In vivo clonal expansion and phenotypes of hypocretin-specific CD4(+) T cells in narcolepsy patients and controls

Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor alpha (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer(+)/TRAJ24(+)/CD4(+) T cells in DQ6(+) individuals with and without narcolepsy. We identify related TRAJ24(+) TCRalphabeta clonotypes encoded by identical alpha/beta gene regions from two patients and two controls. TRAJ24-G allele(+) clonotypes only expand in the two patients, whereas a TRAJ24-C allele(+) clonotype expands in a control. A representative tetramer(+)/G-allele(+) TCR shows signaling reactivity to the epitope HCRT87-97. Clonally expanded G-allele(+) T cells exhibit an unconventional effector phenotype. Our analysis of in vivo expansion of HCRT-reactive TRAJ24(+) cells opens an avenue for further investigation of the autoimmune contribution to narcolepsy development

"I Didn't Want To Be 'That Girl'": The Social Risks of Labeling, Telling, and Reporting Sexual Assault

This article deploys ethnographic data to explain why some students do not label experiences as sexual assault or report those experiences. Using ideas of social risks and productive ambiguities, it argues that not labeling or reporting assault can help students (1) sustain their current identities and allow for several future ones, (2) retain their social relationships and group affiliations while maintaining the possibility of developing a wider range of future ones, or (3) avoid derailing their current or future goals within the higher educational setting, or what we call "college projects." Conceptually, this work advances two areas of sociological research. First, it expands the framework of social risks, or culturally specific rationales for seemingly illogical behavior, by highlighting the interpersonal and institutional dimensions of such risks. Second, it urges researchers to be more attentive to contexts in which categorical ambiguity or denial is socially productive and to take categorical avoidance seriously as a subject of inquiry. Substantively, this work advances knowledge of why underreporting of campus sexual assault occurs, with implications for institutional policies to support students who have experienced unwanted nonconsensual sex regardless of how those students may label what happened

The importance of physical and mental health in explaining health-related academic role impairment among college students

Research consistently documents high rates of mental health problems among college students and strong associations of these problems with academic role impairment. Less is known, though, about prevalence and effects of physical health problems in relation to mental health problems. The current report investigates this by examining associations of summary physical and mental health scores from the widely-used Short-Form 12 (SF-12) Health Survey with self-reported academic role functioning in a self-report survey of 3,855 first-year students from five universities in the northeastern United States (US; mean age 18.5; 53.0% female). The mean SF-12 physical component summary (PCS) score (55.1) was half a standard deviation above the benchmark US adult population mean. The mean SF-12 mental component summary (MCS) score (38.2) was more than a full standard deviation below the US adult population mean. Two-thirds of students (67.1%) reported at least mild and 10.5% severe health-related academic role impairment on a modified version of the Sheehan Disability Scale. Both PCS and MCS scores were significantly and inversely related to these impairment scores, but with nonlinearities and interactions and much stronger associations involving MCS than PCS. Simulation suggests that an intervention that improved the mental health of all students with scores below the MCS median to be at the median would result in a 61.3% reduction in the proportion of students who experienced severe health-related academic role impairment. Although low-cost scalable interventions exist to address student mental health problems, pragmatic trials are needed to evaluate the effectiveness of these interventions in reducing academic role impairment

HIV Prevention in Care and Treatment Settings: Baseline Risk Behaviors among HIV Patients in Kenya, Namibia, and Tanzania.

HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV) with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538). Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP). TRIAL REGISTRATION: ClinicalTrials.gov NCT01256463

Implementation of a comprehensive program including psycho-social and treatment literacy activities to improve adherence to HIV care and treatment for a pediatric population in Kenya

BACKGROUND: To achieve good clinical outcomes with HAART, patient adherence to treatment and care is a key factor. Since the literature on how to care for pediatric HIV patients is limited, we describe here adherence interventions implemented in our comprehensive care program in a resource-limited setting in Kenya. METHODS: We based our program on factors reported to influence adherence to HIV care and treatment. We describe, in detail, our program with respect to how we adapted our clinical settings, implemented psycho-social support activities for children and their caregivers and developed treatment literacy for children and teenagers living with HIV/AIDS. RESULTS: This paper focused on the details of the program, with the treatment outcomes as secondary. However, our program appeared to have been effective; for 648 children under 15 years of age who were started on HAART, the Kaplan-Meier mortality survival estimate was 95.27% (95%CI 93.16-96.74) at 12 months after the time of initiation of HAART. CONCLUSION: Our model of pediatric HIV/AIDS care, focused on a child-centered approach with inclusion of caregivers and extended family, addressed the main factors influencing treatment adherence. It appeared to produce good results and is replicable in resource-limited settings

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: Clinical and therapeutic implications

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways

Cognitive and psychosocial development of HIV pediatric patients receiving highly active anti-retroviral therapy: a case-control study

<p>Abstract</p> <p>Background</p> <p>The psychosocial development of pediatric HIV patients has not been extensively evaluated. The study objectives were to evaluate whether emotional and social functions are differentially associated with HIV-related complications.</p> <p>Methods</p> <p>A matched case-control study design was conducted. The case group (n = 20) consisted of vertically infected children with HIV (aged 3-18 years) receiving HAART in Greece. Each case was matched with two randomly selected healthy controls from a school-based population. CNS imaging and clinical findings were used to identify patients with HIV-related neuroimaging abnormalities. The Wechsler Intelligence Scale III and Griffiths Mental Abilities Scales were applied to assess cognitive abilities. The age specific Strengths and Difficulties Questionnaire was used to evaluate emotional adjustment and social skills. The Fisher's exact test, student's t-test, and Wilcoxon rank sum test were used to compare categorical, continuous, and ordinal scores, respectively, of the above scales between groups.</p> <p>Results</p> <p>HIV patients without neuroimaging abnormalities did not differ from patients with neuroimaging abnormalities with respect to either age at HAART initiation (p = 0.306) or months of HAART treatment (p = 0.964). While HIV patients without neuroimaging abnormalities had similar cognitive development with their healthy peers, patients with neuroimaging abnormalities had lower mean General (p = 0.027) and Practical (p = 0.042) Intelligence Quotient scores. HIV patients without neuroimaging abnormalities had an increased likelihood of both Abnormal Emotional Symptoms (p = 0.047) and Hyperactivity scores (p = 0.0009). In contrast, HIV patients with neuroimaging abnormalities had an increased likelihood of presenting with Abnormal Peer Problems (p = 0.033).</p> <p>Conclusions</p> <p>HIV patients without neuroimaging abnormalities are more likely to experience maladjustment with respect to their emotional and activity spheres, while HIV patients with neuroimaging abnormalities are more likely to present with compromised social skills. Due to the limited sample size and age distribution of the study population, further studies should investigate the psychosocial development of pediatric HIV patients following the disclosure of their condition.</p

Factors Associated with HIV/AIDS Diagnostic Disclosure to HIV Infected Children Receiving HAART: A Multi-Center Study in Addis Ababa, Ethiopia

BACKGROUND: Diagnostic disclosure of HIV/AIDS to a child is becoming an increasingly common issue in clinical practice. Nevertheless, some parents and health care professionals are reluctant to inform children about their HIV infection status. The objective of this study was to identify the proportion of children who have knowledge of their serostatus and factors associated with disclosure in HIV-infected children receiving HAART in Addis Ababa, Ethiopia. METHODS: A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18, 2008-April 28, 2008. The study populations were parents/caretakers and children living with HIV/AIDS who were receiving Highly Active Antiretroviral Therapy (HAART) in selected hospitals in Addis Ababa. Univariate and multivariate logistic regression analysis were carried out using SPSS 12.0.1 statistical software. RESULTS: A total of 390 children/caretaker pairs were included in the study. Two hundred forty three children (62.3%) were between 6-9 years of age. HIV/AIDS status was known by 68 (17.4%) children, 93 (29%) caretakers reported knowing the child's serostatus two years prior to our survey, 180 (46.2%) respondents said that the child should be told about his/her HIV/AIDS status when he/she is older than 14 years of age. Children less than 9 years of age and those living with educated caregivers are less likely to know their results than their counterparts. Children referred from hospital's in-patient ward before attending the HIV clinic and private clinic were more likely to know their results than those from community clinic. CONCLUSION: The proportion of disclosure of HIV/AIDS diagnosis to HIV-infected children is low. Strengthening referral linkage and health education tailored to educated caregivers are recommended to increase the rate of disclosure

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. METHODS: We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. RESULTS: The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. CONCLUSIONS: The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways