Reducing sexual risk and promoting acceptance of men who have sex with men living with HIV in India: Outcomes and process evaluation of a pilot randomised multi-level intervention

ABSTRACT

HIV-positive men who have sex with men (HIV+MSM) in India need culturally-relevant interventions to promote safer sex. We tested a multi-level intervention among HIV+MSM that targeted individual, interpersonal, and community factors, based on the Social-Personal and Social Ecological Models. We conducted a 2?×?2 factorial RCT with 119 HIV+MSM randomised to receive either an individual-level intervention (ILI) using motivational interviewing to promote safer sex, a community-level intervention (CLI) to strengthen community norms toward safer sex and reduce stigma among MSM communities, a multi-level intervention combining the individual- and community-level interventions (ILI?+?CLI), or standard-of-care control. Participants completed pre- and post-intervention assessments of a composite sexual risk score and a process evaluation to assess fidelity and satisfaction. Out of the 119 HIV+MSM, 106 (89.0%) completed pre- and post-intervention assessments. Generalised Estimating Equation models showed that both CLI (Incidence Rate Ratio [IRR]?=?.67, 95% CI .47 to .96) and ILI?+?CLI (IRR?=?.66, 95% CI .48 to .91) groups had a statistically significant decrease in sexual risk compared to the standard-of-care. The interventions had high levels of fidelity and satisfaction. This pilot RCT demonstrated feasibility and potential effectiveness of a multi-level intervention that addresses individual, interpersonal and community-level contributors of sexual risk among HIV+MSM.     

Nicotine smoking concentrations modulate GABAergic synaptic transmission in murine medial prefrontal cortex by activation of α7* and β2* nicotinic receptors

Nicotine is the major addictive component of cigarettes, reaching a brain concentration of ~300 nM during smoking of a single cigarette. The prefrontal cortex (PFC) mechanisms underlying temporary changes of working memory during smoking are incompletely understood. Here, we investigated whether 300 nM nicotine modulates γ‐aminobutyric acid (GABA) ergic synaptic transmission from pyramidal neurons of the output layer (V) of the murine medial PFC. We used patch clamp in vitro recording from C57BL/6 mice in the whole‐cell configuration to investigate the effect of nicotine on pharmacologically isolated GABAergic postsynaptic currents (IPSCs) in the absence or presence of methyllycaconitine (MLA) or dihydro‐β‐erythroidine (DHβE), selective antagonists of α7‐ and β2‐containing (α7* and β2*) nicotinic acetylcholine receptors (AChRs), respectively. Our results indicated that nicotine, alone or in the presence of MLA, decreases electrically evoked IPSC (eIPSC) amplitude, whereas in the presence of DHβE, nicotine elicited either an eIPSCs amplitude increase or a decrease. In the presence of DHβE, nicotine increased membrane conductance leaving the paired pulse ratio unchanged in all conditions, suggesting a non‐β2* mediated effect. In the presence of MLA, nicotine decreased the mean spontaneous IPSC (sIPSC) frequency but increased their rise time, suggesting a non‐α7* AChR‐mediated synaptic modulation. Also, in the presence of DHβE, nicotine decreased both eIPSC rise and decay times. No receptors other than α7* and β2* appear to be involved in the nicotine effect. Our results indicate that nicotine smoking concentrations modulate GABAergic synaptic currents through mixed pre‐ and post‐synaptic mechanisms by activation of α7* and β2* AChRs.     

Dopamine modulates the optomotor response to unreliable visual stimuli in Drosophila melanogaster

State‐dependent modulation of sensory systems has been studied in many organisms and is possibly mediated through neuromodulators such as monoamine neurotransmitters. Among these, dopamine is involved in many aspects of animal behaviour, including movement control, attention, motivation and cognition. However, the precise neural mechanism underlying dopaminergic modulation of behaviour induced by sensory stimuli remains poorly understood. Here, we used Drosophila melanogaster to show that dopamine can modulate the optomotor response to moving visual stimuli including noise. The optomotor response is the head‐turning response to moving objects, which is observed in most sight‐reliant animals including mammals and insects. First, the effects of the dopamine system on the optomotor response were investigated in mutant flies deficient in dopamine receptors D1R1 or D1R2, which are involved in the modulation of sleep‐arousal in flies. We examined the optomotor response in D1R1 knockout (D1R1 KO) and D1R2 knockout (D1R2 KO) flies and found that it was not affected in D1R1 KO flies; however, it was significantly reduced in D1R2 KO flies compared with the wild type. Using cell‐type‐specific expression of an RNA interference construct of D1R2, we identified the fan‐shaped body, a part of the central complex, responsible for dopamine‐mediated modulation of the optomotor response. In particular, pontine cells in the fan‐shaped body seemed important in the modulation of the optomotor response, and their neural activity was required for the optomotor response. These results suggest a novel role of the central complex in the modulation of a behaviour based on the processing of sensory stimulations.     

COVID-19, SARS and MERS: A neurological perspective

Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS-CoV, MERS-CoV and SARS-CoV-2. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS, and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.     

IVIG in childhood primary angiitis of the central nervous system: A case report

Aggressive immunosuppressive therapies have been proposed to treat primary angiitis of the central nervous system (PACNS). Here, we report the first successfully stabilized case of childhood, small-vessel PACNS with intravenous immunoglobulin (IVIG) therapy.A 12-year-old boy was admitted to our hospital complaining of recurrent headaches and upper-left homonymous quadrantanopia, since the age of 11 years. Brain computed tomography scans revealed fine calcification in the right temporal and occipital lobes. Brain magnetic resonance imaging scans revealed white matter lesions, with gadolinium enhancement, which waxed, waned, and migrated for 1 year, without immunomodulatory therapies. A cerebrospinal fluid study showed pleocytosis (12 cells per µl). No clinical or serological findings suggested systemic inflammation or vasculitis. Brain angiography was unremarkable. Brain biopsy revealed thickened and hyalinized small vessels, with intramural infiltration of inflammatory cells, which confirmed the diagnosis of small-vessel PACNS. Because the patient developed surgical site infection following biopsy, the administration of monthly IVIG (2 g/kg) was prescribed, instead of immunosuppressive agents. After IVIG therapy, the patient remained stable, except for a single episode of mild radiological exacerbation at 16 months, which occurred when the IVIG interval was expanded. Oral prednisone was added and gradually tapered. At 50 months, his intellectual abilities and motor functions were normal, although he showed residual upper-left homonymous quadrantanopia and post-exercise headache. A temporary headache, associated with the immunoglobulin infusion, was resolved by slowing the infusion rate. PACNS should be treated aggressively to improve prognosis. However, when immunosuppressants are contraindicated, IVIG may be an alternative therapeutic option.     

Relationship between early‐life nutrition and ages at menarche and first pregnancy,and childbirth rates of young adults: Evidence from APCAPS in India

India's Integrated Child Development Services (ICDS) provides daily supplementary nutrition and other public health services to women and children. We estimated associations between exposure to early‐childhood ICDS nutrition and adult reproductive outcomes. During 1987–1990, a balanced protein–calorie supplement called “upma”—made from locally available corn–soya ingredients—was rolled out by subdistricts near Hyderabad and offered to pregnant women and children under age 6 years. In a controlled trial, 15 villages received the supplement and 14 did not. We used data from a 2010–2012 resurvey of adults born during the trial (n = 715 in intervention and n = 645 in control arms). We used propensity score matching methods to estimate the associations between birth in an intervention village and menarcheal age, age at first pregnancy, and fertility of adults. We found that women born in the intervention group during the trial, as compared with the control group, had menarche 0.45 (95% confidence interval [CI: 0.22, 0.68]; p < .001) years later and first pregnancy 0.53 (95% CI [0.04, 1.02]; p < .05) years later. Married women from the intervention group had menarche 0.36 (95% CI [0.09, 0.64]; p < .01) years later, first cohabitation with partner 0.8 (95% CI [0.27, 1.33]; p < .01) years later, and first pregnancy 0.53 (95% CI [0.04, 1.02]; p < .05) years later than married women in the control group. There was no significant difference between intervention and control group women regarding whether they had at least one childbirth or the total number of children born. The findings were similar when we employed inverse propensity score weighted regression models.