Screening for enteroviral meningitis in infants and children—Is it useful in clinical practice?

Enteroviral meningitis in infants and children commonly leads to hospital admission. Diagnosing viral meningitis can be difficult clinically. We examined the usefulness of enteroviral polymerase chain reaction (PCR) testing using cerebrospinal fluid (CSF) samples on clinical practice by comparing positive enteroviral CSF PCR cases (n = 39/136) to negative controls using both clinical outcomes and laboratory parameters. A positive result correlated with a reduced admission to high dependency unit, reduced the duration of antibiotics and a shorter length of stay (P < .05). Adjusted CSF white cell count > 5/μL correlated with positive PCR (P < .05) but would have missed 32% of cases of enteroviral meningitis. Following these findings, an algorithm for the management of suspected viral meningitis has been introduced.     

Mother–child adrenocortical synchrony: Roles of maternal overcontrol and child developmental phase

An increasing amount of empirical attention is focused on adrenocortical synchrony as an index of biobehavioral co-regulation between parent and child in the context of early child development. Working with an ethnically diverse community sample of children (N = 99, 50.5% male, ages 9–12), we collected saliva samples from mother–child dyads prior to and after a laboratory-based performance challenge task, and tested whether maternal overcontrol and child age moderated dyadic synchrony in cortisol. Results revealed that cortisol levels between mothers and children were significantly positively correlated at pretask for dyads with mean age and older children only, at 25-min post-task for all dyads, and at 45-min post-task for all dyads. Higher overcontrol/older child dyads exhibited a unique pattern of cortisol synchrony wherein at pretask, mother–child levels had the strongest positive correlation, whereas at 25 and 45 min, mother–child cortisol levels were significantly inversely correlated. These findings contribute to theory and research on parent–child relationships by examining parenting behavior, developmental stage, and adrenocortical synchrony in tandem.     

Day-to-day friends’ victimization,aggression perpetration,and morning cortisol activity in late adolescents

This study investigates bidirectional associations between adolescents’ daily experiences of victimization and aggression perpetration within friendships. We investigated (a) across-day associations between victimization and aggression perpetration; (b) morning cortisol activity as a moderator of cross-day victimization and aggression links; and (c) potential sex differences in these patterns. For 4 consecutive days, 99 adolescents (M_age = 18.06, SD = 1.09, 46 females) reported whether they were victimized by or aggressive toward their friends. On three of these days, adolescents provided three morning saliva samples. Multilevel path analyses showed that across days, victimization and aggression were bidirectionally linked, but only for male adolescents. Additionally, for male adolescents, morning cortisol output (but not morning cortisol increase) moderated the association between victimization and next-day aggression; victimization predicted greater next-day aggression for boys with low, but not high, morning cortisol output. Findings implicate a physiological factor that may modify daily links between victimization and aggression in male adolescent friendships.     

Inhibition of antigen‐presenting cell function and stimulation of human peripheral blood mononuclear cells to express an antiinflammatory cytokine profile by the stress protein BiP: Relevance to the treatment of inflammatory arthritis

Objective

The stress protein and endoplasmic reticulum chaperone, immunoglobulin binding protein (BiP), is an autoantigen in rheumatoid arthritis (RA). Stress proteins, however, may have extracellular functions, mediated via cell surface receptors, that may include immunomodulatory functions. We sought to determine whether cell‐free BiP is present in the synovial fluid (SF) of patients with RA and to further investigate the possible extracellular antiinflammatory and immunomodulatory properties of BiP in peripheral blood mononuclear cells (PBMCs) in vitro.

Methods

The presence of BiP in SF was established by Western blotting. PBMCs were stimulated with exogenous recombinant human BiP, and cytokine production and cell proliferation were measured in the presence and absence of cell signaling inhibitors or neutralizing anti–interleukin‐10 (anti–IL‐10) monoclonal antibody. Cytokine levels were quantified by enzyme‐linked immunosorbent assay, cell proliferation by tritiated thymidine uptake, and cell surface molecule expression by flow cytometry.

Results

PBMCs responded to BiP with secretion of an antiinflammatory profile of cytokines. Although BiP stimulated the early production of tumor necrosis factor α (TNFα), the major cytokine induced was IL‐10. Soluble TNF receptor II and IL‐1 receptor antagonist secretion was also increased. Addition of SB203580, the MAPK p38 pathway inhibitor, partially inhibited the production of IL‐10 and TNFα, whereas they were unaffected by the MAPK ERK‐1/2 inhibitor PD98059. BiP also inhibited the recall antigen response by PBMCs to tuberculin purified protein derivative. Further investigation showed that incubation of monocytes in the presence of either BiP or IL‐10 down‐regulated CD86 and HLA–DR expression. The effect observed with IL‐10 was transient compared with the long‐lasting reduction induced by BiP.

Conclusion

Extracellular BiP may stimulate immunomodulatory and antiinflammatory pathways, which are only partly due to the production of IL‐10. These properties may be of relevance for the treatment of diseases such as RA.

     

Is there a role for glycosuria testing in sub-Saharan Africa?

BACKGROUND: With increasing urbanization and westernization, rates of diabetes in sub-Saharan Africa (sSA) are likely to rise. Early detection and intervention plays an important role in delaying development of complications. In sSA in particular there is need for an affordable, reliable, safe, feasible test to avert human suffering and exhausting already stressed health facilities. METHODS: Data from two large community-based studies were used to assess the value of glycosuria testing in the detection of diabetes in adults in a sub-Saharan country. A first study (A) tested participants for glycosuria by dipstick; if positive, fasting capillary glucose was measured. A later study (B) measured glucose concentration in venous blood 2 h after a 75-g glucose load; if glycaemia was > or = 10 mmol/l, urine was tested for glycosuria. RESULTS: The positive predictive value of glycosuria for a diagnosis of diabetes (fasting glucose > or = 6.7 mmol/l) was 48%. Sensitivity was 64% (57% if a 2-h-value > or = 10 mmol/l was used as gold standard). Sensitivity was higher among overweight and/or hypertensive subjects, among elderly people in the urban area, and among subjects with higher blood glucose levels. Extrapolated specificity was 99.7%, and the likelihood ratio 190. CONCLUSIONS: Glycosuria testing can identify a considerable number of undiagnosed diabetic patients when specially targeted at high-risk groups (obese, hypertensive, or elderly people). Dipstick glycosuria testing is an appropriate, safe, feasible test for sSA, where the prevalence of diabetes is expected to increase considerably in the near future.     

How community ART delivery may improve HIV treatment outcomes: Qualitative inquiry into mechanisms of effect in a randomized trial of community‐based ART initiation,monitoring and re‐supply (DO ART) in South Africa and Uganda

IntroductionUNAIDS fast track targets for ending the AIDS epidemic by 2030 call for viral suppression in 95% of people using antiretroviral therapy (ART) to treat HIV infection. Difficulties in linking to care following a positive HIV test have impeded progress towards meeting treatment targets. Community‐based HIV services may reduce linkage barriers and have been associated with high retention and favourable clinical outcomes. We use qualitative data from The Delivery Optimization of Antiretroviral Therapy (DO ART) Study, a three‐arm randomized trial of community ART initiation, monitoring and re‐supply conducted in western Uganda and KwaZulu‐Natal South Africa, to identify mechanisms through which community ART delivery may improve treatment outcomes, defined as viral suppression in people living with HIV (PLHIV).MethodsWe conducted open‐ended interviews with a purposeful sample of 150 DO ART participants across study arms and study sites, from October 2016 to November 2019. Interviews covered experiences of: (1) HIV testing; (2) initiating and refilling ART; and (3) participating in the DO ART Study. A combined inductive content analytic and thematic approach was used to characterize mechanisms through which community delivery of ART may have contributed to viral suppression in the DO ART trial.ResultsThe analysis yielded four potential mechanisms drawn from qualitative data representing the perspectives and priorities of DO ART participants. Empowering participants to schedule, re‐schedule and select the locations of community‐based visits via easy phone contact with clinical staff is characterized as flexibility. Integration refers to combining the components of clinic‐based visits into single interaction with a healthcare provider. Providers” willingness to talk at length with participants during visits, addressing non‐HIV as well as HIV‐related concerns, is termed “a slower pace”. Finally, increased efficiency denotes the time savings and increased income‐generating opportunities for participants brought about by delivering services in the community.ConclusionsUnderstanding the mechanisms through which HIV service delivery innovations produce an effect is key to transferability and potential scale‐up. The perspectives and priorities of PLHIV can indicate actionable changes for HIV care programs that may increase engagement in care and improve treatment outcomes.