Depression, suicidal ideation, and associated factors: a cross-sectional study in rural Haiti

BACKGROUND: Since the 2010 earthquake in Haiti, there has been increased international attention to mental health needs throughout the country. The present study represents one of the first epidemiologic studies of depression symptomatology, suicidal ideation, and associated factors in Haiti’s Central Plateau. METHODS: We conducted a cross-sectional, zone-stratified household survey of 408 adults in Haiti’s Central Plateau. Depression symptomatology was assessed with a culturally-adapted Kreyòl version of the Beck Depression Inventory (BDI). Multivariable linear and logistic regression models were built using backward elimination, with the outcomes being continuous BDI scores and endorsing suicidal ideation, respectively. RESULTS: The mean BDI score was 20.4 (95% confidence interval [CI]: 19.3-21.5), and 6.13% (N = 25) of participants endorsed current suicidal ideation. Factors associated with BDI scores were: continuous age (adjusted beta [aβ]: 0.14, CI: 0.06-0.22), female gender (aβ: 2.1, CI: 0.18-4.0), suicidal ideation (aβ: 11.1, CI: 7.3-14.9), death in family (aβ: 2.7, CI: 0.57-4.9), and prior life-threatening illness (aβ: 2.6, CI: 0.77-4.5). Education was a risk factor for depression among women but not among men, and employment was a risk factor for both genders. Factors associated with endorsing suicidal ideation were: BDI score (ten point change) (adjusted odds ratio [aOR]: 2.5, CI: 1.7-3.6), lack of care if sick (aOR: 5.5, CI: 1.1-28.6), alcohol use (aOR: 3.3, CI: 1.3-8.2), and ever having been to a Vodou priest (aOR: 3.2, CI: 1.1-9.5). CONCLUSIONS: A large proportion of Haiti’s Central Plateau may be experiencing high levels of depression symptomatology and/or current suicidal ideation. Screening could be conducted in biomedical, religious, and Vodou healing contexts. For prevention, poverty reduction and improved healthcare access are key elements. For treatment, general psychiatric services, psychosocial services for the medically ill and their families, and substance abuse interventions should be explored. Paradoxical associations related to education and employment require further exploration

Dopamine-Induced Conformational Changes in Alpha-Synuclein

Background: Oligomerization and aggregation of α-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson's disease [1]. However, α-synuclein oligomerization and aggregation have mostly been detected indirectly in cells using detergent extraction methods [2], [3], [4]. A number of in vitro studies showed that dopamine can modulate the aggregation of α-synuclein by inhibiting the formation of or by disaggregating amyloid fibrils [5], [6], [7]. Methodology/Principal Findings: Here, we show that α-synuclein adopts a variety of conformations in primary neuronal cultures using fluorescence lifetime imaging microscopy (FLIM). Importantly, we found that dopamine, but not dopamine agonists, induced conformational changes in α-synuclein which could be prevented by blocking dopamine transport into the cell. Dopamine also induced conformational changes in α-synuclein expressed in neuronal cell lines, and these changes were also associated with alterations in oligomeric/aggregated species. Conclusion/Significance: Our results show, for the first time, a direct effect of dopamine on the conformation of α-synuclein in neurons, which may help explain the increased vulnerability of dopaminergic neurons in Parkinson's disease

The impact of non-equilibrium flow on the structure of turbulence over river dunes

This piece of research expands our description of how rivers flow over dunes on a river bed. Most of the scientific communities' research to date has used unnaturally steady conditions to measure how water moves over dunes. Yet these flow conditions are not strictly true to the variety of conditions nature produces, most importantly during floods. This research is the first detailed description of a wide range of flow states over dunes, and changes our present understanding of the structure of flow over dunes in rivers. Consequently, the scientific community will be able to use this new information to better model and simulate how rivers work, how they flood, and how they transport sediment towards the worlds deltas

A Bioelectrochemical Approach to Characterize Extracellular Electron Transfer by Synechocystis sp. PCC6803

Biophotovoltaic devices employ photosynthetic organisms at the anode of a microbial fuel cell to generate electrical power. Although a range of cyanobacteria and algae have been shown to generate photocurrent in devices of a multitude of architectures, mechanistic understanding of extracellular electron transfer by phototrophs remains minimal. Here we describe a mediatorless bioelectrochemical device to measure the electrogenic output of a planktonically grown cyanobacterium, Synechocystis sp. PCC6803. Light dependent production of current is measured, and its magnitude is shown to scale with microbial cell concentration and light intensity. Bioelectrochemical characterization of a Synechocystis mutant lacking Photosystem II demonstrates conclusively that production of the majority of photocurrent requires a functional water splitting aparatus and electrons are likely ultimately derived from water. This shows the potential of the device to rapidly and quantitatively characterize photocurrent production by genetically modified strains, an approach that can be used in future studies to delineate the mechanisms of cyanobacterial extracellular electron transport

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species

Decelerating Spread of West Nile Virus by Percolation in a Heterogeneous Urban Landscape

Vector-borne diseases are emerging and re-emerging in urban environments throughout the world, presenting an increasing challenge to human health and a major obstacle to development. Currently, more than half of the global population is concentrated in urban environments, which are highly heterogeneous in the extent, degree, and distribution of environmental modifications. Because the prevalence of vector-borne pathogens is so closely coupled to the ecologies of vector and host species, this heterogeneity has the potential to significantly alter the dynamical systems through which pathogens propagate, and also thereby affect the epidemiological patterns of disease at multiple spatial scales. One such pattern is the speed of spread. Whereas standard models hold that pathogens spread as waves with constant or increasing speed, we hypothesized that heterogeneity in urban environments would cause decelerating travelling waves in incipient epidemics. To test this hypothesis, we analysed data on the spread of West Nile virus (WNV) in New York City (NYC), the 1999 epicentre of the North American pandemic, during annual epizootics from 2000–2008. These data show evidence of deceleration in all years studied, consistent with our hypothesis. To further explain these patterns, we developed a spatial model for vector-borne disease transmission in a heterogeneous environment. An emergent property of this model is that deceleration occurs only in the vicinity of a critical point. Geostatistical analysis suggests that NYC may be on the edge of this criticality. Together, these analyses provide the first evidence for the endogenous generation of decelerating travelling waves in an emerging infectious disease. Since the reported deceleration results from the heterogeneity of the environment through which the pathogen percolates, our findings suggest that targeting control at key sites could efficiently prevent pathogen spread to remote susceptible areas or even halt epidemics

Drivers of reef shark abundance and biomass in the Solomon Islands

Remote island nations face a number of challenges in addressing concerns about shark population status, including access to rigorously collected data and resources to manage fisheries. At present, very little data are available on shark populations in the Solomon Islands and scientific surveys to document shark and ray diversity and distribution have not been completed. We aimed to provide a baseline of the relative abundance and diversity of reef sharks and rays and assess the major drivers of reef shark abundance/biomass in the Western Province of the Solomon Islands using stereo baited remote underwater video. On average reef sharks were more abundant than in surrounding countries such as Fiji and Indonesia, yet below that of remote islands without historical fishing pressure, suggesting populations are relatively healthy but not pristine. We also assessed the influence of location, habitat type/complexity, depth and prey biomass on reef shark abundance and biomass. Location was the most important factor driving reef shark abundance and biomass with two times the abundance and a 43% greater biomass of reef sharks in the more remote locations, suggesting fishing may be impacting sharks in some areas. Our results give a much needed baseline and suggest that reef shark populations are still relatively unexploited, providing an opportunity for improved management of sharks and rays in the Solomon Islands

The contribution of X-linked coding variation to severe developmental disorders

Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders