitudes towards smoking. This study shows that susceptibility to smoking is common among students and associated with preventable exposures. Although based on cross-sectional data, these findings suggest that raising students' awareness of the harmful effects of smoking and reducing the prevalence of adult smoking, extending tobacco advertising restrictions to include point-of-sale, are all important to preventing the uptake of smoking among students. This is the first study to provide detailed data on smoking susceptibility and risk factors in a nationally representative sample of young people in The Gambia. Our findings show that susceptibility to smoking is relatively high and associated with preventable measures. Our results also identify an urgent need to broaden the ban on tobacco advertising to explicitly include point-of-sale advertisements. These findings provide valuable information for tobacco control policies and evidence to enable targeted intervention for young people most at risk of initiating smoking.


[KID syndrome, pachydermatoglyphy and Dandy-Walker syndrome].
We report a case of KID syndrome in a young girl born to non-consanguinous parents without any similar family history. The typical features of this dysplasia, erythrokeratodermia with dry rugous teguments, pachydermia folds of the knees, facial erythema, peribuccal grooves, leucokeratosic perleche, hypotrichosis of the eye lashes and eyebrows, early onset deafness and ophtalmological lesions were observed. The characteristic pachydermatoglyphia of the hands was present. A malformation of the posterior cerebral fossa--a dandy walker syndrome--was revealed at computed tomography.


Use of Mass Cytometry to Profile Human T Cell Exhaustion.
Mass cytometry has become an important technique for the deep analysis of single cell protein expression required for precision systems immunology. The ability to profile more than 40 markers per cell is particularly relevant for the differentiation of cell types for which low parametric characterization has proven difficult, such as exhausted CD8+ T cells (TEX). TEX with limited effector function accumulate in many chronic infections and cancers and are subject to inhibitory signaling mediated by several immune checkpoints (e.g., PD-1). Of note, TEX represent considerable targets for immune-stimulatory therapies and are beginning to be recognized as a major correlate of successful checkpoint blockade approaches targeting the PD-1 pathway. TEX exhibit substantial functional, transcriptomic and epigenomic differences compared to canonical functional T cell subsets [such as naïve (TN), effector (TEFF) and memory T cells (TMEM)]. However, phenotypic distinction of TEX from TEFF and TMEM can often be challenging since many molecules expressed by TEX can also be expressed by effector and memory T cell populations. Moreover, significant heterogeneity of TEX has been described, such as subpopulations of exhausted T cells with progenitor-progeny relationships or populations with different degrees of exhaustion or homeostatic potential that may directly inform about disease progression. In addition, TEX subsets have essential clinical implications as they differentially respond to antiviral and checkpoint therapies. The precise assessment of TEX thus requires a high-parametric analysis that accounts for differences to canonical T cell populations as well as for TEX subset heterogeneity. In this review, we discuss how mass cytometry can be used to reveal the role of TEX subsets in humans by combining exhaustion-directed phenotyping with functional profiling. Mass cytometry analysis of human TEX populations is instrumental to gain a better understanding of TEX in chronic infections and cancer. It has important implications for immune monitoring in therapeutic settings aiming to boost T cell immunity, such as during cancer immunotherapy.


Use of fibrinogen and thrombin sponge in pediatric split liver transplantation.
To analyze the use of this sponge in pediatric patients undergoing split-liver transplantation. Retrospective study, including 35 pediatric patients undergoing split-liver transplantation, divided into two groups according to the use of the sponge: 18 patients in Group A (no sponge) and 17 in Group B (with sponge). The characteristics of recipients and donors were similar. We observed greater number of reoperation due to bleeding in the wound area in Group A (10 patients - 55.5%) than in Group B (3 patients - 17.6%); p = 0.035. The median volume of red blood cells transfused in Group A was significantly higher (73.4 ± 102.38 mL/kg) than that in Group B (35.1 ± 41.67 mL/kg); p = 0.048. Regarding bile leak there was no statistical difference. The use of the human fibrinogen and thrombin sponge, required lower volume of red blood cell transfusion and presented lower reoperation rates due to bleeding in the wound area.


Exploring the Factors Triggering Occupational Ethics Risk of Technology Transaction in Chinese Construction Industry.
: The importance of occupational ethics risk considerations during technology transaction in the construction industry is acknowledged. This is particularly in that the industry plays a significant part in a nation's development. The technology transaction has seen an increase in activity due to massive infrastructure development programmers adopted by governments and increase in external investment. The technology transaction, like any other, is not immune to unethical occupational behavior. This study aims to investigate the source of occupational ethics risk during technology transaction in the Chinese construction industry. A review of literature demonstrated that a number of contextual factors can influence unethical occupational risk practices. In total, 130 engineering practitioners took part in a questionnaire survey to explore the source of occupational ethics risk during the technology transaction in the Chinese construction industry. Firstly, there were 25 factors identified through literature review overall, which were sorted and analyzed. Among the twenty-five factors, three were identified as the most significant factors: Unreasonable incentives for technology trading; poor regulation; and asymmetry of information. Then, through exploratory factor analysis (EPA) method, the twenty-five factors were divided into seven groups: legal environment, industry environment, incompleteness of information, asymmetry of information, difficulty of observation of information, differences between the two sides of cooperation, and incorrect conceptual awareness. This study provided an added dimension to the understanding of occupational ethics risk issues during the technology transaction in the Chinese construction industry. This paper therefore contributes to the list of countries where similar studies have been undertaken.


Doublet Ground State in a Vanadium(II) Complex: Redox and Coordinative Noninnocence of Tripodal Ligand Architecture.
We report on the geometric and electronic structures of a series of V2+/3+ tren-bridged iminopyridine complexes [tren = tris(2-aminoethyl)amine] that enable the observation of an unexpected doublet ground state for a nominally 3d3 species. Tren undergoes condensation reactions with picolinaldehyde or methyl-6-formylnictonate to form the respective tripodal ligand sets of (py)3tren and (5-CO2Mepy)3tren. The (py)3tren ligand is coordinated to V2+ and V3+ metal centers to form complex salts [1-H](OTf)2 and [1-H](OTf)3, respectively (OTf- = CF3SO3-). For [1-H]2+, strong metal-ligand π-covalency with respect to the V2+ (3d3) and iminopyridine ligands weakens its interelectronic repulsion. For [1-H]3+, the bridgehead nitrogen of the tren scaffold forms a seventh coordinate covalent bond with a V3+ (3d2) metal center. The coordination of (5-CO2Mepy)3tren to a V2+ metal center results in the redox noninnocent and heptacoordinate compound [1-CO2Me](OTf)2 with a doublet (S = 1/2) ground state that we support with magnetic susceptibility and spectroscopy measurements. The complexes are uniformly characterized experimentally with single-crystal X-ray diffraction, electronic absorbance, and electrochemistry, and electronic structures are corroborated by computational techniques. We present a new computational procedure that we term the spin-optimized approximate pair (SOAP) method that enables the visualization and quantification of electron-electron interactions.


Personality, biographical characteristics, and job interview success: a longitudinal study of the mediating effects of interviewing self-efficacy and the moderating effects of internal locus of causality.
In this study, the authors developed and tested a model of performance in job interviews that examines the mediating role of interviewing self-efficacy (I-SE; job applicants' beliefs about their interviewing capabilities) in linking personality and biographical background with interview success and the moderating role of locus of causality attributions in influencing the relationship between interview success and subsequent I-SE. The authors tested their model (over 5 months' duration) with matched data from 229 graduating seniors, firms, and university records. Hierarchical regression analyses demonstrated I-SE mediated the effects of Extraversion, Conscientiousness, and leadership experience on interview success. Locus of causality attributions for interview outcomes moderated the relationship between interview success and subsequent I-SE. Theoretical and practical implications are discussed.


Effects of Progressive Additional Lenses on Binocular Vision in Children with Pseudophakia.
Binocular vision may be compromised in children after unilateral cataract surgery because the distances at which clear vision is present are different for the two eyes. We believe that wearing progressive additional lenses can be effective in improving the binocular vision in children with pseudophakia.


Accessibility, nature and quality of health information on the Internet: a survey on osteoarthritis.
This study aims to determine the quality and validity of information available on the Internet about osteoarthritis and to investigate the best way of sourcing this information. Keywords relevant to osteoarthritis were searched across 15 search engines representing medical, general and meta-search engines. Search engine efficiency was defined as the percentage of unique and relevant websites from all websites returned by each search engine. The quality of relevant information was appraised using the DISCERN tool and the concordance of the information offered by the website with the available evidence about osteoarthritis determined. A total of 3443 websites were retrieved, of which 344 were identified as unique and providing information relevant to osteoarthritis. The overall quality of website information was poor. There was no significant difference between types of search engine in sourcing relevant information; however, the information retrieved from medical search engines was of a higher quality. Fewer than a third of the websites identified as offering relevant information cited evidence to support their recommendations. Although the overall quality of website information about osteoarthritis was poor, medical search engines may provide consumers with the opportunity to source high-quality health information on the Internet. In the era of evidence-based medicine, one of the main obstacles to the Internet reaching its potential as a medical resource is the failure of websites to incorporate and attribute evidence-based information.


Secondary traumatization of wives of war veterans with posttraumatic stress disorder.
To determine the symptoms of secondary traumatic stress and possible influences of demographic and socioeconomic factors on the occurrence of secondary traumatic stress in wives of war veterans with posttraumatic stress disorder (PTSD). The study included 56 wives of war veterans diagnosed with PTSD and treated at the Center for Psychotrauma in Rijeka, Croatia. A short structured interview was conducted with each woman to collect demographic and socioeconomic data. The women independently completed an adapted 16-item version of Indirect Traumatization Questionnaire to determine the presence of secondary traumatic stress symptoms, which corresponded with PTSD symptoms as defined by the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders. Out of 56 veterans' wives included in the study, 32 had six or more symptoms of secondary traumatic stress, whereas only 3 had none of the symptoms. Twenty-two women met the diagnostic criteria for secondary traumatic stress. Women with secondary traumatic stress were married longer than those without it (mean+/-standard deviation, 19.1+/-9.1 vs 13.2+/-7.8 years, respectively; P=0.016). Eleven of 22 women with secondary traumatic stress and 8 of 34 women without secondary traumatic stress were unemployed (P=0.05). As more than a third of war veterans wives met the criteria for secondary traumatic stress, any treatment offered to veterans with PTSD must address the traumatization of their family.


Cytotoxicity of N6-cycloalkylated adenine and adenosine analogs to mouse hepatoma cells.
Cytotoxic effect(s) of N6-cycloalkylated adenine and adenosine derivatives, upon the viability of mouse hepatoma cells, were studied in vitro. N6-Cyclopropyl- and N6-cyclobutyladenine and adenosine derivatives (33 micrograms/ml; 24-48 h) exerted significant cytotoxic effects upon the cells. N6-Cyclopentyl- and N6-cyclohexyladenines exerted similar effects under different experimental conditions (133-166 micrograms/ml; 48-72 h), while no significant cytotoxic effect(s) were observed with the corresponding adenosine derivatives under these conditions. Observed physical changes in the treated cells included cell elongation, short stubby filaments, wide intracellular spaces and ruptured cell membranes. N6-Cycloalkylated nucleosides were usually more cytotoxic than the cycloalkylated bases.