Geopolitical determinants of mental health and global health inequities

Geopolitical determinants of health have been well recognized by the World Health Organization and are increasingly being discussed across governments, institutions, academics, policy makers, and across global health sector. Geopolitical determinants of health are events, structures, processes, and factors that influence individual health including mental health, public and population mental health both directly and indirectly. Consequently, nation’s responses to these factors will affect short-term and long-term health outcomes. Geopolitical factors are becoming increasingly more important as they influence directly and indirectly social determinants of health. These factors clearly impact both physical and mental health leading to health inequities and inequalities. It is important to factor in geopolitical determinants in resource allocation and funding as well as policy making as has been highlighted by the recent pandemic and variable access to vaccines. Geopolitical determinants would be integral when addressing all global health inequities. These play a major role in resource allocation, policy and planning to meet today’s global health challenges

Multiple spatial behaviours govern social network positions in a wild ungulate

The structure of wild animal social systems depends on a complex combination of intrinsic and extrinsic drivers. Population structuring and spatial behaviour are key determinants of individuals’ observed social behaviour, but quantifying these spatial components alongside multiple other drivers remains difficult due to data scarcity and analytical complexity. We used a 43‐year dataset detailing a wild red deer population to investigate how individuals’ spatial behaviours drive social network positioning, while simultaneously assessing other potential contributing factors. Using Integrated Nested Laplace Approximation (INLA) multi‐matrix animal models, we demonstrate that social network positions are shaped by two‐dimensional landscape locations, pairwise space sharing, individual range size, and spatial and temporal variation in population density, alongside smaller but detectable impacts of a selection of individual‐level phenotypic traits. These results indicate strong, multifaceted spatiotemporal structuring in this society, emphasising the importance of considering multiple spatial components when investigating the causes and consequences of sociality

Using Population Mixtures to Optimize the Utility of Genomic Databases: Linkage Disequilibrium and Association Study Design in India

When performing association studies in populations that have not been the focus of large-scale investigations of haplotype variation, it is often helpful to rely on genomic databases in other populations for study design and analysis – such as in the selection of tag SNPs and in the imputation of missing genotypes. One way of improving the use of these databases is to rely on a mixture of database samples that is similar to the population of interest, rather than using the single most similar database sample. We demonstrate the effectiveness of the mixture approach in the application of African, European, and East Asian HapMap samples for tag SNP selection in populations from India, a genetically intermediate region underrepresented in genomic studies of haplotype variation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65949/1/j.1469-1809.2008.00457.x.pd

The crafting of an (un)enterprising community: context and the social practice of talk

YesThis article examines a ‘deprived’ UK community to identify how (dis)connections between context and enterprise are produced within accounts of a particular locality. We used a discursive psychological approach to examine how the community depicted itself as a context for enterprise. Our analysis identified three discursive repertoires mobilised by a range of voices in the community which combined to portray an unenterprising community and create a conceptual deadlock for enterprise. We suggest it is too deterministic to assume context is fixed and controls the potential for entrepreneurial development. Instead, we should consider social practices, including talk, that help construct the contexts in which entrepreneurship is expected to occur.The research resorted in this article was funded by an Economic and Social Research Council studentship

Urocortin 2 Infusion in Healthy Humans Hemodynamic, Neurohormonal, and Renal Responses

ObjectivesWe sought to examine the effects of urocortin (UCN) 2 infusion on hemodynamic status, cardiovascular hormones, and renal function in healthy humans.BackgroundUrocortin 2 is a vasoactive and cardioprotective peptide belonging to the corticotrophin-releasing factor peptide family. Recent reports indicate the urocortins exert important effects beyond the hypothalamo-pituitary-adrenal axis upon cardiovascular and vasohumoral function in health and cardiac disease.MethodsWe studied 8 healthy unmedicated men on 3 separate occasions 2 to 5 weeks apart. Subjects received placebo, 25-μg low-dose (LD), and 100-μg high-dose (HD) of UCN 2 intravenously over the course of 1 h in a single-blind, placebo-controlled, dose-escalation design. Noninvasive hemodynamic indexes, neurohormones, and renal function were measured.ResultsThe administration of UCN 2 dose-dependently increased cardiac output (mean peak increments ± SEM) (placebo 0.5 ± 0.2 l/min; LD 2.1 ± 0.6 l/min; HD 5.0 ± 0.8 l/min; p < 0.001), heart rate (placebo 3.3 ± 1.0 beats/min; LD 8.8 ± 1.8 beats/min; HD 17.8 ± 2.1 beats/min; p < 0.001), and left ventricular ejection fraction (placebo 0.6 ± 1.4%; LD 6.6 ± 1.5%; HD 14.1 ± 0.8%; p < 0.001) while decreasing systemic vascular resistance (placebo −128 ± 50 dynes·s/cm5; LD −407 ± 49 dynes·s/cm5; HD −774 ± 133 dynes·s/cm5; p < 0.001). Activation of plasma renin activity (p = 0.002), angiotensin II (p = 0.001), and norepinephrine (p < 0.001) occurred only with the higher 100-μg dose. Subtle decreases in urine volume (p = 0.012) and natriuresis (p = 0.001) were observed.ConclusionsBrief intravenous infusions of UCN 2 in healthy humans induced pronounced dose-related increases in cardiac output, heart rate, and left ventricular ejection fraction while decreasing systemic vascular resistance. Subtle renal effects and activation of plasma renin, angiotensin II, and norepinephrine (at high-dose only) were observed. These findings warrant further investigation of the role of UCN 2 in circulatory regulation and its potential therapeutic application in heart disease

Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

Background: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.&lt;p&gt;&lt;/p&gt; Methods: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.&lt;p&gt;&lt;/p&gt; Results: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.&lt;p&gt;&lt;/p&gt; Conclusions: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.&lt;p&gt;&lt;/p&gt

Effect of Exercise Training and +Gz Acceleration Training on Men

Countermeasures for reduction in work capacity (maximal oxygen uptake and strength) during spaceflight and enhanced orthostatic intolerance during re-entry, landing and egress from the return vehicle are continuing problems. The purpose for this study was to test the hypothesis that passive-acceleration training; supine, interval, exercise plus acceleration training and exercise combined with acceleration training would improve orthostatic tolerance in ambulatory men; and that addition of the aerobic exercise conditioning would not alter this improved tolerance from that of passive-acceleration training. Seven men (24-38 yr) underwent "Passive" training on the Ames human-powered centrifuge (HPC) for 30 min, "Exercise" training on the cycle ergometer with constant +Gz acceleration; and "Combined" exercise training at 40% to 90% of the HPC +Gz(max) exercise level. Maximal supine exercise loads increased significant (P<0.05) by 8.3% (Passive), 12.6% (Exercise), and by 15.4% (Combined) after training, but their post-training maximal oxygen uptakes and maximal heart rates were unchanged. Maximal time to fatigue (endurance) was unchanged with Passive was increased (P<0.05) with Exercise and Combined training. Thus, the exercise in the Exercise and Combined training Phases resulted in greater maximal loads and endurance without effect on maximal oxygen uptake or heart rate. There was a 4% to 6% increase (P<0.05) in all four quadriceps muscle volumes (right and left) after post-Combined training. Resting pre-tilt heart rate was elevated by 12.9% (P<0.05) only after Passive training suggesting that the exercise training attenuated the HR response. Plasma volume (% Delta) was uniformly decreased by 8% to 14% (P<0.05) at tilt-tolerance pre- vs. post-training indicating essentially no effect of training on the level of hypovolemia. Post-training tilt-tolerance time and heart rate were increased (P<0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training appeared to attenuate the increased Passive tilt-tolerance