Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders

Major depressive and bipolar disorders predispose to atherosclerosis, and there is accruing data from animal model, epidemiological, and genomic studies that commonly used antihypertensive drugs may have a role in the pathogenesis or course of mood disorders. In this study, we propose to determine whether antihypertensive drugs have an impact on mood disorders through the analysis of patients on monotherapy with different classes of antihypertensive drugs from a large hospital database of 525 046 patients with follow-up for 5 years. There were 144 066 eligible patients fulfilling the inclusion criteria: age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days. The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641 685 person-years of follow-up). Patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had the lowest risk for mood disorder admissions, and compared with this group, those on β-blockers (hazard ratio=2.11; [95% confidence interval, 1.12–3.98]; P=0.02) and calcium antagonists (2.28 [95% confidence interval, 1.13–4.58]; P=0.02) showed higher risk, whereas those on no antihypertensives (1.63 [95% confidence interval, 0.94–2.82]; P=0.08) and thiazide diuretics (1.56 [95% confidence interval, 0.65–3.73]; P=0.32) showed no significant difference. Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and β-blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders

Hsc70-induced changes in clathrin-auxilin cage structure suggest a role for clathrin light chains in cage disassembly

The molecular chaperone, Hsc70, together with its co-factor, auxilin, facilitates the ATP-dependent removal of clathrin during clathrin-mediated endocytosis in cells. We have used cryo-electron microscopy to determine the 3D structure of a complex of clathrin, auxilin401-910 and Hsc70 at pH 6 in the presence of ATP, frozen within 20 seconds of adding Hsc70 in order to visualize events that follow the binding of Hsc70 to clathrin and auxilin before clathrin disassembly. In this map, we observe density beneath the vertex of the cage that we attribute to bound Hsc70. This density emerges asymmetrically from the clathrin vertex, suggesting preferential binding by Hsc70 for one of the three possible sites at the vertex. Statistical comparison with a map of whole auxilin and clathrin previously published by us reveals the location of statistically significant differences which implicate involvement of clathrin light chains in structural rearrangements which occur after Hsc70 is recruited. Clathrin disassembly assays using light scattering suggest that loss of clathrin light chains reduces the efficiency with which auxilin facilitates this reaction. These data support a regulatory role for clathrin light chains in clathrin disassembly in addition to their established role in regulating clathrin assembly

Evolutionary game theory in growing populations

Existing theoretical models of evolution focus on the relative fitness advantages of different mutants in a population while the dynamic behavior of the population size is mostly left unconsidered. We here present a generic stochastic model which combines the growth dynamics of the population and its internal evolution. Our model thereby accounts for the fact that both evolutionary and growth dynamics are based on individual reproduction events and hence are highly coupled and stochastic in nature. We exemplify our approach by studying the dilemma of cooperation in growing populations and show that genuinely stochastic events can ease the dilemma by leading to a transient but robust increase in cooperationComment: 4 pages, 2 figures and 2 pages supplementary informatio

Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care. Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1). Results: At T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts. Conclusions: Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission

Laterally driven interfaces in the three-dimensional Ising lattice gas

We study the steady state of a phase-separated driven Ising lattice gas in three dimensions using computer simulations with Kawasaki dynamics. An external force field F(z) acts in the x direction parallel to the interface, creating a lateral order parameter current j^x(z) which varies with distance z from the interface. Above the roughening temperature, our data for `shear-like' linear variation of F(z) are in agreement with the picture wherein shear acts as effective confinement in this system, thus supressing the interfacial capillary-wave fluctuations. We find sharper magnetisation profiles and reduced interfacial width as compared to equilibrium. Pair correlations are more suppressed in the vorticity direction y than in the driving direction; the opposite holds for the structure factor. Lateral transport of capillary waves occurs for those forms of F(z) for which the current j^x(z) is an odd function of z, for example the shear-like drive, and a `step-like' driving field. For a V-shaped driving force no such motion occurs, but capillary waves are suppressed more strongly than for the shear-like drive. These findings are in agreement with our previous simulation studies in two dimensions. Near and below the (equilibrium) roughening temperature the effective-confinement picture ceases to work, but the lateral motion of the interface persists.Comment: 20 pages, 11 figures, submitted to Phys. Rev.

Heart rate variability during high-speed treadmill exercise and recovery in Thoroughbred racehorses presented for poor performance

Background: Heart rate variability (HRV) analysis measures the inter-beat interval variation of successive cardiac cycles. Measurement of these indices has been used to assess cardiac autonomic modulation and for arrhythmia identification in exercising horses.Objectives: To report HRV indices during submaximal exercise, strenuous exercise and recovery, and explore relationships with clinical conditions (arrhythmias, lameness, equine gastric ulcer syndrome (EGUS), lower airway inflammation and upper respiratory tract obstructions (URTO) in Thoroughbred (TB) racehorses.Study Design: Retrospective, observational cross-sectional study.Methods: One hundred and eighty Thoroughbred horses underwent a treadmill exercise test with simultaneous electrocardiographic (ECG) recording. Time-domain HRV indices (standard deviation of the R-R interval (SDRR); root mean square of successive differences (RMSSD)) were derived for submaximal and strenuous exercise and recovery segments. Clinical conditions (arrhythmia (during each phase of exercise), lameness, EGUS, lower airway inflammation and URTO) were assigned to binary categories for statistical analysis. Relationships between selected HRV indices and the clinical conditions were explored using linear regression models. Results: During submaximal exercise, lameness was associated with decreased logRMSSD (B= -0.19 95% CI -0.31 to -0.06, P= 0.006) and arrhythmia was associated with increased logRMSSD (B= 0.31 95% CI 0.01-.608, P=0.04). During strenuous exercise, arrhythmia was associated with increased HRV indices (logSDRR B= 0.51 95% CI 0.40-0.62, PMain Limitations: The main limitations of this retrospective study were that not every horse had the full range of clinical testing, therefore some horses may have had undetected abnormalities. Conclusions: The presence of arrhythmia increased HRV in both phases of exercise and recovery. Lameness decreased HRV during submaximal exercise

Fashion and passion: marketing sex to women

Against a backdrop of a ‘pornographication’ of mainstream media and the emergence of a more heavily sexualized culture, women are increasingly targeted as sexual consumers. In the UK, the success of TV shows like Sex and the City and the ‘fashion ‘n’ passion’ of sex emporia like Ann Summers suggests that late twentieth century discourses which foregrounded female pleasure have crystallised in a new form of sexual address to women. This article examines how sex products are being marketed for female consumers, focussing on the websites of sex businesses such as Myla, Babes n Horny, Beecourse, tabooboo and Ann Summers. It asks how a variety of existing discourses – of fashion, consumerism, bodily pleasure and sexuality - are drawn on in the construction of this new market, how they negotiate the dangers and pleasures of sexuality for women, and what they show about the construction of ‘new’ female sexualities.</p

Nature of socioeconomic inequalities in neonatal mortality: population based study

Objective To investigate time trends in socioeconomic inequalities in cause specific neonatal mortality in order to assess changing patterns in mortality due to different causes, particularly prematurity, and identify key areas of focus for future intervention strategies

Mechanisms underlying the exquisite sensitivity of Candida albicans to combinatorial cationic and oxidative stress that enhances the potent fungicidal activity of phagocytes

Copyright © 2014 Kaloriti et al.Peer reviewedPublisher PD

2016 Aerial Imagery Acquired to Monitor the Distribution and Abundance of Submerged Aquatic Vegetation in Chesapeake Bay and Coastal Bays

Multispectral aerial imagery acquired in 2016 to monitor the distribution and abundance of submerged aquatic vegetation in Chesapeake Bay and coastal bays