What Interrupts Suicide Attempts in Men: A Qualitative Study

Despite higher rates of suicide in men, there is a dearth of research examining the perspectives and experiences of males at risk of suicide, particularly in terms of understanding how interventions can be tailored to men’s specific needs. The current study aimed to examine factors assisting, complicating or inhibiting interventions for men at risk, as well as outlining the roles of family, friends and others in male suicide prevention. Thirty-five male suicide survivors completed one-to-one interviews, and forty-seven family and friends of male suicide survivors participated in eight focus groups. Thematic analysis revealed five major themes: (1) development of suicidal behaviours tends to follow a common path associated with specific types of risk factors (disrupted mood, unhelpful stoic beliefs and values, avoidant coping strategies, stressors), (2) men at risk of suicide tend to systematically misinterpret changes in their behaviour and thinking, (3) understanding mood and behavioural changes in men enables identification of opportunities to interrupt suicide progression, (4) distraction, provision of practical and emotional supports, along with professional intervention may effectively interrupt acute risk of harm, and (5) suicidal ideation may be reduced through provision of practical help to manage crises, and helping men to focus on obligations and their role within families. Findings suggest that interventions for men at risk of suicidal behaviours need to be tailored to specific risk indicators, developmental factors, care needs and individuals’ preferences. To our knowledge this is the first qualitative study to explore the experiences of both suicidal men and their family/friends after a suicide attempt, with the view to improve understanding of the processes which are effective in interrupting suicide and better inform interventions for men at risk.     

Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stoichiometry

Background

The human immunodeficiency virus type 1 (HIV-1) Vpu protein degrades CD4 and counteracts a restriction factor termed tetherin (CD317; Bst-2) to enhance virion release. It has been suggested that both functions can be genetically separated by mutation of a serine residue at position 52. However, recent data suggest that the S52 phosphorylation site is also important for the ability of Vpu to counteract tetherin. To clarify this issue, we performed a comprehensive analysis of HIV-1 with a mutated casein kinase-II phosphorylation site in Vpu in various cell lines, primary blood lymphocytes (PBL), monocyte-derived macrophages (MDM) and ex vivo human lymphoid tissue (HLT).

Results

We show that mutation of serine 52 to alanine (S52A) entirely disrupts Vpu-mediated degradation of CD4 and strongly impairs its ability to antagonize tetherin. Furthermore, casein-kinase II inhibitors blocked the ability of Vpu to degrade tetherin. Overall, Vpu S52A could only overcome low levels of tetherin, and its activity decreased in a manner dependent on the amount of transiently or endogenously expressed tetherin. As a consequence, the S52A Vpu mutant virus was unable to replicate in macrophages, which express high levels of this restriction factor. In contrast, HIV-1 Vpu S52A caused CD4+ T-cell depletion and spread efficiently in ex vivo human lymphoid tissue and PBL, most likely because these cells express comparably low levels of tetherin.

Conclusion

Our data explain why the effect of the S52A mutation in Vpu on virus release is cell-type dependent and suggest that a reduced ability of Vpu to counteract tetherin impairs HIV-1 replication in macrophages, but not in tissue CD4+ T cells.     

Characterization of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> Beijing isolates from the Mediterranean area

Background  

The Beijing lineage of Mycobacterium tuberculosis is causing concern due to its global distribution and its involvement in severe outbreaks. Studies focused on this lineage are mainly restricted to geographical settings where its prevalence is high, whereas those in other areas are scarce. In this study, we analyze Beijing isolates in the Mediterranean area, where this lineage is not prevalent and is mainly associated with immigrant cases.     

In situ adaptive response to climate and habitat quality variation: spatial and temporal variation in European badger (Meles meles) body weight

Variation in climatic and habitat conditions can affect populations through a variety of mechanisms, and these relationships can act at different temporal and spatial scales. Using post‐mortem badger body weight records from 15 878 individuals captured across the Republic of Ireland (7224 setts across ca. 15 000 km²; 2009–2012), we employed a hierarchical multilevel mixed model to evaluate the effects of climate (rainfall and temperature) and habitat quality (landscape suitability), while controlling for local abundance (unique badgers caught/sett/year). Body weight was affected strongly by temperature across a number of temporal scales (preceding month or season), with badgers being heavier if preceding temperatures (particularly during winter/spring) were warmer than the long‐term seasonal mean. There was less support for rainfall across different temporal scales, although badgers did exhibit heavier weights when greater rainfall occurred one or 2 months prior to capture. Badgers were also heavier in areas with higher landscape habitat quality, modulated by the number of individuals captured per sett, consistent with density‐dependent effects reducing weights. Overall, the mean badger body weight of culled individuals rose during the study period (2009–2012), more so for males than for females. With predicted increases in temperature, and rainfall, augmented by ongoing agricultural land conversion in this region, we project heavier individual badger body weights in the future. Increased body weight has been associated with higher fecundity, recruitment and survival rates in badgers, due to improved food availability and energetic budgets. We thus predict that climate change could increase the badger population across the Republic of Ireland. Nevertheless, we emphasize that, locally, populations could still be vulnerable to extreme weather variability coupled with detrimental agricultural practice, including population management.     

Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients

Background

Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam.

Methods/Design

This is an observational pharmacokinetic study of patients with trauma (cefazolin) or with sepsis (piperacillin-tazobactam). Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration of the antibiotic. Participants will be administered sinistrin, indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes resulting from pathology. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters of antibiotics.

Discussion

The study will describe cefazolin and piperacillin-tazobactam concentrations in plasma and the interstitial fluid of tissues in trauma and sepsis patients respectively. The results of this study will guide clinicians to effectively dose these antibiotics in order to maximize the concentration of antibiotics in the interstitial fluid of tissues.     

The relation between cartilage biomarkers (C2C,C1,2C,CS846, and CPII) and the long-term outcome of rheumatoid arthritis patients within the CAMERA trial

Introduction  

The aim of this study was to investigate whether serum biomarker levels of C2C, C1,2C, CS846, and CPII can predict the long-term course of disease activity and radiographic progression early in the disease course of rheumatoid arthritis (RA).     

A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord

Many oligodendrocytes in the spinal cord are derived from a region of the ventral ventricular zone (VZ) that also gives rise to motoneurons. Cell fate specification in this region depends on sonic hedgehog (Shh) from the notochord and floor plate. There have been suggestions of an additional source(s) of oligodendrocytes in the dorsal spinal cord. We revisited this idea by Cre-lox fate-mapping in transgenic mice. We found that a subpopulation of oligodendrocytes is generated from the Dbx1-expressing domain of the VZ, spanning the dorsoventral midline. Dbx-derived oligodendrocytes comprise less than 5% of the total; they are formed late during embryogenesis by transformation of radial glia and settle mainly in the lateral white matter. Development of Dbx-derived oligodendrocytes in vitro can occur independently of Shh but requires FGF signalling. Dbx-expressing precursors also generate astrocytes and interneurons, but do not contribute to the ependymal layer of the postnatal spinal cord.     

Personality-dependent dispersal: characterization, ontogeny and consequences for spatially structured populations

Dispersal is one of the most fundamental components of ecology, and affects processes as diverse as population growth, metapopulation dynamics, gene flow and adaptation. Although the act of moving from one habitat to another entails major costs to the disperser, empirical and theoretical studies suggest that these costs can be reduced by having morphological, physiological or behavioural specializations for dispersal. A few recent studies on different systems showed that individuals exhibit personality-dependent dispersal, meaning that dispersal tendency is associated with boldness, sociability or aggressiveness. Indeed, in several species, dispersers not only develop behavioural differences at the onset of dispersal, but display these behavioural characteristics through their life cycle. While personality-dependent dispersal has been demonstrated in only a few species, we believe that it is a widespread phenomenon with important ecological consequences. Here, we review the evidence for behavioural differences between dispersers and residents, to what extent they constitute personalities. We also examine how a link between personality traits and dispersal behaviours can be produced and how personality-dependent dispersal affects the dynamics of metapopulations and biological invasions. Finally, we suggest future research directions for population biologists, behavioural ecologists and conservation biologists such as how the direction and the strength of the relationship between personality traits and dispersal vary with ecological contexts.     

Internally controlled real-time PCR method for quantitative species-specific detection and vapA genotyping of Rhodococcus equi

We developed a novel quantitative real-time PCR (Q-PCR) method for the soil actinomycete Rhodococcus equi, an important horse pathogen and emerging human pathogen. Species-specific quantification was achieved by targeting the chromosomal monocopy gene choE, universally conserved in R. equi. The choE Q-PCR included an internal amplification control (IAC) for identification of false negatives. A second Q-PCR targeted the virulence plasmid gene vapA, carried by most horse isolates but infrequently found in isolates from other sources. The choE-IAC and vapA assays were 100% sensitive and specific as determined using 178 R. equi isolates, 77 nontarget bacteria, and a panel of 60 R. equi isolates with known vapA+ and vapA-negative (including vapB+) plasmid genotypes. The vapA+ frequency among isolate types was as follows: horse, 85%; human, 20%; bovine and pig, 0%; others, 27%. The choE-IAC Q-PCR could detect up to one genome equivalent using R. equi DNA or 100 bacteria/ml using DNA extracted from artificially contaminated horse bronchoalveolar lavage (BAL) fluid. Quantification was linear over a 6-log dynamic range down to approximately 10 target molecules (or 1,000 CFU/ml BAL fluid) with PCR efficiency E of >0.94. The vapA assay had similar performance but appeared unsuitable for accurate (vapA+) R. equi quantification due to variability in target gene or plasmid copy number (1 to 9). The dual-reaction Q-PCR system here reported offers a useful tool to both medical and veterinary diagnostic laboratories for the quantitative detection of R. equi and (optional) vapA+ "horse-pathogenic" genotype determination.