IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

The Shine-Through Masking Paradigm Is a Potential Endophenotype of Schizophrenia

BACKGROUND: To understand the genetics of schizophrenia, a hunt for so-called intermediate phenotypes or endophenotypes is ongoing. Visual masking has been proposed to be such an endophenotype. However, no systematic study has been conducted yet to prove this claim. Here, we present the first study showing that masking meets the most important criteria for an endophenotype. METHODOLOGY/PRINCIPAL FINDINGS: We tested 62 schizophrenic patients, 39 non-affected first-degree relatives, and 38 healthy controls in the shine-through masking paradigm and, in addition, in the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). Most importantly, masking performance of relatives was significantly in between the one of patients and controls in the shine-through paradigm. Moreover, deficits were stable throughout one year. Using receiver operating characteristics (ROC) methods, we show that the shine-through paradigm distinguishes with high sensitivity and specificity between schizophrenic patients, first-order relatives and healthy controls. CONCLUSIONS/SIGNIFICANCE: The shine-through paradigm is a potential endophenotype

Genetic control of chicken heterophil function in advanced intercross lines: associations with novel and with known Salmonella resistance loci and a likely mechanism for cell death in extracellular trap production

Heterophils, the avian polymorphonuclear leukocyte and the counterpart of mammalian neutrophils, generate the primary innate response to pathogens in chickens. Heterophil performance against pathogens is associated with host disease resistance, and heterophil gene expression and function are under genetic control. To characterize the genomic basis of heterophil function, heterophils from F13 advanced intercross chicken lines (broiler × Leghorn and broiler × Fayoumi) were assayed for phagocytosis and killing of Salmonella enteritidis, oxidative burst, and extracellular trap production. A whole-genome association analysis of single nucleotide polymorphisms at 57,636 loci identified genomic locations controlling these functional phenotypes. Genomic analysis revealed a significant association of extracellular trap production with the SAL1 locus and the SLC11A1 gene, which have both been previously associated with resistance to S. enteritidis. Fine mapping supports SIVA1 as a candidate gene controlling SAL1-mediated resistance and indicates that the proposed cell-death mechanism associated with extracellular trap production, ETosis, likely functions through the CD27/Siva-1-mediated apoptotic pathway. The SLC11A1 gene was also associated with phagocytosis of S. enteritidis, suggesting that the Slc11a1 protein may play an additional role in immune response beyond depleting metal ions to inhibit intracellular bacterial growth. A region of chromosome 6 with no characterized genes was also associated with extracellular trap production. Further characterization of these novel genes in chickens and other species is needed to understand their role in polymorphonuclear leukocyte function and host resistance to disease

Factors associated with problem drinking among women employed in food and recreational facilities in northern Tanzania.

BACKGROUND: There is growing evidence that alcohol consumption is associated with increased risk of HIV infection. To determine factors associated with problem drinking, we analyzed data collected in two prospective cohorts of at-risk female food and recreational facility workers in northern Tanzania. METHODS: We enrolled HIV seronegative women aged 18-44 years and employed in the towns of Geita, Kahama, Moshi, and Shinyanga. At enrolment, women were interviewed to obtain information about alcohol use, using CAGE and AUDIT screening scales, and risk factors for HIV infection. Blood and genital samples were collected for detection of HIV and sexually transmitted infections (STIs). We characterized alcohol use, concordance, and agreement of the scales, and examined the associations between characteristics of participants and problem drinking as defined by both scales using logistic regression. Lastly, we assessed problem drinking as a risk factor for recent sexual behavior and prevalent STIs. RESULTS: Among enrollees, 68% women reported ever drinking alcohol; of these 76% reported drinking alcohol in the past 12 months. The prevalence of problem drinking was 20% using CAGE and 13% using AUDIT. Overall concordance between the scales was 75.0% with a Kappa statistic of 0.58. After adjusting for age, independent factors associated with problem drinking, on both scales, were marital status, occupation, facility type, increasing number of lifetime sexual partners, and transactional sex in the past 12 months. In addition, women who were problem drinkers on either scale were more likely to report having ≥ 1 sexual partner (CAGE: aOR = 1.56, 95% confidence interval, CI: 1.10-2.23; AUDIT: aOR = 2.00, 95% CI: 1.34-3.00) and transactional sex (CAGE: aOR = 1.79, 95% CI: 1.26-2.56; AUDIT: aOR = 1.51, 95% CI: 1.04-2.18), in the past 3 months. CONCLUSION: These findings suggest that interventions to reduce problem drinking in this population may reduce high-risk sexual behaviors and contribute in lowering the risk of HIV infection

Fats and Factors: Lipid Profiles Associate with Personality Factors and Suicidal History in Bipolar Subjects

Polyunsaturated fatty acids (PUFA) have shown efficacy in the treatment of bipolar disorder, however their specific role in treating the illness is unclear. Serum PUFA and dietary intakes of PUFA associate with suicidal behavior in epidemiological studies. The objective of this study was to assess serum n-3 and n-6 PUFA levels in bipolar subjects and determine possible associations with suicidal risk, including suicidal history and relevant personality factors that have been associated with suicidality. We studied 27 bipolar subjects using the NEO-PI to assess the big five personality factors, structured interviews to verify diagnosis and assess suicidal history, and lipomics to quantify n-3 and n-6 PUFA in serum. We found positive associations between personality factors and ratios of n-3 PUFA, suggesting that conversion of short chain to long chain n-3s and the activity of enzymes in this pathway may associate with measures of personality. Thus, ratios of docosahexaenoic acid (DHA) to alpha linolenic acid (ALA) and the activity of fatty acid desaturase 2 (FADS2) involved in the conversion of ALA to DHA were positively associated with openness factor scores. Ratios of eicosapentaenoic acid (EPA) to ALA and ratios of EPA to DHA were positively associated with agreeableness factor scores. Finally, serum concentrations of the n-6, arachidonic acid (AA), were significantly lower in subjects with a history of suicide attempt compared to non-attempters. The data suggest that specific lipid profiles, which are controlled by an interaction between diet and genetics, correlate with suicidal history and personality factors related to suicidal risk. This study provides preliminary data for future studies to determine whether manipulation of PUFA profiles (through diet or supplementation) can affect personality measures and disease outcome in bipolar subjects and supports the need for further investigations into individualized specific modulations of lipid profiles to add adjunctive value to treatment paradigms

Discussing Uncertainty and Risk in Primary Care: Recommendations of a Multi-Disciplinary Panel Regarding Communication Around Prostate Cancer Screening

BACKGROUND: Shared decision making improves value-concordant decision-making around prostate cancer screening (PrCS). Yet, PrCS discussions remain complex, challenging and often emotional for physicians and average-risk men. OBJECTIVE: In July 2011, the Centers for Disease Control and Prevention convened a multidisciplinary expert panel to identify priorities for funding agencies and development groups to promote evidence-based, value-concordant decisions between men at average risk for prostate cancer and their physicians. DESIGN: Two-day multidisciplinary expert panel in Atlanta, Georgia, with structured discussions and formal consensus processes. PARTICIPANTS: Sixteen panelists represented diverse specialties (primary care, medical oncology, urology), disciplines (sociology, communication, medical education, clinical epidemiology) and market sectors (patient advocacy groups, Federal funding agencies, guideline-development organizations). MAIN MEASURES: Panelists used guiding interactional and evaluation models to identify and rate strategies that might improve PrCS discussions and decisions for physicians, patients and health systems/society. Efficacy was defined as the likelihood of each strategy to impact outcomes. Effort was defined as the relative amount of effort to develop, implement and sustain the strategy. Each strategy was rated (1–7 scale; 7 = maximum) using group process software (ThinkTank(TM)). For each group, intervention strategies were grouped as financial/regulatory, educational, communication or attitudinal levers. For each strategy, barriers were identified. KEY RESULTS: Highly ranked strategies to improve value-concordant shared decision-making (SDM) included: changing outpatient clinic visit reimbursement to reward SDM; development of evidence-based, technology-assisted, point-of-service tools for physicians and patients; reframing confusing prostate cancer screening messages; providing pre-visit decision support interventions; utilizing electronic health records to promote benchmarking/best practices; providing additional training for physicians around value-concordant decision-making; and using re-accreditation to promote training. CONCLUSIONS: Conference outcomes present an expert consensus of strategies likely to improve value-concordant prostate cancer screening decisions. In addition, the methodology used to obtain agreement provides a model of successful collaboration around this and future controversial cancer screening issues, which may be of interest to funding agencies, educators and policy makers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-013-2419-z) contains supplementary material, which is available to authorized users

The effect of parental rearing conditions on offspring life history in Anopheles stephensi

Background The environmental conditions experienced by parents are increasingly recognized to impact the success of offspring. Little is known on the presence of such parental effects in Anopheles. If present, parental effects could influence mosquito breeding programmes, some malaria control measures and have epidemiological and evolutionary consequences. Methods The presence of parental effects on offspring emergence time, size, survival, blood meal size and fecundity in laboratory reared An. stephensi were tested. Results Parental rearing conditions did not influence the time taken for offspring to emerge, or their size or survival as adults. However, parental effects were influential in determining the fecundity of daughters. Counter-intuitively, daughters of parents reared in low food conditions produced larger egg clutches than daughters of parents reared in high food conditions. Offspring reared in low food conditions took larger blood meals if their parents had also experienced a low food environment. Conclusion So far as we are aware, this is the first evidence of parental effects on progeny in Anophele

Attachment and coping in psychosis in relation to spiritual figures

Background: Studies have found higher levels of insecure attachment in individuals with schizophrenia. Attachment theory provides a framework necessary for conceptualizing the development of interpersonal functioning. Some aspects of the attachment of the believer to his/her spiritual figure are similar to those between the child and his/her parents. The correspondence hypothesis suggests that early child-parent interactions correspond to a person's relation to a spiritual figure. The compensation hypothesis suggests that an insecure attachment history would lead to a strong religiousness/spirituality as a compensation for the lack of felt security. The aim of this study is to explore attachment models in psychosis vs. healthy controls, the relationships between attachment and psychopathology and the attachment processes related to spiritual figures. Methods: Attachment models were measured in 30 patients with psychosis and 18 controls with the AAI (Adult Attachment interview) in relationship with psychopathology. Beliefs and practices related to a spiritual figure were investigated by qualitative and quantitative analyses. Results: Patients with psychosis showed a high prevalence of insecure avoidant attachment. Spiritual entities functioned like attachment figures in two thirds of cases. Interviews revealed the transformation of internal working models within relation to a spiritual figure: a compensation process was found in 7 of the 32 subjects who showed a significant attachment to a spiritual figure. Conclusions: Attachment theory allows us to highlight one of the underlying dimensions of spiritual coping in patients with psychosis