Association of socio-economic position and suicide/attempted suicide in low and middle income countries in South and South-East Asia - a systematic review

BACKGROUND: Forty percent of the world’s suicide deaths occur in low and middle income countries (LAMIC) in Asia. There is a recognition that social factors, such as socioeconomic position (SEP), play an important role in determining suicidal risk in high income countries, but less is known about the association in LAMIC. METHODS: The objective of this systematic review was to synthesise existing evidence of the association between SEP and attempted suicide/suicide risk in LAMIC countries in South and South East Asia. Web of Science, MEDLINE, MEDLINE in Process, EMBASE, PsycINFO, and article reference lists/forward citations were searched for eligible studies. Epidemiological studies reporting on the association of individual SEP with suicide and attempted suicide were included. Study quality was assessed using an adapted rating tool and a narrative synthesis was conducted. RESULTS: Thirty-one studies from nine countries were identified; 31 different measures of SEP were reported, with education being the most frequently recorded. Most studies suggest that lower levels of SEP are associated with an increased risk of suicide/attempted suicide, though findings are not always consistent between and within countries. Over half of the studies included in this review were of moderate/low quality. The SEP risk factors with the most consistent association across studies were asset based measures (e.g. composite measures); education; measures of financial difficulty and subjective measures of financial circumstance. Several studies show a greater than threefold increased risk in lower SEP groups with the largest and most consistent association with subjective measures of financial circumstance. CONCLUSION: The current evidence suggests that lower SEP increases the likelihood of suicide/attempted suicide in LAMIC in South and South East Asia. However, the findings are severely limited by study quality; larger better quality studies are therefore needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2014:CRD42014006521 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-2301-5) contains supplementary material, which is available to authorized users

Risk of neuropsychiatric adverse events associated with varenicline:systematic review and meta-analysis

Objective To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in randomised controlled trials. Design Systematic review and meta-analysis comparing study effects using two summary estimates in fixed effects models, risk differences, and Peto odds ratios. Data sources Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov. Eligibility criteria for selecting studies Randomised controlled trials with a placebo comparison group that reported on neuropsychiatric adverse events (depression, suicidal ideation, suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence, fatigue, anxiety) and death. Studies that did not involve human participants, did not use the maximum recommended dose of varenicline (1 mg twice daily), and were cross over trials were excluded. Results In the 39 randomised controlled trials (10 761 participants), there was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other). Conclusions This meta-analysis found no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline. These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline. There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams. These side effects, however,are already well recognised. Systematic review registration PROSPERO 2014:CRD42014009224

Temperature-Dependence of Weibel-Palade Body Exocytosis and Cell Surface Dispersal of von Willebrand Factor and Its Propolypeptide

Background: Weibel-Palade bodies (WPB) are endothelial cell (EC) specific secretory organelles containing Von Willebrand factor (VWF). The temperature-dependence of Ca2+-driven WPB exocytosis is not known, although indirect evidence suggests that WPB exocytosis may occur at very low temperatures. Here we quantitatively analyse the temperature-dependence of Ca2+-driven WPB exocytosis and release of secreted VWF from the cell surface of ECs using fluorescence microscopy of cultured human ECs containing fluorescent WPBs. Principal Findings: Ca2+-driven WPB exocytosis occurred at all temperatures studied (7–37°C). The kinetics and extent of WPB exocytosis were strongly temperature-dependent: Delays in exocytosis increased from 0.92 s at 37°C to 134.2 s at 7°C, the maximum rate of WPB fusion decreased from 10.0±2.2 s−1 (37°C) to 0.80±0.14 s−1 (7°C) and the fractional extent of degranulation of WPBs in each cell from 67±3% (37°C) to 3.6±1.3% (7°C). A discrepancy was found between the reduction in Ca2+-driven VWF secretion and WPB exocytosis at reduced temperature; at 17°C VWF secretion was reduced by 95% but WPB exocytosis by 75–80%. This discrepancy arises because VWF dispersal from sites of WPB exocytosis is largely prevented at low temperature. In contrast VWF-propolypeptide (proregion) dispersal from WPBs, although slowed, was complete within 60–120 s. Novel antibodies to the cleaved and processed proregion were characterised and used to show that secreted proregion more accurately reports the secretion of WPBs at sub-physiological temperatures than assay of VWF itself. Conclusions : We report the first quantitative analysis of the temperature-dependence of WPB exocytosis. We provide evidence; by comparison of biochemical data for VWF or proregion secretion with direct analysis of WPB exocytosis at reduced temperature, that proregion is a more reliable marker for WPB exocytosis at reduced temperature, where VWF-EC adhesion is increased

Probiotics and competitive exclusion of pathogens in shrimp aquaculture

This is the final version. Available from the publisher via the DOI in this record.Probiotics, live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, offer an alternative to antibiotics and have become popular among shrimp farmers for use in the regulation of pond water quality, promotion of shrimp growth and the prevention of disease. Most shrimp probiotics are selected for testing based on their ability to competitively exclude pathogens through bacterial antagonism assays, although the mechanisms of pathogen exclusion are rarely investigated. In this review, we provide a comprehensive overview of the mechanisms of competitive exclusion (interference and exploitation competition) by species screened and subsequently identified as shrimp probiotics based on their ability to inhibit the growth of pathogenic bacteria in vitro. We show that the current methods used to identify potential probiotics preferentially select for interference-based competitive mechanisms and may overlook the potential of many species to be considered a probiotic. Furthermore, we show that the efficiency of a probiotic in vivo may be improved by considering the suitability of competitive strategies to shrimp farming conditions. We highlight important limitations and future directions for the screening and identification of probiotics in shrimp aquaculture, to aid in the development of effective and sustainable microbial management strategies.Biotechnology and Biological Sciences Research Council (BBSRC

HIV Integrase Inhibitors Block Replication of Alpha-, Beta-, and Gammaherpesviruses

ABSTRACT The catalytic site of the HIV integrase is contained within an RNase H-like fold, and numerous drugs have been developed that bind to this site and inhibit its activity. Herpes simplex virus (HSV) encodes two proteins with potential RNase H-like folds, the infected cell protein 8 (ICP8) DNA-binding protein, which is necessary for viral DNA replication and exhibits recombinase activity in vitro, and the viral terminase, which is essential for viral DNA cleavage and packaging. Therefore, we hypothesized that HIV integrase inhibitors might also inhibit HSV replication by targeting ICP8 and/or the terminase. To test this, we evaluated the effect of 118-D-24, a potent HIV integrase inhibitor, on HSV replication. We found that 118-D-24 inhibited HSV-1 replication in cell culture at submillimolar concentrations. To identify more potent inhibitors of HSV replication, we screened a panel of integrase inhibitors, and one compound with greater anti-HSV-1 activity, XZ45, was chosen for further analysis. XZ45 significantly inhibited HSV-1 and HSV-2 replication in different cell types, with 50% inhibitory concentrations that were approximately 1 µM, but exhibited low cytotoxicity, with a 50% cytotoxic concentration greater than 500 µM. XZ45 blocked HSV viral DNA replication and late gene expression. XZ45 also inhibited viral recombination in infected cells and ICP8 recombinase activity in vitro. Furthermore, XZ45 inhibited human cytomegalovirus replication and induction of Kaposi’s sarcoma herpesvirus from latent infection. Our results argue that inhibitors of enzymes with RNase H-like folds may represent a general antiviral strategy, which is useful not only against HIV but also against herpesviruses

Using molecular and crowd‐sourcing methods to assess breeding ground diet of a migratory brood parasite of conservation concern

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThe research data supporting this publication are openly available from Dryad at https://doi.org/10.5061/dryad.v6wwpzgsp and from NCBI Sequence Read Archive under BioProject number PRJNA606798Breeding ground food availability is critical to the survival and productivity of adult birds. The common cuckoo Cuculus canorus is a brood‐parasitic Afro‐Palearctic migrant bird exhibiting long‐term (breeding) population declines in many European countries. Variation in population trend between regions and habitats suggests breeding ground drivers such as adult food supply. However, cuckoo diet has not been studied in detail since before the most significant population declines in Europe began in the mid‐1980s. 20th century studies of cuckoo diet largely comprised field observations likely to carry bias towards larger prey taxa. Here we demonstrate the potential value of 1) using high‐throughput DNA sequencing of invertebrate prey in faeces to determine cuckoo diet with minimal bias towards large prey taxa, and 2) using crowd‐sourced digital photographs from across Britain to identify lepidopteran cuckoo prey taxa during recent years post‐decline (2005‐2016). DNA analysis found a high frequency of Lepidoptera, including moths of family Lasiocampidae, prominent within the past literature, but also grasshoppers (Orthoptera) and flies (Diptera) that may be overlooked by field observation methodologies. The range of larval lepidopteran prey identified from photographs largely agreed with those previously documented, with potential signs of reduced diversity, and identities of key adult prey taxa were supported by molecular results. Notably, many identified cuckoo prey taxa have shown severe declines due to agricultural intensification, suggesting this has driven spatial patterns of cuckoo loss. Landscape‐scale, lowland rewilding interventions provide opportunities to understand the scale of reversal of previous agricultural intensification that may be necessary to restore prey populations sufficiently to permit recolonization by cuckoos.Dartmoor National Park AuthorityNatural Environment Research Council (NERC)University of ExeterRoyal Society for the Protection of Birds (RSPB

Vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms

Current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. We developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. By engineering the vesicular stomatitis virus (VSV) to encode a fluorophore and either the rabies virus glycoprotein (RABV-G) or its own glycoprotein (VSV-G), we created viruses that can transsynaptically label neuronal circuits in either the retrograde or anterograde direction, respectively. The vectors were investigated for their utility as polysynaptic tracers of chicken and zebrafish visual pathways. They showed patterns of connectivity consistent with previously characterized visual system connections, and revealed several potentially novel connections. Further, these vectors were shown to infect neurons in several other vertebrates, including Old and New World monkeys, seahorses, axolotls, and Xenopus. They were also shown to infect two invertebrates, Drosophila melanogaster, and the box jellyfish, Tripedalia cystophora, a species previously intractable for gene transfer, although no clear evidence of transsynaptic spread was observed in these species. These vectors provide a starting point for transsynaptic tracing in most vertebrates, and are also excellent candidates for gene transfer in organisms that have been refractory to other methods

Astrometric and Light-travel Time Orbits to Detect Low-mass Companions: A Case Study of the Eclipsing System R Canis Majoris

We discuss a method to determine orbital properties and masses of low-mass bodies orbiting eclipsing binaries. The analysis combines long-term eclipse timing modulations (light-travel time or LTT effect) with short-term, high-accuracy astrometry. As an illustration of the method, the results of a comprehensive study of Hipparcos astrometry and over a hundred years of eclipse timings of the Algol-type eclipsing binary R Canis Majoris are presented. A simultaneous solution of the astrometry and the LTTs yields an orbital period of P_12=92.8+/-1.3 yr, an LTT semiamplitude of 2574+/-57 s, an angular semi-major axis of a_12=117+/-5 mas, and values of the orbital eccentricity and inclination of e_12=0.49+/-0.05, and i_12=91.7+/-4.7 deg, respectively. Adopting the total mass of R CMa of M_12=1.24+/-0.05 Mo, the mass of the third body is M_3=0.34+/-0.02 Mo and the semi-major axis of its orbit is a_3=18.7+/-1.7 AU. From its mass, the third body is either a dM3-4 star or, more unlikely, a white dwarf. With the upcoming microarcsecond-level astrometric missions, the technique that we discuss can be successfully applied to detect and characterize long-period planetary-size objects and brown dwarfs around eclipsing binaries. Possibilities for extending the method to pulsating variables or stars with transiting planets are briefly addressed.Comment: 9 pages, 3 figures, accepted for publication in AJ (April 2002 issue

Establishment of an AAV Reverse Infection-Based Array

Background: The development of a convenient high-throughput gene transduction approach is critical for biological screening. Adeno-associated virus (AAV) vectors are broadly used in gene therapy studies, yet their applications in in vitro high-throughput gene transduction are limited. Principal Findings: We established an AAV reverse infection (RI)-based method in which cells were transduced by quantified recombinant AAVs (rAAVs) pre-coated onto 96-well plates. The number of pre-coated rAAV particles and number of cells loaded per well, as well as the temperature stability of the rAAVs on the plates, were evaluated. As the first application of this method, six serotypes or hybrid serotypes of rAAVs (AAV1, AAV2, AAV5/5, AAV8, AAV25 m, AAV28 m) were compared for their transduction efficiencies using various cell lines, including BHK21, HEK293, BEAS-2BS, HeLaS3, Huh7, Hepa1-6, and A549. AAV2 and AAV1 displayed high transduction efficiency; thus, they were deemed to be suitable candidate vectors for the RI-based array. We next evaluated the impact of sodium butyrate (NaB) treatment on rAAV vectormediated reporter gene expression and found it was significantly enhanced, suggesting that our system reflected the biological response of target cells to specific treatments. Conclusions/Significance: Our study provides a novel method for establishing a highly efficient gene transduction arra