The effect of pyridostigmine on small intestinal bacterial overgrowth (SIBO) and plasma inflammatory biomarkers in HIV-associated autonomic neuropathies.

Small intestinal bacterial overgrowth (SIBO) is common among patients with HIV-associated autonomic neuropathies (HIV-AN) and may be associated with increased bacterial translocation and elevated plasma inflammatory biomarkers. Pyridostigmine is an acetylcholinesterase inhibitor which has been used to augment autonomic signaling. We sought preliminary evidence as to whether pyridostigmine could improve proximal gastrointestinal motility, reduce SIBO, reduce plasma sCD14 (a marker of macrophage activation and indirect measure of translocation), and reduce the inflammatory cytokines IL-6 and TNFα in patients with HIV-AN. Fifteen participants with well-controlled HIV, HIV-AN, and SIBO were treated with 8 weeks of pyridostigmine (30 mg PO TID). Glucose breath testing for SIBO, gastric emptying studies (GES) to assess motility, plasma sCD14, IL-6, and TNFα, and gastrointestinal autonomic symptoms were compared before and after treatment. Thirteen participants (87%) experienced an improvement in SIBO following pyridostigmine treatment; with an average improvement of 50% (p = 0.016). There was no change in gastrointestinal motility; however, only two participants met GES criteria for gastroparesis at baseline. TNFα and sCD14 levels declined by 12% (p = 0.004) and 19% (p = 0.015), respectively; there was no significant change in IL-6 or gastrointestinal symptoms. Pyridostigmine may ameliorate SIBO and reduce levels of sCD14 and TNFα in patients with HIV-AN. Larger placebo-controlled studies are needed to definitively delineate how HIV-AN affects gastrointestinal motility, SIBO, and systemic inflammation in HIV, and whether treatment improves clinical outcomes.

Undue burden: Black faculty, COVID-19, and the racial justice movement.

A crucial reckoning was initiated when the COVID-19 pandemic began to expose and intensify long-standing racial/ethnic health inequities, all while various sectors of society pursued racial justice reform. As a result, there has been a contextual shift towards broader recognition of systemic racism, and not race, as the shared foundational driver of both societal maladies. This confluence of issues is of particular relevance to Black populations disproportionately affected by the pandemic and racial injustice. In response, institutions have initiated diversity, equity, and inclusion (DEI) efforts as a way forward. This article considers how the dual pandemic climate of COVID-19-related health inequities and the racial justice movement could exacerbate the "time and effort tax" on Black faculty to engage in DEI efforts in academia and biomedicine. We discuss the impact of this "tax" on career advancement and well-being, and introduce an operational framework for considering the interconnected influence of systemic racism, the dual pandemics, and DEI work on the experience of Black faculty. If not meaningfully addressed, the "time and effort tax" could contribute to Black and other underrepresented minority faculty leaving academia and biomedicine - consequently, the very diversity, equity, and inclusion work meant to increase representation could decrease it.

Sympathetic function and markers of inflammation in well-controlled HIV.

PURPOSE: HIV-associated autonomic neuropathy (HIV-AN) is common and may be associated with both sympathetic and parasympathetic dysfunction. Sympathetic nervous system (SNS) dysfunction occurs on a continuum of hyper-to hypo-adrenergic function, and may be a mediator between psychological stress and chronic inflammation. We sought to describe patterns of SNS dysfunction in people living with HIV, and to determine whether SNS dysfunction is associated with markers of systemic inflammation (focusing on IL-6 and TNF-α) and pain and anxiety. METHODS: Forty-seven people with well-controlled HIV and without confounding medical conditions or medications completed the Medical Outcomes Survey (MOS-HIV), quantification of a panel of 41 plasma cytokines/chemokines, and a standardized, non-invasive autonomic reflex screen (ARS). Adrenergic baroreflex sensitivity (BRSA) was calculated from the ARS as a measure of SNS function. RESULTS: Pain (46%) and anxiety (52%) were commonly reported on the MOS-HIV. BRSA was reduced in 30% of participants and elevated in 9% with the latter occurring only in participants with normal to mild HIV-AN. BRSA was significantly associated with IL-6, but not with TNF-α, pain or anxiety. Exploratory analyses also revealed positive associations of BRSA with numerous other cytokines with no significant inverse associations. CONCLUSION: Higher BRSA, indicative of a more hyperadrenergic state, can be part of the spectrum of early HIV-AN, and may be associated with elevations in multiple cytokines including IL-6. These associations do not appear to be driven by stressors such as pain or anxiety.