We generated cortical interneurons (cINs) from iPSCs derived from14 healthy controls (HC cINs) and 14 patients with schizophrenia (SCZ cINs). Both HC cINs and SCZ cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo . However, SCZ cINs had dysregulated expression of protocadherin genes, which lie within documented SCZ loci. Mice lacking protocadherin α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. SCZ cINs similarly showed defects in synaptic density and arborization, which were reversed by inhibitors of Protein Kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in SCZ cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development.

Schizophrenia (SCZ) is a neurodevelopmental disorder. Thus, studying pathogenetic mechanisms underlying SCZ requires studying the development of brain cells. Cortical interneurons (cINs) are consistently observed to be abnormal in SCZ postmortem brains. These abnormalities may explain altered gamma oscillation and cognitive function in patients with SCZ. Of note, currently used antipsychotic drugs ameliorate psychosis, but they are not very effective in reversing cognitive deficits. Characterizing mechanisms of SCZ pathogenesis, especially related to cognitive deficits, may lead to improved treatments. We generated homogeneous populations of developing cINs from 15 healthy control (HC) iPSC lines and 15 SCZ iPSC lines. SCZ cINs, but not SCZ glutamatergic neurons, show dysregulated Oxidative Phosphorylation (OxPhos) related gene expression, accompanied by compromised mitochondrial function. The OxPhos deficit in cINs could be reversed by Alpha Lipoic Acid/Acetyl-L-Carnitine (ALA/ALC) but not by other chemicals previously identified as increasing mitochondrial function. The restoration of mitochondrial function by ALA/ALC was accompanied by a reversal of arborization deficits in SCZ cINs. OxPhos abnormality, even in the absence of any circuit environment with other neuronal subtypes, appears to be an intrinsic deficit in SCZ cINs.

Background: Men who have sex with men (MSM) have a high prevalence of anal and penile human papillomavirus (HPV) infections with MSM living with HIV (MSMLH) bearing the highest rates. Data on anogenital high-risk HPV (hrHPV) among MSM in Rwanda and the associated risk factors are scant. Methods: We recruited 350 self-identified MSM aged 18 years living in Kigali, Rwanda, with 300 recruited from the community and 50 from partner clinics. Anal and penile specimens from all participants were analyzed for hrHPV using the AmpFire platform. Logistic regression was used to calculate crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (95% CIs) as a measure of association between various factors and anal and penile hrHPV infection prevalence. Results: Anal hrHPV prevalence was 20.1%, was positively associated with having receptive anal sex with more partners (aOR: 9.21, 95% CI: 3.66 to 23.14), and was negatively associated with having insertive anal sex with more partners (aOR: 0.28, 95% CI: 0.12 to 0.66). Penile hrHPV prevalence was 35.0%, was negatively associated with having receptive anal sex with more partners (aOR: 0.29, 95% CI: 0.13 to 0.66), and differed significantly by HIV status, with 55.2% and 29.7% for MSMLH and HIV-negative MSM, respectively ( P < 0.01). Conclusion: Penile hrHPV prevalence was higher than that of anal hrHPV and it was significantly higher in Rwandan MSMLH than in HIV-negative MSM. The prevalence of anal and penile HPV infections is likely variable at different locations in Africa, according to a number of factors including HIV status and sexual practices.

Background Antiretroviral therapy (ART) success has led people to live longer with HIV/AIDS (PLWH) and thus be exposed to increasing risk of cardiovascular diseases (CVD). Hypertension (HTN), the biggest contributor to CVD burden, is a growing concern among PLWH. The current report describes the prevalence and predictors of HTN among PLWH in care in Cameroon. Methods This cross-sectional study included all PLWH aged 20 years and above who received care between 2016 and 2019 at one of the three Central Africa International Epidemiology Databases to Evaluate AIDS (CA-IeDEA) sites in Cameroon (Bamenda, Limbe, and Yaoundé). HTN was defined as blood pressure (BP) ≥140/90 mm Hg or self-reported use of antihypertensive medication. Logistic regressions models examined the relationship between HTN and clinical characteristics, and HIV-related factors. Results Among 9,839 eligible PLWH, 66.2% were women and 25.0% had prevalent HTN [age-standardized prevalence 23.9% (95% CI: 22.2–25.6)], among whom 28 (1.1%) were on BP lowering treatment, and 6 of those (21.4%) were at target BP levels. Median age (47.4 vs. 40.5 years), self-reported duration of HIV infection (5.1 vs 2.8 years years), duration of ART exposure (4.7 vs 2.3 years), and CD4 count (408 vs 359 cell/mm3) were higher in hypertensives than non-hypertensives (all p<0.001). Age and body mass index (BMI) were independently associated with higher prevalent HTN risk. PLWH starting ART had a 30% lower risk of prevalent HTN, but this advantage disappeared after a cumulative 2-year exposure to ART. There was no significant association between other HIV predictive characteristics and HTN. Conclusion About a quarter of these Cameroonian PLWH had HTN, driven among others by age and adiposity. Appropriate integration of HIV and NCDs services is needed to improve early detection, treatment and control of common comorbid NCD risk factors like hypertension and safeguard cardiovascular health in PLWH.

Objective Payers use consumer-directed health care to reduce costs by discouraging utilization of low-value services and encouraging use of low-cost providers. Low back pain (LBP) is a costly condition for which physical therapy is a high-value service. Factors predicting physical therapy utilization for LBP remain unclear, limiting the development of value-based initiatives. The purpose of this study was to identify important factors that impact the number of physical therapist visits per episode of care for US adults with nonspecific LBP. Methods This study was a retrospective observational cohort study of a clinical dataset derived from 80 clinics of a single physical therapy provider organization. Research variables were categorized at the individual (patient) level and the organization (therapist, clinic) level. A hierarchical regression model was designed to identify factors influencing the number of physical therapist visits per episode of care. Results Higher out-of-pocket payments per visit, receipt of “active” physical therapy, longer average visit length, earlier use of physical therapy, and sex of the therapist (male) were found to predict fewer visits per episode of care. Percent change of function, prior receipt of physical therapy by the same provider organization, self-discharge from physical therapy, level of starting function, and therapist certification were found to predict more visits. Of the variance in number of visits, 8.0% is attributable to the health care organization. Conclusions Individual factors, such as higher out-of-pocket payment, have a significant impact on reducing visits per episode of care and should be considered when developing value-based initiatives to optimize clinical and utilization outcomes.