Amanda J. Miller

Background: In South Africa, pregnant and lactating women (PLW) face a dual burden of high alcohol use and HIV prevalence, both of which adversely affect maternal and infant health. However, few interventions address alcohol use and HIV risk concurrently in this population. Objective: This study seeks to adapt and pilot-test in a randomized controlled trial (RCT) the peer-led multisession intervention Mentor Mothers Plus (MM+) to integrate alcohol reduction strategies with HIV prevention and care support (in a seroneutral intervention) among PLW in Saldanha Bay, Western Cape, South Africa. Methods: Using the ADAPT-ITT (assessment, decision, adaptation, production, topical experts, integration, training, testing) framework, we adapted the evidence-based Mentor Mother (MM) model, originally aimed at reducing vertical HIV transmission among mothers with HIV. Our mixed methods design includes (1) qualitative research, including in-depth interviews (IDIs) and focus group discussions (FGDs), to assess drivers of perinatal alcohol use and HIV risk; (2) intervention adaptation through community-based participatory workshops with stakeholders to refine the MM+ intervention in order to include culturally and contextually strategies; and (3) a pilot RCT with 100 pregnant women (≥16 years old, reporting recent alcohol use) randomized in a 1:1 ratio to the MM+ intervention (motivational interviewing [MI], including HIV and alcohol reduction messaging) or enhanced standard of care (SOC). Primary RCT outcomes include reduced alcohol use, via phosphatidylethanol (PEth) blood levels at 6-month follow-up. Secondary outcomes include uptake and adherence to pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) among women with HIV, as well as intervention fidelity, feasibility, and acceptability. Results: Community research included 2 FGDs with health workers (n=6) and community leaders (n=7) and 31 interviews with partners and peers of PLW. Data showed that women are motivated to reduce alcohol use for child health but face barriers (eg, misconceptions about safety of alcohol use, poverty, trauma, and intimate partner violence [IPV]). Alcohol use is with friends/family members/partners and tied to financial stress, unplanned pregnancy, and poor mental health. MM+ support preferences emphasize nonjudgmental, peer-based mentorship, family involvement, and faith/community engagement. Gaps include stigma around HIV and contraceptive services. Communities recommend mentor mothers with lived experience, providing culturally relevant, empathetic support, and linking to social and clinical services. In August 2025, a community workshop refined the intervention, emphasizing the need for trustworthy mentor mothers with lived experience. Priorities included culturally relevant information on alcohol use, HIV prevention, family planning, trauma and interpersonal violence support, and flexible delivery. Next steps involve finalizing materials, training mentor mothers, and launching the RCT. Conclusions: Our community-based, participatory study, MM+, offers a promising approach to address co-occurring alcohol use and HIV among PLW. Stakeholder engagement enhances contextual relevance and supports future scalability. The RCT will evaluate efficacy of the model in reducing alcohol and improving HIV outcomes. Trial Registration: Clinicaltrials.gov NCT06962592; https://clinicaltrials.gov/study/NCT06962592 International Registered Report Identifier (IRRID): DERR1-10.2196/78856

BACKGROUND In South Africa, pregnant and lactating women (PLW) face a dual burden of high alcohol use and HIV prevalence, both of which adversely affect maternal and infant health. However, few interventions address alcohol use and HIV risk concurrently in this population. OBJECTIVE This study seeks to adapt and pilot-test in a randomized controlled trial (RCT) the peer-led multisession intervention Mentor Mothers Plus (MM+) to integrate alcohol reduction strategies with HIV prevention and care support (in a seroneutral intervention) among PLW in Saldanha Bay, Western Cape, South Africa. METHODS Using the ADAPT-ITT (assessment, decision, adaptation, production, topical experts, integration, training, testing) framework, we adapted the evidence-based Mentor Mother (MM) model, originally aimed at reducing vertical HIV transmission among mothers with HIV. Our mixed methods design includes (1) qualitative research, including in-depth interviews (IDIs) and focus group discussions (FGDs), to assess drivers of perinatal alcohol use and HIV risk; (2) intervention adaptation through community-based participatory workshops with stakeholders to refine the MM+ intervention in order to include culturally and contextually strategies; and (3) a pilot RCT with 100 pregnant women (≥16 years old, reporting recent alcohol use) randomized in a 1:1 ratio to the MM+ intervention (motivational interviewing [MI], including HIV and alcohol reduction messaging) or enhanced standard of care (SOC). Primary RCT outcomes include reduced alcohol use, via phosphatidylethanol (PEth) blood levels at 6-month follow-up. Secondary outcomes include uptake and adherence to pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) among women with HIV, as well as intervention fidelity, feasibility, and acceptability. RESULTS Community research included 2 FGDs with health workers (n=6) and community leaders (n=7) and 31 interviews with partners and peers of PLW. Data showed that women are motivated to reduce alcohol use for child health but face barriers (eg, misconceptions about safety of alcohol use, poverty, trauma, and intimate partner violence [IPV]). Alcohol use is with friends/family members/partners and tied to financial stress, unplanned pregnancy, and poor mental health. MM+ support preferences emphasize nonjudgmental, peer-based mentorship, family involvement, and faith/community engagement. Gaps include stigma around HIV and contraceptive services. Communities recommend mentor mothers with lived experience, providing culturally relevant, empathetic support, and linking to social and clinical services. In August 2025, a community workshop refined the intervention, emphasizing the need for trustworthy mentor mothers with lived experience. Priorities included culturally relevant information on alcohol use, HIV prevention, family planning, trauma and interpersonal violence support, and flexible delivery. Next steps involve finalizing materials, training mentor mothers, and launching the RCT. CONCLUSIONS Our community-based, participatory study, MM+, offers a promising approach to address co-occurring alcohol use and HIV among PLW. Stakeholder engagement enhances contextual relevance and supports future scalability. The RCT will evaluate efficacy of the model in reducing alcohol and improving HIV outcomes. CLINICALTRIAL Clinicaltrials.gov NCT06962592; https://clinicaltrials.gov/study/NCT06962592 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/78856

Cerebral blood flow (CBF) is vital for delivering oxygen and nutrients to the brain. Many forms of orthostatic intolerance (OI) involve impaired regulation of CBF in the upright posture, which results in disabling symptoms that decrease quality of life. Because CBF is not easy to measure, rises in heart rate or drops in blood pressure are used as proxies for abnormal CBF. These result in diagnoses such as postural orthostatic tachycardia syndrome and orthostatic hypotension. However, in many other OI syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and long COVID, heart rate and blood pressure are frequently normal despite significant drops in CBF. This often leads to the incorrect conclusion that there is nothing hemodynamically abnormal in these patients and thus no explanation or treatment is needed. There is a need to measure CBF, as orthostatic hypoperfusion is the shared pathophysiology for all forms of OI. In this review, we examine the literature studying CBF dysfunction in various syndromes with OI and evaluate methods of measuring CBF including transcranial Doppler ultrasound, extracranial cerebral blood flow ultrasound, near infrared spectroscopy, and wearable devices.

In healthy young adults, increased sympathetic activation induced by lower body negative pressure, led to a decrease in renal cortical and medullary oxygenation measured by T2*, a noninvasive magnetic resonance derived index of deoxyhemoglobin levels. In this study, we observed a significant decrease in renal cortical and medullary oxygenation with LBNP as well as an increase in renal vasoconstriction. We speculate that sympathetic renal vasoconstriction led to a significant reduction in tissue oxygenation by limiting oxygen delivery to the renal medulla.

Angiotensin (Ang)-(1-7) is a beneficial renin–angiotensin system (RAS) hormone that elicits protective cardiometabolic effects in young animal models of hypertension, obesity, and metabolic syndrome. The impact of Ang-(1-7) on cardiovascular and metabolic outcomes during aging, however, remains unexplored. This study tested the hypothesis that Ang-(1-7) attenuates age-related elevations in blood pressure and insulin resistance in mice. Young adult (two-month-old) and aged (16-month-old) male C57BL/6J mice received Ang-(1-7) (400 ng/kg/min) or saline for six-weeks via a subcutaneous osmotic mini-pump. Arterial blood pressure and metabolic function indices (body composition, insulin sensitivity, and glucose tolerance) were measured at the end of treatment. Adipose and cardiac tissue masses and cardiac RAS, sympathetic and inflammatory marker gene expression were also measured. We found that chronic Ang-(1-7) treatment decreased systolic and mean blood pressure, with a similar trend for diastolic blood pressure. Ang-(1-7) also improved insulin sensitivity in aged mice to levels in young mice, without effects on glucose tolerance or body composition. The blood pressure–lowering effects of Ang-(1-7) in aged mice were associated with reduced sympathetic outflow to the heart. These findings suggest Ang-(1-7) may provide a novel pharmacological target to improve age-related cardiometabolic risk.

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2–12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation ([ ]) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, [ ] of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO₂ response during exercise in patients with PAD. NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

Ehlers-Danlos Syndromes (EDS) are a group of heritable disorders of connective tissue (HDCT) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Orthostatic intolerance (OI) is highly prevalent in EDS however mechanisms linking OI to EDS remain poorly understood. We hypothesize that impaired blood pressure (BP) and heart rate control is associated with lower arterial stiffness in people with EDS. Orthostatic vital signs and arterial stiffness were assessed in a cohort of 60 people with EDS (49 female, 36 ± 16 years). Arterial elasticity was assessed by central and peripheral pulse wave velocity (PWV). Central PWV was lower in people with EDS compared to reference values in healthy subjects. In participants with EDS, central PWV was correlated to supine systolic BP (r = 0.387, p = 0.002), supine diastolic BP (r = 0.400, p = 0.002), and seated systolic BP (r = 0.399, p = 0.002). There were no significant correlations between PWV and changes in BP or heart rate with standing (p > 0.05). Between EDS types, there were no differences in supine hemodynamics or PWV measures (p > 0.05). These data demonstrate that increased arterial elasticity is associated with lower BP in people with EDS which may contribute to orthostatic symptoms and potentially provides a quantitative clinical measure for future genotype-phenotype investigations.