The influence of maternal HIV and Mycobacterium tuberculosis infection on infant immune responses to childhood vaccinations

Background: Altered immune responses might contribute to the high morbidity and mortality observed amongst uninfected infants exposed to human immunodeficiency virus-1 (HIV) in utero. This study examined the influence of maternal HIV and Mycobacterium tuberculosis (Mtb) infection on infant immune responses to immunisation. Methods: 109 mother-infant pairs were enrolled from Khayelitsha, Cape Town, South Africa, and were followed for four months. Peripheral blood samples were collected from mother-infant pairs at delivery and from infants at 16 weeks of age, following routine immunisations. Responses to BCG antigens were measured using multi-parameter flow cytometry and multiplex enzyme-linked immunosorbent assays (ELISAs). Specific antibody levels to Haemophilus influenzae type B (Hib), pneumococcus, Bordetella pertussis, tetanus toxoid and hepatitis B surface antigen were determined by ELISA. Results: At birth, HIV-exposed, uninfected infants had increased frequencies of proliferating T cells expressing TNF-α and increased levels of TNF-α protein in cell culture supernatants; levels were highest amongst HIV-exposed infants born to Mtb sensitised mothers. IFN-γ levels were lower amongst HIV-exposed, uninfected infants compared to unexposed infants. Maternal Mtb sensitisation was associated with increased infant IFN-γ levels at birth; infants born to HIV-infected, Mtb-sensitised mothers had similar levels IFN-γ compared to unexposed infants. Following BCG vaccination at 6 weeks of age, the immune response to infant BCG vaccination was unaffected by maternal HIV infection of Mtb sensitisation. Amongst mothers, Mtb sensitisation significantly influenced the response to BCG-antigens in HIV-infected but not in HIV-uninfected mothers. HIV-exposed, uninfected infants had lower specific antibody responses compared with unexposed infants at birth, but had robust responses following immunisation. Deficits in humoral protection against vaccine-preventable diseases were observed amongst HIV infected and HIV-uninfected women. Conclusions: Antenatal HIV exposure was associated with alterations in immune response to vaccine antigens at birth, however HIV-exposed infants had comparable potentical to respond to immunisation

The research-teaching nexus : what do national teaching awards tells us?

This article addresses two questions that are part of a broader debate about the relationship between teaching and research: are outstanding university teachers engaged in research and are they disseminating their teaching expertise to other university teachers? We address these questions through an analysis of the research and publications of the 2005 winners of the competitive, national awards for university teaching in Australia. The analysis indicates that outstanding university teachers are active researchers, but are unlikely to publish about their teaching or improving teaching practice in universities. The findings have policy implications for the separation of teaching and research within and between universities, and raise questions about the contribution of teaching awards to the wider improvement of university teaching. As such, the article issues a caution to policy makers and university administrators against making pre‐emptive decisions about the relationship between teaching and research based on questionable assumptions.<br /

The relationship between Bipolar Disorder and Cannabis use in daily life:an experience sampling study

Objectives Although cannabis use is common in bipolar disorder and may contribute to worse clinical outcomes, little is understood about the relationship between this drug and bipolar disorder over the course of daily life. The aim of study was to examine the effect of cannabis on affect and bipolar symptoms in a group of individuals with bipolar disorder. Methods Twenty-four participants with bipolar disorder type I or type II completed diaries for 6 days using Experience Sampling Methodology to investigate the temporal associations between cannabis, affect and bipolar disorder symptoms. Results The results indicated that higher levels of positive affect increase the odds of using cannabis (OR:1.25 ,CI:1.06–1.47, P=0.008). However, neither negative affect, manic nor depressive symptoms predicted the use of cannabis. Cannabis use was associated with subsequent increases in positive affect (β=0.35, CI:0.20-0.51, P=0.000), manic symptoms (β=0.20,CI:0.05-0.34, P=0.009) and depressive symptoms (β= 0.17,CI:0.04-0.29, P=0.008). Conclusion The findings indicate that cannabis use is associated with a number of subsequent psychological effects. However there was no evidence that individuals with BD were using cannabis to self-medicate minor fluctuations in negative affect or bipolar disorder symptoms over the course of daily life. The findings in relation to existing literature and clinical implications are discussed

Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study

<p>Abstract</p> <p>Background</p> <p>Complaints of unrefreshing sleep are a prominent component of chronic fatigue syndrome (CFS); yet, polysomnographic studies have not consistently documented sleep abnormalities in CFS patients. We conducted this study to determine whether alterations in objective sleep characteristics are associated with subjective measures of poor sleep quality in persons with CFS.</p> <p>Methods</p> <p>We examined the relationship between perceived sleep quality and polysomnographic measures of nighttime and daytime sleep in 35 people with CFS and 40 non-fatigued control subjects, identified from the general population of Wichita, Kansas and defined by empiric criteria. Perceived sleep quality and daytime sleepiness were assessed using clinical sleep questionnaires. Objective sleep characteristics were assessed by nocturnal polysomnography and daytime multiple sleep latency testing.</p> <p>Results</p> <p>Participants with CFS reported unrefreshing sleep and problems sleeping during the preceding month significantly more often than did non-fatigued controls. Participants with CFS also rated their quality of sleep during the overnight sleep study as significantly worse than did control subjects. Control subjects reported significantly longer sleep onset latency than latency to fall asleep as measured by PSG and MSLT. There were no significant differences in sleep pathology or architecture between subjects with CFS and control subjects.</p> <p>Conclusion</p> <p>People with CFS reported sleep problems significantly more often than control subjects. Yet, when measured these parameters and sleep architecture did not differ between the two subject groups. A unique finding requiring further study is that control, but not CFS subjects, significantly over reported sleep latency suggesting CFS subjects may have an increased appreciation of sleep behaviour that may contribute to their perception of sleep problems.</p

Psychometric properties of the CDC Symptom Inventory for assessment of Chronic Fatigue Syndrome

OBJECTIVES: Validated or standardized self-report questionnaires used in research studies and clinical evaluation of chronic fatigue syndrome (CFS) generally focus on the assessment of fatigue. There are relatively few published questionnaires that evaluate case defining and other accompanying symptoms in CFS. This paper introduces the self-report CDC CFS Symptom Inventory and analyzes its psychometric properties. METHODS: One hundred sixty-four subjects (with CFS, other fatiguing illnesses and non fatigued controls) identified from the general population of Wichita, Kansas were enrolled. Evaluation included a physical examination, a standardized psychiatric interview, three previously validated self-report questionnaires measuring fatigue and illness impact (Medical Outcomes Survey Short-Form-36 [MOS SF-36], Multidimensional Fatigue Inventory [MFI], Chalder Fatigue Scale), and the CDC CFS Symptom Inventory. Based on theoretical assumptions and statistical analyses, we developed several different Symptom Inventory scores and evaluated them on their ability to differentiate between participants with CFS and non-fatigued controls. RESULTS: The Symptom Inventory had good internal consistency and excellent convergent validity. A Total score (all symptoms), Case Definition score (CFS case defining symptoms) and Short Form score (6 symptoms with minimal correlation) differentiated CFS cases from controls. Furthermore, both the Case Definition and Short Form scores distinguished people with CFS from fatigued subjects who did not meet criteria for CFS. CONCLUSION: The Symptom Inventory appears to be a reliable and valid instrument to assess symptoms that accompany CFS. It is a positive addition to existing instruments measuring fatigue because it allows other dimensions of the illness to be assessed. Further research is needed to confirm and replicate the current findings in a normative population

Physical Activity and Survival After Prostate Cancer

AbstractBackgroundDespite the high global prevalence of prostate cancer (PCa), few epidemiologic studies have assessed physical activity in relation to PCa survival.ObjectiveTo evaluate different types, intensities, and timing of physical activity relative to PCa survival.Design, setting, and participantsA prospective study was conducted in Alberta, Canada, in a cohort of 830 stage II–IV incident PCa cases diagnosed between 1997 and 2000 with follow-up to 2014 (up to 17 yr). Prediagnosis lifetime activity was self-reported at diagnosis. Postdiagnosis activity was self-reported up to three times during follow-up.Outcome measurements and statistical analysisCox proportional hazards models related physical activity to all-cause and PCa-specific deaths and to first recurrence/progression of PCa.Results and limitationsA total of 458 deaths, 170 PCa-specific deaths, and, after first follow-up, 239 first recurrences/progressions occurred. Postdiagnosis total activity (>119 vs ≤42 metabolic equivalent [MET]-hours/week per year) was associated with a significantly lower all-cause mortality risk (hazard ratio [HR]: 0.58; 95% confidence interval [CI], 0.42–0.79; p value for trend <0.01). Postdiagnosis recreational activity (>26 vs ≤4 MET-hours/week per year) was associated with a significantly lower PCa-specific mortality risk (HR: 0.56; 95% CI, 0.35–0.90; p value for trend = 0.01). Sustained recreational activity before and after diagnosis (>18–20 vs <7–8 MET-hours/week per year) was associated with a lower risk of all-cause mortality (HR: 0.66; 95% CI, 0.49–0.88). Limitations included generalisability to healthier cases and an observational study design.ConclusionsThese findings support emerging recommendations to increase physical activity after the diagnosis of PCa and would inform a future exercise intervention trial examining PCa outcomes.Patient summaryIn a 17-yr prostate cancer (PCa) survival study, men who survived at least 2 yr who were more physically active postdiagnosis or performed more recreational physical activity before and after diagnosis survived longer. Recreational physical activity after diagnosis was associated with a lower risk of PCa death

Anti-group B Streptococcus antibody in infants born to mothers with human immunodeficiency virus (HIV) infection.

BACKGROUND: HIV-exposed uninfected infants have increased infection risk and mortality compared to HIV-unexposed infants. HIV-exposed infants may be at increased risk of invasive GBS disease due to reduced maternal antibody against GBS. METHODS: We quantified antibodies that bind to the surface of whole Group B Streptococcus (GBS) of serotypes Ia, Ib, II, III and V using novel flow cytometry assays in South African HIV-infected and non-infected mothers and their uninfected infants. Antibody-mediated complement C3b/iC3b deposition onto GBS of these serotypes was also quantified by a novel flow cytometry assay. RESULTS: Geometric mean concentration (GMC) of both surface-binding anti-GBS antibody and antibody-mediated complement deposition onto GBS were reduced in HIV-infected women (n=46) compared to HIV-uninfected women (n=58) for ST1a (surface-binding: 19.3 vs 29.3; p=0.003; complement deposition: 2.9 vs 5.3 SU/mL; p=0.003), STIb (24.9 vs 47.6; p=0.003; 2.6 vs 4.9 SU/mL; p=0.003), STII (19.8 vs 50.0; p=0.001; 3.1 vs 6.2 SU/mL; p=0.001), STIII (27.8 vs 60.1; p=0.001; 2.8 vs 5.3 SU/mL; p=0.001) and STV (121.9 vs 185.6 SU/mL; p<0.001) and in their infants for STIa (complement deposition 9.4 vs 27.0 SU/mL; p=0.02), STIb (13.4 vs 24.5 SU/mL; p=0.02), STII (14.6 vs 42.7 SU/mL; p=0.03), STIII (26.6 vs 62.7 SU/mL; p=0.03) and STV (90.4 vs 165.8 SU/mL; p=0.04). Median transplacental transfer of antibody from HIV-infected women to their infants was reduced compared to HIV-uninfected women for GBS serotypes II (0.42 [IQR 0.22-0.59] vs 1.0 SU/mL [0.42-1.66]; p<0.001), III (0.54 [0.31-1.03] vs 0.95 SU/mL [0.42-3.05], p=0.05) and V (0.51 [0.28-0.79] vs 0.75 SU/mL [0.26-2.9], p=0.04). The differences between infants remained significant at 16 weeks of age. CONCLUSIONS: Maternal HIV infection was associated with lower anti-GBS surface binding antibody concentration and antibody-mediated C3b/iC3b deposition onto GBS bacteria of serotypes Ia, Ib, II, III and V. This may render these infants more susceptible to early and late onset GBS disease