Bmc Med
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High-grade serous carcinoma (HGSC) is the most frequent and lethal type of ovarian cancer. It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial BRCA1/2 mutations. However, the molecular changes underlying malignant transformation remain unknown. ⋯ These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with BRCA1 germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with BRCA1 germline mutation present with early development and rapid dissemination of HGSC.
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In China, colorectal cancer (CRC) incidence and mortality have been steadily increasing over the last decades. Risk models to predict incident CRC have been developed in various populations, but they have not been systematically externally validated in a Chinese population. This study aimed to assess the performance of risk scores in predicting CRC using the China Kadoorie Biobank (CKB), one of the largest and geographically diverse prospective cohort studies in China. ⋯ Several risk models based on easily obtainable demographic and modifiable lifestyle factor have good discrimination in a Chinese population. The three best performing models have a higher discrimination than using a model based on age alone.
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Multimorbidity poses a major challenge for care coordination. However, data on what non-communicable diseases lead to multimorbidity, and whether the lifetime risk differs between men and women are lacking. We determined sex-specific differences in multimorbidity patterns and estimated sex-specific lifetime risk of multimorbidity in the general population. ⋯ Two thirds of people over 45 will develop multimorbidity in their remaining lifetime, with women at nearly double the risk of multimorbidity involving depression than men. These findings call for programmes of integrated care to consider sex-specific differences to ensure men and women are served equally.
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Onchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission. ⋯ Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions.
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Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function. ⋯ Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption.