Relational solidarity and COVID-19: an ethical approach to disrupt the global health disparity pathway.

While the effects of COVID-19 are being felt globally, the pandemic disproportionately affects lower- and middle-income countries (LMICs) by exacerbating existing global health disparities. In this article, we illustrate how intersecting upstream social determinants of global health form a disparity pathway that compromises LMICs' ability to respond to the pandemic. We consider pre-existing disease burden and baseline susceptibility, limited disease prevention resources, and unequal access to basic and specialized health care, essential drugs, and clinical trials. Recognizing that ongoing and underlying disparity issues will require long-term correction efforts, this pathway approach is nonetheless helpful to inform ethical responses to this global pandemic. It can facilitate international cooperation during the pandemic to reduce the disparate burdens among different regions without imposing significant burden on any particular contributor. The pathway approach allows international stakeholders in various social positions to respond to different components of the pathway based on their respective strengths and resources to help break the cycle of global health inequity. Guided by the ethical principles of relational and pragmatic solidarity, we argue for a coordinated global division of labor such that different stakeholders can collaborate to foster equitable healthcare access during this pandemic.

Multi-parametric analysis of 57 SYNGAP1 variants reveal impacts on GTPase signaling, localization, and protein stability.

SYNGAP1 is a neuronal Ras and Rap GTPase-activating protein with important roles in regulating excitatory synaptic plasticity. While many SYNGAP1 missense and nonsense mutations have been associated with intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder (ASD), whether and how they contribute to individual disease phenotypes is often unknown. Here, we characterize 57 variants in seven assays that examine multiple aspects of SYNGAP1 function. Specifically, we used multiplex phospho-flow cytometry to measure variant impact on protein stability, pERK, pGSK3ß, pp38, pCREB, and high-content imaging to examine subcellular localization. We find variants ranging from complete loss-of-function (LoF) to wild-type (WT)-like in their regulation of pERK and pGSK3ß, while all variants retain at least partial ability to dephosphorylate pCREB. Interestingly, our assays reveal that a larger proportion of variants located within the disordered domain of unknown function (DUF) comprising the C-terminal half of SYNGAP1 exhibited higher LoF, compared to variants within the better studied catalytic domain. Moreover, we find protein instability to be a major contributor to dysfunction for only two missense variants, both located within the catalytic domain. Using high-content imaging, we find variants located within the C2 domain known to mediate membrane lipid interactions exhibit significantly larger cytoplasmic speckles than WT SYNGAP1. Moreover, this subcellular phenotype shows both correlation with altered catalytic activity and unique deviation from signaling assay results, highlighting multiple independent molecular mechanisms underlying variant dysfunction. Our multidimensional dataset allows clustering of variants based on functional phenotypes and provides high-confidence, multi-functional measures for making pathogenicity predictions.

Global Disparity and Solidarity in a Pandemic.

While the domestic effect of structural racism and other social vulnerabilities on Covid-19 mortality in the United States has received some attention, there has been much less discussion (with some notable exceptions) of how structural global inequalities will further exacerbate Covid-related health disparity across the world. This may be partially due to the delayed availability of accurate and comparable data from overwhelmed systems, particularly in low- and middle-income countries. However, early methods to procure and develop treatments and vaccines by some high-income countries reflect ongoing protectionist and nationalistic attitudes that can systemically exclude access for people in regions with weaker health systems. What's needed is a global coordinated effort, based on the principle of solidarity, to foster equitable health care access.

Sexual Functioning in Experienced Meditators.

Given evidence of the benefits of mindfulness for women's sexual difficulties, we investigated the relationship between meditation experience and women's sexual function. Women (N = 450) answered online survey questions about meditation experience, sexual function and desire, interoceptive awareness, health and mood. Women who meditated scored higher than nonmeditators on measures of sexual function and desire, however there was no significant correlation between frequency/length of meditation experience and either of these domains. Global mental health was a significant predictor of both increased sexual function and desire in women who meditate. These findings suggest that, compared to women with no meditation experience, women who meditate to any extent have, on average, improved sexual function associated with better overall mental health.