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BACKGROUND Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. METHODS In a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (twcting AHTs (OR = 0.672 (CI 0.548-0.825, p less then 0.001)). CONCLUSION Among older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.Inhibition of the key glycolytic activator 6-phosphofructokinase 2/fructose-2,6-bisphosphatase-3 (PFKFB3) by 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) strongly attenuates pathological angiogenesis in cancer and inflammation. In addition to modulating endothelial proliferation and migration, 3PO also dampens proinflammatory activation of endothelial cells and experimental inflammation in vivo, suggesting a potential for 3PO in the treatment of chronic inflammation. The aim of our study was to explore if the anti-inflammatory action of 3PO in human endothelial cells was mediated by inhibition of PFKFB3 and glycolysis and assess if other means of PFKFB3 inhibition reduced inflammatory activation in a similar manner. We found that 3PO caused a rapid and transient reduction in IL-1β- and TNF-induced phosphorylation of both IKKα/β and JNK, thus inhibiting signaling through the NFκB and the stress-activated kinase pathways. However, in contrast to 3PO-treatment, neither shRNA-mediated silencing of PFKFB3 nor treatment with the alternative PFKFB3 inhibitor 7,8-dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (YN1) prevented cytokine-induced NFκB signaling and upregulation of the adhesion molecules VCAM-1 and E-selectin, implying off target effects of 3PO. Collectively, our results suggest that the anti-inflammatory action of 3PO in human endothelial cells is not limited to inhibition of PFKFB3 and cellular glycolysis.BACKGROUND We investigated changes in clinical characteristics of SGLT2i and GLP-1RA real-world initiators in Denmark before/after landmark cardiovascular outcome trials. METHODS We compared first-time SGLT2i (25,070) and GLP-1RA (14,671) initiators to initiators of DPP-4i (n = 34,079), a class without proven cardiovascular benefits. We used linked population-based healthcare data to examine initiation incidence, medication patterns, and pre-existing atherosclerotic cardiovascular disease (ASCVD) during 2014-2017. RESULTS Nationwide incidence of SGLT2i initiators increased 3.6-fold (53/100,000 to 172/100,000 per year) vs. a 1.5-fold increase for GLP-1RA. DPP-4i initiation remained stable. From the end of 2015, SGLT2i was increasingly used as 2nd-line therapy, while medication patterns were much more stable for GLP-1RA. Among SGLT2i users, ASCVD increased slightly from 28% to 30%; age- and gender-adj. prevalence ratio (aPR) = 1.03 (95% CI0.97-1.10). In contrast, among GLP-1RA initiators, baseline ASCVD declined from 29% to 27% (aPR 0.90 (95% CI0.84-0.97)), and in DPP-4i initiators from 31% to 29% (aPR 0.91 (95% CI0.88-0.96)). CONCLUSIONS Following the EMPA-REG OUTCOME trial in 2015, SGLT2i have become increasingly used as 2nd-line treatment in everyday clinical practice, with only minor increases in patient proportions with ASCVD. For GLP-1RA, we observed more stable therapy lines and slightly decreasing ASCVD in new users despite the LEADER trial.BACKGROUND AND AIM Coronary heart disease (CHD) is a chronic complex disease caused by a combination of factors such as lifestyle behaviors and environmental and genetic factors. We conducted this study to evaluate the risk factors affecting the development of CHD in Xinjiang, and to obtain valuable information for formulating appropriate local public health policies. METHOD We conducted a nested case-control study with 277 confirmed CHD cases and 554 matched controls. The association of the risk factors with the risk of CHD was assessed using the multivariate Cox proportional hazard model. Multiplicative interactions were evaluated by entering interaction terms in the Cox proportional hazard model. The additive interactions among the risk factors were assessed by the index of additive interaction. https://www.selleckchem.com/products/gpna.html RESULTS The risk of CHD increased with frequent high-fat food consumption, dyslipidemia, obesity, and family history of CHD after adjustment for drinking, smoking status, hypertension, diabetes, family history of hypertension, and family history of diabetes. We noted consistent interactions between family history of CHD and frequent high-fat food consumption, family history of CHD and obesity, frequent high-fat food consumption and obesity, frequent high-fat food consumption and dyslipidemia, and obesity and dyslipidemia. The risk of CHD events increased with the presence of the aforementioned interactions. CONCLUSIONS Frequent high-fat food consumption, family history of CHD, dyslipidemia and obesity were independent risk factors for CHD, and their interactions are important for public health interventions in patients with CHD in Xinjiang.The role that women play in fisheries around the world is receiving increasing international attention yet the contributions by women to fisheries catches continues to be overlooked by society, industry and policy makers. Here, we address this lack of visibility with a global estimation of small-scale fisheries catches by women. Our estimates reveal that women participate in small-scale fishing activities in all regions of the world, with approximately 2.1 million (± 86,000) women accounting for roughly 11% (± 4%) of participants in small-scale fishing activities, i.e., catching roughly 2.9 million (± 835,000) tonnes per year of marine fish and invertebrates. The landed value of the catch by women is estimated at USD 5.6 billion (± 1.5 billion), with an economic impact of USD 14.8 billion per year (± 4 billion), which is equivalent to 25.6 billion real 2010 dollars (± 7.2 billion). These catches are mostly taken along the shoreline, on foot, or from small, non-motorized vessels using low-technology, low-emission gears in coastal waters.
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