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Coprevalence and Associations of Diabetes Mellitus and Hypertension Among People Living With HIV/AIDS in Cameroon
Background: The association between HIV infection and increased cardiometabolic risk, attributed to chronic inflammation in people living with HIV (PLWH) and/or antiretroviral therapy (ART) effects, has been inconsistent. In this study, we aimed to assess the associations of HIV-related factors with hypertension (HTN) and type-2 diabetes mellitus (T2DM), and the potential mediation effects of body mass index (BMI) in the associations between ART use and HTN or T2DM in PLWH in Cameroon. Methods: A cross-sectional study was conducted with 14,119 adult PLWH from Cameroon enrolled in the International epidemiology Databases to Evaluate AIDS (IeDEA) between 2016 and 2021. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg and/or current use of antihypertensive medication, while T2DM was defined as fasting blood sugar ≥ 126 mg/dL and/or use of antidiabetic medications. Univariable and multivariable multinomial logistic regression analyses examined the associations of factors with HTN alone, T2DM alone, and both (HTN + T2DM). Mediation analyses were conducted to assess the potential mediation roles of BMI, while controlling for age, sex, and smoking. Results: Of the 14,119 participants, 9177 (65%) were women, with a median age of 42 (25th–75th percentiles: 35–51) years. Age \u3e 50 years was associated with HTN alone, T2DM alone, and HTN + T2DM compared to the age group 19–29 years. Men had higher odds of having HTN + T2DM. Overweight and obesity were predictors of HTN alone compared to being underweight. WHO stages II and III HIV disease were inversely associated with HTN alone compared to stage I. The odds of diabetes alone were lower with ART use. BMI partially mediated the association between ART use and hypertension, with a proportion of mediation effect of 49.6% (all p \u3c 0.02). However, BMI did not mediate the relationship between ART use and diabetes. Conclusions: Traditional cardiovascular risk factors were strongly associated with hypertension among PLWH, while HIV-related exposures had smaller associations. BMI partially mediated the association between ART use and hypertension. This study emphasizes the importance of screening, monitoring, and managing HTN and T2DM in older, male, and overweight/obese PLWH. Further research on the associations of HIV disease stage and ART use with HTN and T2DM is warranted
A Comparison of 467 Uroflowmetry Results in Repaired Hypospadias vs. Normal Male Flows
Introduction: There are currently no clinical criteria for obstructed urinary flow after hypospadias repair surgery. Previous studies have utilized adult and pediatric nomograms and flow shapes to define obstruction, however these methods are limited by a lack of standardization and lack of interrater reliability when determining flow shapes, respectively. The idealized voider derived flow indexes offer a way to track uroflowmetry results in a volume and age agnostic manner. Objective: We sought to evaluate all our hypospadias patients over a 10-year period and identify patients without complications and those with complications and determine their respective flow parameters. Our secondary objective is to identify which uroflowmetry parameters are the most significant predictors of urethral stricture and meatal stenosis at the time of the uroflowmetry study. Study design: Retrospective chart review was used to compile demographic information, details of hypospadias repair surgeries, and uroflowmetry results from pediatric hypospadias repair patients. Subjects were divided into distal, midshaft, and proximal groups based on the initial location of their urethral meatus. Flows from the hypospadias repair groups were compared to flows from normal age matched controls from a previous study. We compared flows from hypospadias repair patients with no complications present with those who had urethral stricture or meatal stenosis present at the time of uroflowmetry. Binary logistic regression and ROC analysis was used to assess different uroflowmetry parameters’ ability to detect the presence of obstructed urine flow. Results: 467 uroflowmetry studies from 200 hypospadias repair patients were included in the database. Compared to controls, the hypospadias repair groups tended to have significantly lower Qmax, Qavg, Qmax FI, Qavg FI, and longer ttQmax. Significant differences in flow parameters were observed when comparing hypospadias repair patients with and without flow obstructing complications at the time of uroflowmetry. Binary logistic regression including various uroflowmetry parameters showed Qmax FI had a significant effect on the odds of observing the absence of a stricture in proximal and distal hypospadias cases. Discussion: Of the uroflowmetry parameters analyzed, binary logistic regression and the likelihood ratio of a positive result all point to Qmax FI as the better parameter to use to detect the presence of complications in patients who have undergone distal or proximal hypospadias repair surgery. Conclusion: We have established normal parameters for post-operative hypospadias repair patients which can be used to follow patients over time and allow for the identification of complications by keeping track of flow indexes which are volume and age agnostic
Point-Of-Care Ultrasound to Assess Diaphragmatic Paralysis in Resource-Limited Setting: A Case Series
Diaphragmatic dysfunction can arise from various factors, and Guillain–Barre syndrome, characterized by acute inflam-matory polyradiculoneuropathy, is one such cause that may result in respiratory failure due to diaphragmatic paralysis. Prompt recognition and timely intervention, including airway protection and addressing the underlying pathology, are crucial for achieving optimal patient outcomes. Point-of-care ultrasound, specifically utilizing the M-mode function, can be employed for individuals displaying symptoms of diaphragmatic paralysis. This diagnostic approach is uncomplicated an effective tool for serial follow-up. In this context, we present a case series involving three patients with diaphragmatic paralysis in a limited-resource setting
Neuronal Panx1 Drives Peripheral Sensitization in Experimental Plantar Inflammatory Pain
Background: The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. Methods: Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and β-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. β-galactosidase (β-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice. Results: Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P \u3c 0.01 vs. WT group), indicating that Panx1 was positively correlated with pain sensitivity. In Neuro2a, global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group (P \u3c 0.05), revealing that Panx1 enhanced neurogenesis and excitability. Similarly, global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor (NGF) treatment (P \u3c 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P \u3c 0.01 vs. Panx1 KO group). Furthermore, ATP release increased Ca2+ responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment (P \u3c 0.01 vs. Panx1 KO group), suggesting that Panx1 in glia also impacts exaggerated neuronal excitability. Interestingly, neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs, as evidenced by stunted neurite outgrowth (P \u3c 0.05 vs. Panx1 KO group; P \u3c 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/β-catenin signaling (P \u3c 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P \u3c 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P \u3c 0.01 vs. WT group). Analysis of β-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher (2.5-fold increase) in the DRG than in the TG. Conclusions: The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability. This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain, where similar studies revealed a prominent role for glial Panx1. The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models
Dysregulated Expression Patterns of Circular Rnas in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential
Circular RNAs (circRNAs) are stable, enclosed, non-coding RNA molecules with dynamic regulatory propensity. Their biogenesis involves a back-splicing process, forming a highly stable and operational RNA molecule. Dysregulated circRNA expression can drive carcinogenic and tumorigenic transformation through the orchestration of epigenetic modifications via extensive RNA and protein-binding domains. These multi-ranged functional capabilities have unveiled extensive identification of previously unknown molecular and cellular patterns of cancer cells. Reliable circRNA expression patterns can aid in early disease detection and provide criteria for genome-specific personalized medicine. Studies described in this review have revealed the novelty of circRNAs and their biological ss as prognostic and diagnostic biomarkers
Higher Level of Physical Activity Reduces Mental and Neurological Symptoms During and Two Years After COVID-19 Infection in Young Women
Previous studies found that regular physical activity (PA) can lower the risk of SARS-CoV-2 (COVID-19) infection and post-COVID-19 condition (PCC), yet its specific effects in young women have not yet been investigated. Thus, we aimed to examine whether regular physical activity reduces the number of symptoms during and after COVID-19 infection among young women aged between 18 and 34 (N = 802), in which the confounding effect of other morbidities could be excluded. The average time since infection was 23.5 months. Participants were classified into low, moderate, and high PA categories based on the reported minutes per week of moderate and vigorous PA. Using the Post-COVID-19 Case Report Form, 50 different symptoms were assessed. Although regular PA did not decrease the prevalence of COVID-19 infection and PCC but significantly reduced the number of mental and neurological symptoms both in acute COVID-19 and PCC. Importantly, the high level of PA had a greater impact on health improvements. In addition, the rate of reinfection decreased with an increased level of PA. In conclusion, a higher level of regular PA can reduce the risk of reinfection and the number of mental and neurological symptoms in PCC underlying the importance of regular PA, even in this and likely other viral disease conditions
Relationship Between FEV1/FVC and Age in Children With Asthma
Introduction: Forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) normally decreases through childhood, increases briefly during early adolescence, and then declines throughout life. The physiology behind this temporary increase during early adolescence is not well understood. The objective of this study was to determine if this pattern occurs in children with asthma. Design: Single-center, cross-sectional, retrospective analysis of pulmonary function tests obtained over a 5-year period in children 5–18 years of age with persistent asthma. Results: A total of 1793 patients satisfied all inclusion and exclusion criteria. The mean age (±SD) was 10.4 ± 3.8 years. Forty-eight percent were female. Mean FEV1/FVC was 0.83 ± 0.09. FEV1/FVC was lower at 5 years of age than in healthy children, declined from age 5 to 11 by 5.7% compared to 7.3% in healthy girls, and 5.8% compared to 9.4% in healthy boys. FEV1/FVC increased in early adolescence, but at age 16, was 5.6% lower in male children compared to healthy children, and 5.4% lower in females. The ratio was lower in obese children at all ages but demonstrated the same curvilinear shape as healthy children. In absolute terms, FEV1 grew proportionately more than FVC during early adolescence, so the ratio of FEV1/FVC increased during that period. The curvilinear shape of the curve remained in postbronchodilator testing, though significantly blunted. Conclusions: FEV1/FVC is lower in children with persistent asthma than healthy children, but the “Shepherd\u27s Hook” pattern is preserved. This was true in obese patients with asthma, although their FEV1/FVC ratios were lower throughout all stages of childhood and adolescence
Frailty-Related Factors Among Women Living With and Without HIV Aged 40 Years and Older. the Women’s Interagency HIV Study
Background: Frailty is a clinical, geriatric syndrome linked to disability and mortality; and may be associated with a variety of factors among underrepresented and underserved women living with HIV (WLWH) and without HIV (WLWOH) transitioning through the adult life course. Objectives: Determine whether a published set of factors associated cross-sectionally with frailty in WLWH and similar WLWOH at average age 39 years in 2005/2006 were associated with frailty in 2018/2019 among women who initiated frailty assessments at age ≥40 years, or whether a new set of factors were associated with frailty. Design: Cross-sectional analyses within a longitudinal cohort study. Setting: The multi-center Women’s Interagency HIV Study (WIHS). Participants: 1285 participants (951 WLWH, 334 WLWOH), median age 53 years (interquartile range 47–58 years). Measurements: The Fried Frailty Phenotype (FFP) in association with 23 factors representing HIV serostatus, other infections, sociodemographic factors, health behaviors, and chronic diseases. Results: Frailty prevalence was 11.1% in 2018/2019 (12.6% among WLWOH, 9.6% among WLWH, p=0.121). The published 2005/2006 final multivariable stepwise regression model contained 9 predictors of frailty. When refit to women in 2018/2019, only age ≥50 years and annual income ≤12,000, obesity (body mass index (BMI) ≥30kg/m2), and history of tuberculosis and cancer. Conclusion: Different chronic and infectious disease factors were associated with frailty among WLWH and WLWOH over the adult life course. Understanding factors associated with frailty by adult life stage, allows identification and implementation of novel, temporal interventions to alleviate frailty-associated outcomes and enhance quality of life among WLWH and WLWOH