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

Demonstration of Cross-Protective Vaccine Immunity against an Emerging Pathogenic Ebolavirus Species

A major challenge in developing vaccines for emerging pathogens is their continued evolution and ability to escape human immunity. Therefore, an important goal of vaccine research is to advance vaccine candidates with sufficient breadth to respond to new outbreaks of previously undetected viruses. Ebolavirus (EBOV) vaccines have demonstrated protection against EBOV infection in nonhuman primates (NHP) and show promise in human clinical trials but immune protection occurs only with vaccines whose antigens are matched to the infectious challenge species. A 2007 hemorrhagic fever outbreak in Uganda demonstrated the existence of a new EBOV species, Bundibugyo (BEBOV), that differed from viruses covered by current vaccine candidates by up to 43% in genome sequence. To address the question of whether cross-protective immunity can be generated against this novel species, cynomolgus macaques were immunized with DNA/rAd5 vaccines expressing ZEBOV and SEBOV glycoprotein (GP) prior to lethal challenge with BEBOV. Vaccinated subjects developed robust, antigen-specific humoral and cellular immune responses against the GP from ZEBOV as well as cellular immunity against BEBOV GP, and immunized macaques were uniformly protected against lethal challenge with BEBOV. This report provides the first demonstration of vaccine-induced protective immunity against challenge with a heterologous EBOV species, and shows that Ebola vaccines capable of eliciting potent cellular immunity may provide the best strategy for eliciting cross-protection against newly emerging heterologous EBOV species

Cigarette smoking, nicotine dependence and anxiety disorders : a systematic review of population-based, epidemiological studies

Background Multiple studies have demonstrated that rates of smoking and nicotine dependence are increased in individuals with anxiety disorders. However, significant variability exists in the epidemiological literature exploring this relationship, including study design (cross-sectional versus prospective), the population assessed (random sample versus clinical population) and diagnostic instrument utilized.Methods We undertook a systematic review of population-based observational studies that utilized recognized structured clinical diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD)) for anxiety disorder diagnosis to investigate the relationship between cigarette smoking, nicotine dependence and anxiety disorders.Results In total, 47 studies met the predefined inclusion criteria, with 12 studies providing prospective information and 5 studies providing quasiprospective information. The available evidence suggests that some baseline anxiety disorders are a risk factor for initiation of smoking and nicotine dependence, although the evidence is heterogeneous and many studies did not control for the effect of comorbid substance use disorders. The identified evidence however appeared to more consistently support cigarette smoking and nicotine dependence as being a risk factor for development of some anxiety disorders (for example, panic disorder, generalized anxiety disorder), although these findings were not replicated in all studies. A number of inconsistencies in the literature were identified.Conclusions Although many studies have demonstrated increased rates of smoking and nicotine dependence in individuals with anxiety disorders, there is a limited and heterogeneous literature that has prospectively examined this relationship in population studies using validated diagnostic criteria. The most consistent evidence supports smoking and nicotine dependence as increasing the risk of panic disorder and generalized anxiety disorder. The literature assessing anxiety disorders increasing smoking and nicotine dependence is inconsistent. Potential issues with the current literature are discussed and directions for future research are suggested

The Voices of Survivors Documentary: Using Patient Narrative to Educate Physicians About Domestic Violence

This article describes a method of developing physician education materials using analysis of domestic violence patient experiences and patients' descriptions of their experiences. The process began with interviews of 21 domestic violence survivors, focusing on what they wanted to teach physicians. Qualitative analysis of these interviews identified 4 main themes regarding what survivors wanted physicians to understand about life in an abusive relationship: that domestic violence is universal, that it is more than just physical assaults, that it is all about power and control, and that it affects the entire family. Because what survivors wanted from physicians differed depending on where they were in their abusive relationships, recommendations were developed for each of 5 common situations: when a patient may not yet recognize the abuse, when s/he may not be ready or able to disclose the abuse, when s/he chooses to remain in an abusive relationship, when s/he is seeking care for an acute assault, and when s/he has left the relationship but not yet healed. Interview excerpts representing each of the identified themes are used to create a 30-minute educational documentary. A written companion guide covers the traditional aspects of domestic violence education. In teaching about domestic violence or other health problems where it is difficult for physicians to understand their patients intuitively, an educator's most important role may be to direct learners to listen to the experience and wisdom of patients

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