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Healthy maternal diets can lower the odds of developing pre-eclampsia, a direct and second leading cause of maternal death, globally. However, there is a research gap in low- and middle-income countries (LMIC), which bear a disproportionate burden of these deaths. The objectives of this systematic review were to 1) evaluate the association between dietary patterns in pregnancy and hypertensive disorders, including pre-eclampsia for pregnant and postpartum women in LMIC, and 2) compile barriers and facilitators to an adequate maternal diet. A systematic search was performed on MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health, Web of Science, Cochrane Central Register of Controlled Trials, African Journals Online, the WHO Regional Databases, 2 trial registries, Google Scholar, and reference lists. Included in the analysis were primary research studies of dietary patterns during pregnancy, with pregnancy hypertension outcome(s), and conducted in LMIC. Included studies were assessed using ROBINS-I risk of bias. Thirteen studies were included, of which 5 studies were included in a meta-analysis (Review Manager 5). Lower odds of pre-eclampsia were associated with adequate (compared with no or low) consumption of vegetables (OR 0.38; 95% CI 0.18, 0.80; I2 = 85%; P = 0.01) and adequate (compared with no or low) consumption of fruit (OR 0.42; 95% CI 0.24, 0.71; I2 = 79%; P = 0.008). No firm conclusions could be drawn about the impact on pre-eclampsia odds of any of the following during pregnancy high consumption of meat or grains; a "Western" diet; or alcohol consumption. More LMIC-based research is needed to explore whether the apparent beneficial effects of fruits and vegetables on pre-eclampsia incidence might be enhanced when maternal malnutrition is prevalent, and/or whether other sociodemographic factors might contribute.
Active surveillance of small renal masses highlights the need for accurate prognostication of biopsies.
To comprehensively evaluate the accuracy of biopsies in assessing known prognostic parameters including histologic subtype by comparison with subsequent nephrectomy samples.
We retrospectively identified patients at University of Texas Southwestern Medical Center, Dallas, Texas, who had a biopsy for a renal mass between 2004-2018. Biopsy samples were evaluated for known prognostic factors such as tumor grade, necrosis, sarcomatoid/rhabdoid change, and BRCA1-associated protein-1 (BAP1) status, which we previously showed is an independent prognostic factor for clear cell renal cell carcinoma. Accuracy was determined by comparison with subsequent analyses of nephrectomy specimens. Statistical analyses were performed to assess biopsy accuracy and correlation with tumor size and pathologic stage.
From 805 biopsies with a diagnosis of renal neoplasm, 178 had subsequent resection of the biopsied tumor. Cons. Addition of BAP1 for clear cell renal cell carcinoma may increase prognostic accuracy. If validated, routine incorporation of BAP1 immunohistochemistry in clear cell renal cell carcinoma biopsies may refine prognosis and aid in the selection of patients for active surveillance.Congenital hypothyroidism (CH) is a highly prevalent but treatable neonatal endocrine disorder. Thyroid dyshormonogenesis is the main cause of congenital hypothyroidism in Chinese CH patients, and DUOX2 is the most frequent mutated gene involved in H2O2 production. In humans, the primary sources for H2O2 production are DUOX1 and DUOX2, while in zebrafish there is only a single orthologue for DUOX1 and DUOX2. In this study, duox mutant zebrafish were generated through knockdown duox by morpholino or knockout duox by CRISPR Cas9. The associated phenotypes were investigated and rescued by thyroxine (T4) treatment. Mutant zebrafish displayed hypothyroid phenotypes including growth retardation, goiter and, infertility. Homozygous mutants in adults also displayed extrathyroidal abnormal phenotypes, including lacking barbels, pigmentation defects, erythema in the opercular region, ragged fins, and delayed scales. All these abnormal phenotypes can be rescued by 10 nM T4 treatment. Strikingly, the fertility of zebrafish was dependent on thyroid hormone; T4 treatment should be continued and cannot be stopped over 2 weeks in hypothyroid zebrafish in order to achieve fertility. Thyroid hormones played a role in the developing and maturing of reproductive cells. Our work indicated that duox mutant zebrafish may provide a model for human congenital hypothyroidism.Inborn errors of immunity that present with concomitant immunodeficiency and auto-inflammation are therapeutically challenging; furthermore, complexity is added when they are caused by mutations in genes that encode for proteins expressed beyond immune cells. The ubiquitin-proteasome system is the main intracellular proteolytic machinery and participates in most cellular processes by degrading ubiquitinated proteins. Mutations in proteasome subunits resulting in proteasome deficiency cause a severe auto-inflammatory disease characterized by chronic auto-inflammation neutrophilic dermatosis and fever, collectively referred to as Proteasome Associated Auto-inflammatory Syndromes (PRAAS). POMP is a chaperone for proteasome assembly and AD mutations in POMP cause a form of PRAAS with prominent immunodeficiency referred to as POMP-related auto-inflammation and immune dysregulation (PRAID) manifesting with recurrent, severe and opportunistic infections in addition to inflammatory features that are characteristic for all PRAAS disorders, most importantly early-onset neutrophilic dermatosis. JAK inhibitors partially control the disease in individuals with PRAAS, however life-threatening, recurrent and opportunistic infections in patients with POMP mutations limit immunosuppressive therapies and prompted consideration of hematopoietic stem cell transplant (HSCT). selleckchem We describe successful HSCT in two patients with POMP deficiency. Despite POMP being ubiquitously expressed, the immunologic and auto-inflammatory phenotype were both ameliorated through HSCT which suggests that the clinical and immunological features of PRAID are predominantly derived from a proteasome defect in hematopoietic cells. To our knowledge, these are the first patients with a form of PRAAS cured by HSCT, opening new therapeutic possibilities for these diseases.
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