Functional Impairment of Central Memory CD4 T Cells Is a Potential Early Prognostic Marker for Changing Viral Load in SHIV-Infected Rhesus Macaques

In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4+ T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4+ T cells, but not CD8+ T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4+ T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation

Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II

<p>Abstract</p> <p>Background</p> <p>One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder.</p> <p>Methods and design</p> <p>We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD.</p> <p>The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach.</p> <p>Discussion</p> <p>Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.</p

Was There Unmet Mental Health Need After the September 11, 2001 Terrorist Attacks?

Background This study examined the use of professionals for mental health problems among New York City residents who were directly affected by the September 11, 2001 terrorist attacks on the World Trade Center (WTC) or had a probable diagnosis of post-traumatic stress disorder (PTSD) or depression in its aftermath. Correlates of help seeking from professionals for mental health problems after the attacks and barriers to care were also assessed. Method Data were from a random digit dial telephone survey of 2,752 adults representative of the Greater New York Metropolitan area conducted 6 months after the September 11 terrorist attacks. Results Fifteen percent of those directly affected and 36% of those with probable PTSD or depression sought help from a professional for a mental health problem after the attacks. There was little new utilization of professionals for mental health problems after the attacks among persons who were not already receiving care prior to September 11. Barriers that prevented people from seeking help for mental health problems 6 months after the September 11 attacks included traditional barriers to care (e.g., cost) and barriers that are unique to the post-disaster context (e.g., the belief that others need the services more than oneself). Conclusions This study suggests that there was potential unmet mental health need in New York City 6 months after the September 11 attacks on the WTC, but these findings should be tempered by research showing an apparent decrease in populationrates of PTSD. In the aftermath of a disaster, interventions should target persons with mental health needs who were not previously seeking help from a professional for a mental health problem.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40299/2/Stuber_Was There Unmet Mental Health Need_2006.pd

Correlates of local safety-related concerns in a Swedish Community : a cross-sectional study

Background: Crime in a neighbourhood has been recognized as a key stressor in the residential environment. Fear of crime is related to risk assessment, which depends on the concentration of objective risk in time and space, and on the presence of subjective perceived early signs of imminent hazard. The aim of the study was to examine environmental, socio-demographic, and personal correlates of safety-related concerns at the local level in urban communities. The specific aim was to investigate such correlates in contiguous neighbourhoods in a Swedish urban municipality. Methods: A cross-sectional study design was used to investigate three neighbourhood settings with two pair-wise conterminous but socially contrasting areas within each setting. Crime data were retrieved from police records. Study data were collected through a postal questionnaire distributed to adult residents (n = 2476) (response rate 56%). Composite dimensions of perceived residential safety were derived through a factor analysis. Logistic regression analysis was used to examine associations between high-level scores of the three safety-related dimensions and area-level crime rate, being a victim of crime, area reputation, gender, age, education, country of birth, household civil status and type of housing. Results: Three composite dimensions of perceived residential safety were identified: (I) structural indicators of social disorder; (II) contact with disorderly behavior; and (III) existential insecurity. We found that area-level crime rates and individual-level variables were associated with the dimensions structural indicators of social disorder and existential insecurity, but only individual-level variables were associated with the dimension contact with disorderly behavior. Self-assessed less favorable area reputation was found to be strongly associated with all three factors. Being female accorded existential insecurity more than being a victim of crime. Conclusion: We have identified environmental, socio-demographic, and personal correlates of safety-related concerns in contiguous neighbourhoods in a Swedish community. The results of this study suggest that residents self-assessed area reputation is an important underlying mechanism of perceived safety. We also found a difference in crime rates and safety-related concerns between areas with blocks of flats compared with small-scale areas although the neighbourhoods were close geographically.Original Publication:Agneta Kullberg, Nadine Karlsson, Toomas Timpka and Kent Lindqvist, Correlates of local safety-related concerns in a Swedish Community: a cross-sectional study, 2009, BMC PUBLIC HEALTH, (9), 221.http://dx.doi.org/10.1186/1471-2458-9-221Licensee: BioMed Centralhttp://www.biomedcentral.com