Bmc Med
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Endometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune lesion clearance, a pro-inflammatory endometrial environment, and systemic inflammation. Comprehensive understanding of endometriosis immune pathophysiology in different hormonal milieu and disease severity has been hampered by limited direct characterization of immune populations in endometrium, blood, and lesions. Simultaneous deep phenotyping at single-cell resolution of complex tissues has transformed our understanding of the immune system and its role in many diseases. Herein, we report mass cytometry and high dimensional analyses to study immune cell phenotypes, abundance, activation states, and functions in endometrium and blood of women with and without endometriosis in different cycle phases and disease stages. ⋯ A greater inflammatory phenotype and decreased phagocytic capacity of endometrial macrophages in endometriosis are consistent with defective clearance of endometrial cells shed during menses and in tissue homeostasis, with implications in endometriosis pathogenesis and pathophysiology. Different proportions of monocytes and plasmacytoid dendritic cells in blood from endometriosis suggest systemically aberrant functionality of the myeloid system opening new venues for the study of biomarkers and therapies for endometriosis.
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Ketone body β-hydroxybutyrate (BHB) has received more and more attentions, because it possesses a lot of beneficial, life-preserving effects in the fields of clinical science and medicine. However, the role of BHB in intestinal inflammation has not yet been investigated. ⋯ In summary, we show that BHB promotes M2 macrophage polarization through the STAT6-dependent signaling pathway, which contributes to the resolution of intestinal inflammation and the repair of damaged intestinal tissues. Our finding suggests that exogenous BHB supplement may be a useful therapeutic approach for IBD treatment.
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Obesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify "high-risk" offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system. ⋯ We devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in "high-risk" infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care.
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People who use illicit opioids are more likely to be admitted to hospital than people of the same age in the general population. Many admissions end in discharge against medical advice, which is associated with readmission and all-cause mortality. Opioid withdrawal contributes to premature discharge. We sought to understand the barriers to timely provision of opioid substitution therapy (OST), which helps to prevent opioid withdrawal, in acute hospitals in England. ⋯ Many hospitals in England have policies that likely prevent timely and effective OST. This was underpinned by the 'low-risk' categorisation of OST delay in the ODMT. Delays to continuity of OST between community and hospital settings may contribute to inpatient opioid withdrawal and increase the risk of discharge against medical advice. Acute hospitals in England require standardised best practice policies that account for the needs of this patient group.
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Reliable assessment of glycemia is central to the management of diabetes. The kidneys play a vital role in maintaining glucose homeostasis through glucose filtration, reabsorption, consumption, and generation. This review article highlights the role of the kidneys in glucose metabolism and discusses the benefits, pitfalls, and evidence behind the glycemic markers in patients with chronic kidney disease. We specifically highlight the role of continuous glucose monitoring as an emerging minimally invasive technique for glycemic assessment.