HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.     

A Mixed Methods Examination of Health Care Provider Behaviors That Build Patients’ Trust

ObjectivePatient trust in health care providers is associated with better health behaviors and utilization, yet provider trust has not been consistently conceptualized. This study uses qualitative methods to identify the key health provider behaviors that patients report build their trust, and data from a national U.S. survey of adults to test the robustness of the qualitative findings.MethodsIn this mixed methods study, we conducted 40 semi-structured interviews with a diverse sample to identify the provider behaviors that build trust. We then analyzed a nationally representative survey (n = 6,517) to examine the relationship between respondents’ trust in their usual provider and the key trust-related behaviors identified in the qualitative interviews.ResultsInterviewees reported that health providers build trust by communicating effectively (listening and providing detailed explanations), caring about their patients (treating them as individuals, valuing their experience, and showing commitment to solving their health issues), and demonstrating competence (being knowledgeable, thorough, and solving their health issues). Trust in one’s provider was highly correlated with all eight survey items measuring communication, caring, and competence.ConclusionsTo build trust with patients, health providers should actively listen, provide detailed explanations, show caring for patients, and demonstrate their knowledge.     

Sexual Desire among Veterans Receiving Prolonged Exposure Therapy for PTSD: Does Successful PTSD Treatment Also Yield Improvements in Sexual Desire?

Objective: People with posttraumatic stress disorder (PTSD) commonly report difficulties with sexual desire and other aspects of sexual functioning, but it is currently unknown if people who respond to psychotherapy for PTSD also report improvements in sexual desire. Method: One hundred and eighty-seven veterans with PTSD received prolonged exposure (PE) therapy at two outpatient PTSD specialty clinics and completed measures of PTSD symptoms (the PTSD Checklist – Military Version) and sexual desire (item 21 of the Beck Depression Inventory – Second Edition) repeatedly throughout the course of treatment. Results: The results of a conditional generalized mixed ordinal regression model showed a significant interaction between weeks in treatment and PTSD treatment response in predicting change in sexual desire across the course of treatment. Specifically, PTSD treatment responders reported improvement in sexual desire over the course of treatment, whereas nonresponders did not show changes in sexual desire over time. However, the effect of PTSD treatment response was no longer significant when accounting for severity of depression at the start of treatment. Participants reporting more severe depression at the start of treatment reported less improvement in sexual desire, regardless of PTSD symptom response. Conclusions: People with PTSD who respond to PE also report improvements in sexual desire over time, indicating that response to PE is associated with improved sexual desire, but the effect is complicated by the presence of co-occurring depression symptomatology.     

Influenza Knowledge,Attitude, and Behavior Survey for Grade School Students: Design and Novel Assessment Methodology

Despite the fact infectious diseases can spread readily in grade schools, few studies have explored prevention in this setting. Additionally, we lack valid tools for students to self-report knowledge, attitudes, and behaviors. As part of an ongoing study of a curriculum intervention to promote healthy behaviors, we developed and evaluated age-appropriate surveys to determine students’ understanding of influenza prevention. Surveys were adapted from adolescent and adult influenza surveys and administered to students in grades 2–5 (ages 7–11) at two Rochester public schools. We assessed student understanding by analyzing percent repeatability of 20 survey questions and compared percent “don’t know” (DK) responses across grades, gender, and race. Questions thought to be ambiguous after early survey administration were investigated in student focus groups, modified as appropriate, and reassessed. The response rate across all surveys was >87 %. Survey questions were well understood; 16 of 20 questions demonstrated strong pre/post repeatability (>70 %). Only 1 question showed an increase in DK response for higher grades (p < .0001). Statistical analysis and qualitative feedback led to modification of 3 survey questions and improved measures of understanding in the final survey administration. Grade-school students’ knowledge, attitudes and behavior toward influenza prevention can be assessed using surveys. Quantitative and qualitative analysis may be used to assess participant understanding and refine survey development for pediatric survey instruments. These methods may be used to assess the repeatability and validity of surveys to assess the impact of health education interventions in young children.     

Cloning of a cDNA encoding phosphoenolpyruvate carboxykinase from Haemonchus contortus.

Biochemical and metabolic data have led to the conclusion that the enzyme phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) contributes to a critical point of divergence in energy conservation pathways between mammals and nematodes. To facilitate the determination of the molecular basis for host vs parasite differences in PEPCK, we have cloned a cDNA encoding this enzyme from a parasitic nematode of ruminants, Haemonchus contortus. H. contortus PEPCK was cloned by functional complementation of a PEPCK, malic enzyme strain of Escherichia coli (E1786) using an egg stage H. contortus cDNA library in λZAPII. Selection was for growth on malate as the sole carbon source (malate phenotype). We isolated a plasmid, pPEPCK, which reproducibly confers a malate phenotype in E1786. The sequence of the 2.0-kb EcoRI insert of pPEPCK predicts a 612-amino acid protein which shows about 74% similarity to Drosophila melanogaster and chicken PEPCK. Extracts of E1786[pPEPCK], but not E1786, contain IDP- or GDP-dependent PEPCK enzyme activity. Sequence analysis revealed that the open reading frame (ORF) in pPEPCK lacked a 5′ initiation codon and was probably expressed as an in-frame fusion protein with β-galactosidase. A strategy combining library screening with PCR analysis of positive clones led to the identification of a clone encoding 6 additional NH₂-terminal amino acids, including a Met, which, by comparison with known PEPCK amino acid sequences, is likely to be the translation initiation site.     

T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice

Resolution of a HSV-2 infection of the female genital tract has been shown to be T-cell dependent. The T-cell populations and mechanisms involved in clearance of virus from the genital epithelium were examined in this study. T lymphocytes expressing either alphabeta or gammadelta T-cell receptors (TCR) have been detected in the vaginal epithelium of mice. The involvement of gammadelta T cells in HSV-2 clearance was tested by intravaginal (ivag) challenge of mice depleted of alphabeta T cells by administration of specific antibodies and of mice lacking gammadelta T cells due to specific deletion of the delta TCR gene. The results of these studies strongly suggest that gammadelta T cells are not required for or involved in clearance of HSV-2 from the genital epithelium. Mechanisms of virus clearance employed by alphabeta T cells were also examined. Although HSV-specific lytic activity could be demonstrated ex vivo in populations of vaginal exudate cells from HSV-infected mice, clearance of virus did not require either perforin- or Fas/Fas ligand (FasL)-dependent cytolytic pathways. In contrast, virus resolution was significantly impaired following neutralization of interferon-gamma (IFN-gamma), but not tumor necrosis factor-alpha (TNF-alpha). Together, these results suggest that non-lytic mechanisms mediated by alphabeta T cells were responsible for resolution of a genital HSV-2 infection.     

Efficacy of genital T cell responses to herpes simplex virus type 2 resulting from immunization of the nasal mucosa

Intravaginal (ivag) or intranasal (i.n.) immunization of C57BL/6J (B6) mice with a thymidine kinase-deficient strain (tk-) of herpes simplex virus type 2 (HSV-2) resulted in comparable protection of the genital epithelium and sensory ganglia against HSV-2 challenge. In contrast, protection of these sites was much reduced in i.n.-immunized compared to ivag-immunized B cell-deficient microMT mice. Fewer HSV-specific T cells were detected in the genital epithelium of i.n.-immunized compared to ivag-immunized microMT mice after HSV-2 challenge. Passive transfer of HSV-specific serum to immune microMT mice restored protection of these sites against HSV-2 challenge. These results suggest that protection of genital and neuronal sites may be conferred by i.n. immunization but may be more dependent on antibody-dependent mechanisms than the protection resulting from genital immunization. These results have implications for immunization strategies to elicit high levels of cell-mediated protection of the genital tract and sensory ganglia.