Neighborhood Stressors and Race/Ethnic Differences in Hypertension Prevalence (The Multi-Ethnic Study of Atherosclerosis)

Background: The reasons for racial/ethnic disparities in hypertension (HTN) prevalence in the United States are poorly understood.Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether individual- and neighborhood-level chronic stressors contribute to these disparities in cross-sectional analyses. The sample consisted of 2,679 MESA participants (45-84 years) residing in Baltimore, New York, and North Carolina. HTN was defined as systolic or diastolic blood pressure ≥140 or 90 mm Hg, or taking antihypertensive medications. Individual-level chronic stress was measured by self-reported chronic burden and perceived major and everyday discrimination. A measure of neighborhood (census tract) chronic stressors (i.e., physical disorder, violence) was developed using data from a telephone survey conducted with other residents of MESA neighborhoods. Binomial regression was used to estimate associations between HTN and race/ethnicity before and after adjustment for individual and neighborhood stressors.Results: The prevalence of HTN was 59.5% in African Americans (AAs), 43.9% in Hispanics, and 42.0% in whites. Age- and sex-adjusted relative prevalences of HTN (compared to whites) were 1.30 (95% confidence interval (CI): 1.22-1.38) for AA and 1.16 (95% CI: 1.04-1.31) for Hispanics. Adjustment for neighborhood stressors reduced these to 1.17 (95% CI: 1.11-1.22) and 1.09 (95% CI: 1.00-1.18), respectively. Additional adjustment for individual-level stressors, acculturation, income, education, and other neighborhood features only slightly reduced these associations.Conclusion: Neighborhood chronic stressors may contribute to race/ethnic differences in HTN prevalence in the United States.American Journal of Hypertension (2010).http://deepblue.lib.umich.edu/bitstream/2027.42/78329/1/MujahidDiezRoux2010_AmJHTN.pd

Mood instability, mental illness and suicidal ideas : results from a household survey

Purpose: There is weak and inconsistent evidence that mood instability (MI) is associated with depression, post traumatic stress disorder (PTSD) and suicidality although the basis of this is unclear. Our objectives were first to test whether there is an association between depression and PTSD, and MI and secondly whether MI exerts an independent effect on suicidal thinking over and above that explained by common mental disorders. Methods: We used data from the Adult Psychiatric Morbidity Survey 2007 (N = 7,131). Chi-square tests were used to examine associations between depression and PTSD, and MI, followed by regression modelling to examine associations between MI and depression, and with PTSD. Multiple logistic regression analyses were used to assess the independent effect of MI on suicidal thinking, after adjustment for demographic factors and the effects of common mental disorder diagnoses. Results: There are high rates of MI in depression and PTSD and the presence of MI increases the odds of depression by 10.66 [95 % confidence interval (CI) 7.51–15.13] and PTSD by 8.69 (95 % CI 5.90–12.79), respectively, after adjusting for other factors. Mood instability independently explained suicidal thinking, multiplying the odds by nearly five (odds ratio 4.82; 95 % CI 3.39–6.85), and was individually by some way the most important single factor in explaining suicidal thoughts. Conclusions: MI is strongly associated with depression and PTSD. In people with common mental disorders MI is clinically significant as it acts as an additional factor exacerbating the risk of suicidal thinking. It is important to enquire about MI as part of clinical assessment and treatment studies are required

Adapting HIV prevention evidence-based interventions in practice settings: an interview study

<p>Abstract</p> <p>Background</p> <p>Evidence-based interventions that are being delivered in real-world settings are adapted to enhance the external validity of these interventions. The purpose of this study was to examine multiple intervention adaptations made during pre-implementation, implementation, maintenance, and evolution phases of human immunodeficiency virus HIV prevention technology transfer. We examined two important categories of adaptations -- modifications to key characteristics, such as activities or delivery methods of interventions and reinvention of the interventions including addition and deletion of core elements.</p> <p>Methods</p> <p>Study participants were thirty-four community-based organization staff who were implementing evidence-based interventions in Los Angeles, California. Participants were interviewed twice and interviews were professionally transcribed. Transcriptions were coded by two coders with good inter-rater reliability (kappa coefficient = 0.73). Sixty-two open-ended codes for adaptation activities, which were linked to 229 transcript segments, were categorized as modifications of key characteristics or reinvention.</p> <p>Results</p> <p>Participants described activities considered modifications to key characteristics and reinvention of evidence-based interventions during pre-implementation, implementation, and maintenance phases. None of the participants reported accessing technical assistance or guidance when reinventing their interventions. Staff executed many of the recommended steps for sound adaptation of these interventions for new populations and settings.</p> <p>Conclusion</p> <p>Staff reported modifying and reinventing interventions when translating HIV prevention programs into practice. Targeted technical assistance for formative evaluation should be focused on the pre-implementation phase during which frequent modifications occur. Continuous or repeated measurements of fidelity are recommended. Increased technical assistance and guidance are needed to ensure that reinventions are evaluated and consistent with the aims of the original interventions. Providing strategic technical assistance and written guidance can facilitate effective HIV prevention technology transfer of evidence-based interventions.</p

The what and where of adding channel noise to the Hodgkin-Huxley equations

One of the most celebrated successes in computational biology is the Hodgkin-Huxley framework for modeling electrically active cells. This framework, expressed through a set of differential equations, synthesizes the impact of ionic currents on a cell's voltage -- and the highly nonlinear impact of that voltage back on the currents themselves -- into the rapid push and pull of the action potential. Latter studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional) description than the original Hodgkin-Huxley equations. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic Hodgkin-Huxley equations. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly Matlab simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950) and http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl

The Cytosolic Tail of the Golgi Apyrase Ynd1 Mediates E4orf4-Induced Toxicity in Saccharomyces cerevisiae

The adenovirus E4 open reading frame 4 (E4orf4) protein contributes to regulation of the progression of virus infection. When expressed individually, E4orf4 was shown to induce non-classical transformed cell-specific apoptosis in mammalian cells. At least some of the mechanisms underlying E4orf4-induced toxicity are conserved from yeast to mammals, including the requirement for an interaction of E4orf4 with protein phosphatase 2A (PP2A). A genetic screen in yeast revealed that the Golgi apyrase Ynd1 associates with E4orf4 and contributes to E4orf4-induced toxicity, independently of Ynd1 apyrase activity. Ynd1 and PP2A were shown to contribute additively to E4orf4-induced toxicity in yeast, and to interact genetically and physically. A mammalian orthologue of Ynd1 was shown to bind E4orf4 in mammalian cells, confirming the evolutionary conservation of this interaction. Here, we use mutation analysis to identify the cytosolic tail of Ynd1 as the protein domain required for mediation of the E4orf4 toxic signal and for the interaction with E4orf4. We also show that E4orf4 associates with cellular membranes in yeast and is localized at their cytoplasmic face. However, E4orf4 is membrane-associated even in the absence of Ynd1, suggesting that additional membrane proteins may mediate E4orf4 localization. Based on our results and on a previous report describing a collection of Ynd1 protein partners, we propose that the Ynd1 cytoplasmic tail acts as a scaffold, interacting with a multi-protein complex, whose targeting by E4orf4 leads to cell death

The relationship between childhood body weight and dental caries experience:an umbrella systematic review protocol

Abstract Background Obesity and dental caries are global public health problems which can impact in childhood and throughout the life course. In simple terms, childhood dental caries and body weight are linked via the common risk factor of diet. An association between dental caries and obesity has been described in a number of studies and reviews. However, similarly, a relationship has also been noted between low body weight and caries experience in children. This protocol will provide the framework for an umbrella review to address the following question: Does the available evidence support a relationship between dental caries experience and body weight in the child population? Methods This review protocol outlines the process to carry out an umbrella systematic review which will synthesise previous reviews of childhood dental caries experience and body weight. An umbrella review methodology will be used to examine the methodological and reporting quality of existing reviews. Discussion The final umbrella review aims to aggregate the available evidence in order to provide a summary for policymakers and to inform healthcare interventions. Systematic review registration PROSPERO CRD4201604730

Transient disruption of M1 during response planning impairs subsequent offline consolidation

Transcranial magnetic stimulation (TMS) was used to probe the involvement of the left primary motor cortex (M1) in the consolidation of a sequencing skill. In particular we asked: (1) if M1 is involved in consolidation of planning processes prior to response execution (2) whether movement preparation and movement execution can undergo consolidation independently and (3) whether sequence consolidation can occur in a stimulus specific manner. TMS was applied to left M1 while subjects prepared left hand sequential finger responses for three different movement sequences, presented in an interleaved fashion. Subjects also trained on three control sequences, where no TMS was applied. Disruption of subsequent consolidation was observed, but only for sequences where subjects had been exposed to TMS during training. Further, reduced consolidation was only observed for movement preparation, not movement execution. We conclude that left M1 is causally involved in the consolidation of effective response planning for left hand movements prior to response execution, and mediates consolidation in a sequence specific manner. These results provide important new insights into the role of M1 in sequential memory consolidation and sequence response planning