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Whole grain cereals have been the basis of human diet since ancient times. Due to rich in a variety of unique bioactive ingredients, they play an important role in human health. This review highlights the contents and distribution of primary functional components and their health effects in commonly consumed whole grain cereals, especially dietary fiber, protein, polyphenols, and alkaloids. In general, cereals exert positive effects in the following ways 1) Restoring intestinal flora diversity and increasing intestinal short-chain fatty acids. 2) Regulating plasma glucose and lipid metabolism, thereby the improvement of obesity, cardiovascular and cerebrovascular diseases, diabetes, and other chronic metabolic diseases. 3) Exhibiting antioxidant activity by scavenging free radicals. 4) Preventing gastrointestinal cancer via the regulation of classical signaling pathways. In summary, this review provides a scientific basis for the formulation of whole-grain cereals-related dietary guidelines, and guides people to form scientific dietary habits, so as to promote the development and utilization of whole-grain cereals.Background and Objective Nivolumab and Ipilimumab are immune checkpoint inhibitors. The combination of Nivolumab and Ipilimumab has been reported to have complementary effects in the treatment of metastatic melanoma. The combination therapy of Nivolumab and Ipilimumab (N+I) has shown synergistic effects in cancer immunotherapy but this is still controversial due to the higher incidence of toxicity. Hence, we conducted a meta-analysis to evaluate the efficacy and safety profile of Nivolumab combined with Ipilimumab and compared the different dosing schedules of the N+I combination.Methods By searching in PubMed, PMC, Cochrane library and major conference abstracts, eligible sixteen studies including N+I therapy and Nivolumab monotherapy were selected to analyze overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and high-grade (3-4) adverse effects (AEs). Results Compared with monotherapy of Nivolumab, N+I significantly improved ORR (RR=1.40 [95% CI 1.27, 1.54], P less then 0.00001) and PFS (Hazard Ratio (HR)=0.83 [95% CI 0.77, 0.90], P less then 0.00001), but not OS (HR=0.93 [95% CI 0.84, 1.03], P=0.16). In a sub-analysis, the combination of Nivolumab 1mg/kg plus Ipilimumab 3mg/kg (N1I3) and Nivolumab 3mg/kg plus Ipilimumab 1mg/kg (N3I1) achieved better ORR and PFS than Nivolumab 3mg/kg (N3) alone. Remarkably, OS was also prolonged with the N1I3 combination compared with the N3I1 combination or N3. Furthermore, a higher incidence of high-grade AEs also occurred with the combination therapy of N1I3.Conclusions N+I combination therapy showed greater ORR and PFS compared with Nivolumab monotherapy. N1I3 combination provided the benefit of ORR, PFS and OS but was associated with a higher incidence of toxicity.Background Anger and extreme stress can trigger potentially fatal cardiovascular events in susceptible people. Political elections, such as the 2016 US presidential election, are significant stressors. Whether they can trigger cardiac arrhythmias is unknown. Methods and Results In this retrospective case-crossover study, we linked cardiac device data, electronic health records, and historic voter registration records from 2436 patients with implanted cardiac devices. The incidence of arrhythmias during the election was compared with a control period with Poisson regression. We also tested for effect modification by demographics, comorbidities, political affiliation, and whether an individual's political affiliation was concordant with county-level election results. Overall, 2592 arrhythmic events occurred in 655 patients during the hazard period compared with 1533 events in 472 patients during the control period. There was a significant increase in the incidence of composite outcomes for any arrhythmia (incidence rate ratio [IRR], 1.77 [95% CI, 1.42-2.21]), supraventricular arrhythmia (IRR, 1.82 [95% CI, 1.36-2.43]), and ventricular arrhythmia (IRR, 1.60 [95% CI, 1.22-2.10]) during the election relative to the control period. There was also an increase in specific types of arrhythmia, including atrial fibrillation (IRR, 1.50 [95% CI, 1.06-2.11]), supraventricular tachycardia (IRR, 3.7 [95% CI, 2.2-6.2]), nonsustained ventricular tachycardia (IRR, 1.7 [95% CI, 1.3-2.2]), and daily atrial fibrillation burden (P less then 0.001). Selleckchem EX 527 No significant interaction was found for sex, race/ethnicity, device type, age ≥65 years, hypertension, coronary artery disease, heart failure, political affiliation, or concordance between individual political affiliation and county-level election results. Conclusions There was a significant increase in cardiac arrhythmias during the 2016 US presidential election. These findings suggest that exposure to stressful sociopolitical events may trigger arrhythmogenesis in susceptible people.

Joint distraction triggers intrinsic cartilage repair in animal models of osteoarthritis (OA), corroborating observations in human OA patients treated with joint distraction. The present study explores the still largely elusive mechanism initiating this repair process.

Unilateral OA was induced in the knee joint of 8 dogs using the groove model; the contralateral joint served as a control. After 10 weeks, 4 animals received joint distraction, the other 4 serving as OA controls. Halfway the distraction period (after 4 weeks of a standard 8-week distraction treatment), all animals were euthanized, and joint tissues were collected. A targeted quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was performed of commonly involved processes including matrix catabolism/anabolism, inflammation, and known signaling pathways in OA. In addition, cartilage changes were determined on tissue sections using the canine OARSI (Osteoarthritis Research Society International) histopathology score and collagen type II (COL2A1) immunostaining.

Midway distraction, the distracted OA joint showed an upregulation of proteolytic genes, for example,

,

,

, compared to OA alone and the healthy joints, which correlated with an increased OARSI score. Additionally, genes of the transforming growth factor (TGF)-β and Notch pathway, and markers associated with progenitor cells were increased.

Joint distraction initiates both catabolic and anabolic transcriptional responses. The enhanced turnover, and thereby renewal of the matrix, could be the key to the cartilage repair observed in the months after joint distraction.

Joint distraction initiates both catabolic and anabolic transcriptional responses. The enhanced turnover, and thereby renewal of the matrix, could be the key to the cartilage repair observed in the months after joint distraction.

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