Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle

Proteins in the endoplasmic reticulum (ER) require an efficient system of molecular chaperones whose role is to assure their proper folding and to prevent accumulation of unfolded proteins. The response of cells to accumulation of unfolded proteins in the ER is termed "unfolded protein response" (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress, resulting from the accumulation of the unfolded/misfolded proteins. Because intracellular inclusions, containing either amyloid-beta (Abeta) or phosphorylated tau, are the characteristic feature of sporadic inclusion body myositis (s-IBM) muscle biopsies, we studied expression and immunolocalization of five ER chaperones, calnexin, calreticulin, GRP94, BiP/GRP78, and ERp72, in s-IBM and control muscle biopsies. Physical interaction of the ER chaperones with amyloid-beta precursor protein (AbetaPP) was studied by a combined immunoprecipitation/immunoblotting technique in s-IBM and control muscle biopsies, and in AbetaPP-overexpressing cultured human muscle fibers. In all s-IBM muscle biopsies, all five of the ER chaperones were immunodetected in the form of inclusions that co-localized with amyloid-beta. By immunoblotting, expression of ER chaperones was greatly increased as compared to the controls. By immunoprecipitation/immunoblotting experiments, ER chaperones co-immunoprecipitated with AbetaPP. Our studies provide evidence of the UPR in s-IBM muscle and demonstrate for the first time that the ER chaperones calnexin, calreticulin, GRP94, BiP/GRP78, and ERp72 physically associate with AbetaPP in s-IBM muscle, suggesting their playing a role in AbetaPP folding and processing.     

The Gut‒Breast Axis: Programming Health for Life

The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.     

Associations between Family-Based Stress and Dietary Inflammatory Potential among Families with Preschool-Aged Children

Chronic stress is known to influence dietary choices, and stressed families often report poorer diet quality; however, little is known about how family-based stress is linked with dietary patterns that promote inflammation. This study investigated associations between family-based stress and the inflammatory potential of the diet among preschool-aged children and their parents. Parents (n = 212 mothers, n = 146 fathers) and children (n = 130 girls, n = 123 boys; aged 18 months to 5 years) from 241 families participating in the Guelph Family Health Study were included in the analyses. Parents reported levels of parenting distress, depressive symptoms, household chaos, and family functioning. The inflammatory potential of parents’ and children’s diets was quantified using the Dietary Inflammatory Index (DII^®), adjusted for total energy intake (i.e., the E-DII^TM). E-DII scores were regressed onto family stress using generalized estimating equations to account for shared variance among family clusters. Compared to those in homes with low chaos, parents in chaotic homes had significantly more proinflammatory dietary profiles (β = 0.973; 95% CI: 0.321, 1.624, p = 0.003). Similarly, compared to those in well-functioning families, parents in dysfunctional families had significantly more proinflammatory dietary profiles (β = 0.967; 95% CI: 0.173, 1.761, p = 0.02). No significant associations were found between parents’ E-DII scores and parenting distress or depressive symptoms, nor were any associations found for children’s E-DII scores. Results were not found to differ between males and females. Parents in chaotic or dysfunctional family environments may be at increased risk of chronic disease due to proinflammatory dietary profiles. Children’s dietary inflammatory profiles were not directly associated with family stress; however, indirect connections through family food-related behaviours may exist. Future research should prioritize elucidating these mechanisms.     

The Impact of Dental Insurance and Medical Insurance on Dental Care Utilization During Pregnancy

Maternal and Child Health Journal - To measure the association between dental and medical insurance with the receipt of dental cleaning during pregnancy. We analyzed Pregnancy Risk Assessment...     

A socioecological discourse of care or an economistic discourse: which fits better with transition?

Objective : To analyse a ‘socioecological’ health promotion discourse and its relationship to orthodox ‘economistic’ discourse in Australia. Method : In research on health promotion addressing equity and environmental sustainability, we identified a socioecological discourse, based on an ethic of care for people and ecosystems. Using Foucault's concept of discourse as a regime that produces and legitimises certain kinds of knowledge, and ecofeminist historical analysis, we analysed this discourse and its relationship to economism. Results : The socioecological discourse takes social and ecological wellbeing as primary values, while economism takes production and trade of goods and services, measured by money, as primary. Following British invasion, property‐owning white men in Australia had the right to control and profit from land, trade, and the work of women and subordinate peoples. A knowledge regime using money as a primary measure reflects this history. In contrast, a First Nations’ primary value expressed in the study was ‘look after the land and the children’. Conclusion and implications for public health : Public health often attempts to express value through economism, using monetary measures. However, socioecological discourse, expressed for example through direct measures of social and ecological wellbeing, appears more fit for purpose in promoting a fair and sustainable society.     

Eribulin combined with radiation therapy in a young patient re-irradiated for a new lesion of breast cancer

Eribulin is widely used in the treatment of metastatic breast cancer, with a manageable toxicity profile. This aggressive disease often requires systemic and local treatments, comprising surgery or radiotherapy. However, eribulin is usually discontinued during radiation therapy due to the lack of data concerning the safety of this combination, especially in the setting of repeat locoregional radiation therapy. Our patient was diagnosed with ER positive invasive ductal carcinoma of the left breast initially treated by surgery, radiation therapy, chemotherapy, and hormone therapy. She then received various lines of chemotherapy for multiple triple-negative relapses in the left axillary region. Since October 2020, she has been treated by eribulin. In order to improve local control, it was decided to add local radiation therapy to the region of recurrence in addition to systemic therapy. She underwent radiation therapy concomitantly with eribulin from February to March 2021. Treatment was very well tolerated, and no acute toxicity was reported. This is the first published case of repeat locoregional radiation therapy in combination with eribulin.     

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66–0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66–0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = −0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.     

Sex-Positivity,Medical Mistrust,and PrEP Conspiracy Beliefs Among HIV-Negative Cisgender Black Sexual Minority Men in Atlanta,Georgia

Because the public health response to the disproportionate HIV burden faced by Black sexual minority men (BSMMM) has focused on sexual risk reduction and disease prevention, other vital components of sexual health (e.g., intimacy, pleasure, benefits of sex) have been often overlooked. Sex-positive describes a more open, holistic approach toward sex and sexuality that prioritizes these other components, though such an approach is rarely applied to BSMM's sexual health. For sex-positive BSMM, risk/preventive discourse may foster or exacerbate medical mistrust as a reaction to the dissonance between how these men view sexual health and how the medical establishment views it, which may discourage sexual healthcare-seeking. We assessed sex-positivity and its association with medical mistrust and PrEP conspiracy beliefs among 206 HIV-negative cisgender BSMM in Atlanta, Georgia. We performed exploratory factor analytic procedures on responses to a sex-positivity scale, followed by multivariable linear regressions to determine sex-positivity’s associations with medical mistrust and PrEP conspiracy beliefs. We extracted two sex-positivity factors: sexual freedom (α?=?0.90), reflecting openness toward casual sex and rejection of sexual mores, and essence of sex (α?=?0.77), reflecting the intimate, relational, and pleasurable qualities of sex. Sexual freedom was independently associated with perceived provider deception (β?=?0.19, CI?=?0.04, 0.34). Essence of sex was independently associated with PrEP conspiracy beliefs (β?=?0.16, CI?=?0.02, 0.31) and marginally associated with perceived provider deception (β?=?0.14, CI?=???0.00, 0.29). Healthcare providers and public health practitioners may cultivate greater trust with BSMM by incorporating a sex-positive approach into patient/participant interactions, clinical decision-making, and interventions. Improving access to sexual pleasure acknowledges BSMM’s right to optimal, holistic sexual health.