Effectiveness of training to promote routine enquiry for domestic violence by midwives and nurses: A pre-post evaluation study.

BACKGROUND: Asking women about experiences of domestic violence in the perinatal period is accepted best practice. However, midwives and nurses may be reluctant to engage with, or effectively respond to disclosures of domestic violence due a lack of knowledge and skills. AIM: To evaluate the impact of training on knowledge and preparedness of midwives and nurses to conduct routine enquiry about domestic violence with women during the perinatal period. METHOD: A pre-post intervention design was used. Midwives and nurses (n=154) attended a full day workshop. Of these, 149 completed pre-post workshop measures of knowledge and preparedness. Additional questions at post-training explored participants' perceptions of organisational barriers to routine enquiry, as well as anticipated impact of training on their practice. Training occurred between July 2015 and October 2016. FINDINGS: Using the Wilcoxon signed-rank test, all post intervention scores were significantly higher than pre intervention scores. Knowledge scores increased from a pre-training mean of 21.5-25.6 (Z=-9.56, p<0.001) and level of preparedness increased from 40.8 to 53.2 (Z=-10.12, p<0.001). Most participants (93%) reported improved preparedness to undertake routine enquiry after training. Only a quarter (24.9%) felt their workplace allowed adequate time to respond to disclosures of DV. CONCLUSIONS: Brief training can improve knowledge, preparedness, and confidence of midwives and nurses to conduct routine enquiry and support women during the perinatal period. Training can assist midwives and nurses to recognise signs of DV, ask women about what would be helpful to them, and address perceived organisational barriers to routine enquiry. Practice guidelines and clear referral pathways following DV disclosure need to be implemented to support gains made through training

Acute Ethanol Administration Rapidly Increases Phosphorylation of Conventional Protein Kinase C in Specific Mammalian Brain Regions in Vivo

Background Protein kinase C (PKC) is a family of isoenzymes that regulate a variety of functions in the central nervous system including neurotransmitter release, ion channel activity, and cell differentiation. Growing evidence suggests that specific isoforms of PKC influence a variety of behavioral, biochemical, and physiological effects of ethanol in mammals. The purpose of this study was to determine whether acute ethanol exposure alters phosphorylation of conventional PKC isoforms at a threonine 674 (p-cPKC) site in the hydrophobic domain of the kinase, which is required for its catalytic activity. Methods Male rats were administered a dose range of ethanol (0, 0.5, 1, or 2 g/kg, intragastric) and brain tissue was removed 10 minutes later for evaluation of changes in p-cPKC expression using immunohistochemistry and Western blot methods. Results Immunohistochemical data show that the highest dose of ethanol (2 g/kg) rapidly increases p-cPKC immunoreactivity specifically in the nucleus accumbens (core and shell), lateral septum, and hippocampus (CA3 and dentate gyrus). Western blot analysis further showed that ethanol (2 g/kg) increased p-cPKC expression in the P2 membrane fraction of tissue from the nucleus accumbens and hippocampus. Although p-cPKC was expressed in numerous other brain regions, including the caudate nucleus, amygdala, and cortex, no changes were observed in response to acute ethanol. Total PKC? immunoreactivity was surveyed throughout the brain and showed no change following acute ethanol injection

Time for T? Immunoinformatics addresses the challenges of vaccine design for neglected tropical and emerging infectious diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere

Primordial Black Holes: sirens of the early Universe

Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

Nonlinear vortex light beams supported and stabilized by dissipation

We describe nonlinear Bessel vortex beams as localized and stationary solutions with embedded vorticity to the nonlinear Schr\"odinger equation with a dissipative term that accounts for the multi-photon absorption processes taking place at high enough powers in common optical media. In these beams, power and orbital angular momentum are permanently transferred to matter in the inner, nonlinear rings, at the same time that they are refueled by spiral inward currents of energy and angular momentum coming from the outer linear rings, acting as an intrinsic reservoir. Unlike vortex solitons and dissipative vortex solitons, the existence of these vortex beams does not critically depend on the precise form of the dispersive nonlinearities, as Kerr self-focusing or self-defocusing, and do not require a balancing gain. They have been shown to play a prominent role in "tubular" filamentation experiments with powerful, vortex-carrying Bessel beams, where they act as attractors in the beam propagation dynamics. Nonlinear Bessel vortex beams provide indeed a new solution to the problem of the stable propagation of ring-shaped vortex light beams in homogeneous self-focusing Kerr media. A stability analysis demonstrates that there exist nonlinear Bessel vortex beams with single or multiple vorticity that are stable against azimuthal breakup and collapse, and that the mechanism that renders these vortexes stable is dissipation. The stability properties of nonlinear Bessel vortex beams explain the experimental observations in the tubular filamentation experiments.Comment: Chapter of boo

Antidepressant stimulation of CDP-diacylglycerol synthesis does not require monoamine reuptake inhibition

<p>Abstract</p> <p>Background</p> <p>Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol.</p> <p>Results</p> <p>Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with <it>p</it>-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues.</p> <p>Conclusion</p> <p>Antidepressants probably induce the activity of CDP-diacylglycerol synthase leading to increased production of CDP-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. Phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of BDNF signaling and neurogenesis. Hence, the present findings should strengthen the notion that modulation of brain phosphatidylinositide signaling probably contributes to the molecular mechanism of diverse antidepressant medications.</p

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

The all-particle spectrum of primary cosmic rays in the wide energy range from 10^14 eV to 10^17 eV observed with the Tibet-III air-shower array

We present an updated all-particle energy spectrum of primary cosmic rays in a wide range from 10^14 eV to 10^17 eV using 5.5 times 10^7 events collected in the period from 2000 November through 2004 October by the Tibet-III air-shower array located at 4300 m above sea level (atmospheric depth of 606 g/cm^2). The size spectrum exhibits a sharp knee at a corresponding primary energy around 4 PeV. This work uses increased statistics and new simulation calculations for the analysis. We performed extensive Monte Carlo calculations and discuss the model dependences involved in the final result assuming interaction models of QGSJET01c and SIBYLL2.1 and primary composition models of heavy dominant (HD) and proton dominant (PD) ones. Pure proton and pure iron primary models are also examined as extreme cases. The detector simulation was also made to improve the accuracy of determining the size of the air showers and the energy of the primary particle. We confirmed that the all-particle energy spectra obtained under various plausible model parameters are not significantly different from each other as expected from the characteristics of the experiment at the high altitude, where the air showers of the primary energy around the knee reaches near maximum development and their features are dominated by electromagnetic components leading to the weak dependence on the interaction model or the primary mass. This is the highest-statistical and the best systematics-controlled measurement covering the widest energy range around the knee energy region.Comment: 19 pages, 20 figures, accepted by Ap

In vitro effects of zinc on the cytokine production from peripheral blood mononuclear cells in patients with zinc allergy.

Metals, such as nickel, cobalt, chromium and zinc, are ubiquitous in the environment. Systemic reactions, including hand dermatitis and generalized eczematous reactions, can be caused by the dietary ingestion of metals. In this study, we aimed to determine whether the cytokine production from peripheral blood mononuclear cells (PBMCs) obtained from zinc allergy patients can be used as a sensitive marker to investigate zinc-allergic contact dermatitis. The diagnosis of sensitivity to metal was made based on the results of a metal patch test. The PBMCs were stimulated with various concentrations (5-100 μM) of zinc sulfate (ZnSO4) for 24 h. The culture supernatants were collected and analyzed using ELISA for measurement of the cytokine production. The levels of IFN-γ, TNF-α, IL-1β, IL-5, IL-13 and MIF were significantly higher in the zinc-allergic patients (n = 5) than in the healthy controls (n = 5) at 100 μM of ZnSO4 stimulation. Although, patch testing is considered as standard test to diagnose metal allergy but false-positive and -negative reactions may limit its use in conditions of existing dermatitis. Therefore, this study suggest that in support of patch testing the determination of cytokine production using PBMCs cultures would be helpful for making an early diagnosis of such conditions

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium