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Risk for atherosclerotic cardiovascular disease (ASCVD) shows considerable heterogeneity both in generally healthy persons and in those with known ASCVD. The foundation of preventive cardiology begins with assessing baseline ASCVD risk using global risk scores based on standard office-based measures. Persons at low risk are generally recommended for lifestyle management only and those at highest risk are recommended for both lifestyle and pharmacologic therapy. Additional "risk enhancing" factors, including both traditional risk factors and novel biomarkers and inflammatory factors can be used to further assess ASCVD risk, especially in those at borderline or intermediate risk. There are also female-specific risk enhancers, social determinants of health, and considerations for high-risk ethnic groups. learn more Screening for subclinical atherosclerosis, especially with the use of coronary calcium screening, can further inform the treatment decision if uncertain based on the above strategies. Persons with pre-existing ASCVD also have variable risk, affected by the number of major ASCVD events, whether recurrent events have occurred recently, and the presence of other major risk factors or high-risk conditions. Current guidelines define high to very high risk ASCVD accordingly. Accurate ASCVD risk assessment is crucial for the appropriate targeting of preventive therapies to reduce ASCVD risk. Finally, the clinician-patient risk discussion focusing on lifestyle management and the risks and benefits of evidence-based pharmacologic therapies to best lower ASCVD risk is central to this process. This clinical practice statement provides the preventive cardiology specialist with guidance and tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events.Muscle stem cells (MuSCs) experience age-associated declines in number and function, accompanied by mitochondrial electron transport chain (ETC) dysfunction and increased reactive oxygen species (ROS). The source of these changes, and how MuSCs respond to mitochondrial dysfunction, is unknown. We report here that in response to mitochondrial ROS, murine MuSCs directly fuse with neighboring myofibers; this phenomenon removes ETC-dysfunctional MuSCs from the stem cell compartment. MuSC-myofiber fusion is dependent on the induction of Scinderin, which promotes formation of actin-dependent protrusions required for membrane fusion. During aging, we find that the declining MuSC population accumulates mutations in the mitochondrial genome, but selects against dysfunctional variants. In the absence of clearance by Scinderin, the decline in MuSC numbers during aging is repressed; however, ETC-dysfunctional MuSCs are retained and can regenerate dysfunctional myofibers. We propose a model in which ETC-dysfunctional MuSCs are removed from the stem cell compartment by fusing with differentiated tissue.This introduction to the Special Issue in Affective Science on structural racism lays a challenge to affective science researchers improve the inefficiency in our science. It describes how structural racism leads to inefficiencies in idea generation, technological development, training, and career progression in our science, limiting its ability to fully discover the role of affect in the human condition. It briefly describes the content of the special issue, and attempts to start a dialogue about best practices for inclusive science.
Patients with CKD often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may affect the metabolism or efficacy of antihypertensive agents. We report changes in hypertension control after providing a panel of 11 pharmacogenomic predictors of antihypertensive response.
A prospective cohort with CKD and hypertension was followed to assess feasibility of pharmacogenomic testing implementation, self-reported provider utilization, and BP control. The analysis population included 382 subjects with hypertension who were genotyped for cross-sectional assessment of DGIs, and 335 subjects followed for 1 year to assess systolic BP (SBP) and diastolic BP (DBP).
Most participants (58%) with uncontrolled hypertension had a DGI reducing the efficacy of one or more antihypertensive agents. Subjects with a DGI had 1.85-fold (95% CI, 1.2- to 2.8-fold) higher odds of uncontrolled hypertension, as compared with those without a DGI, adjusted for race, health system (safety-net hospital versus other locations), and advanced CKD (eGFR <30 ml/min).
-reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (odds ratio [OR], 5.2; 95% CI, 1.9 to 14.7).
-intermediate or -poor metabolizers had less frequent uncontrolled hypertension compared with normal metabolizers taking metoprolol or carvedilol (OR, 0.55; 95% CI, 0.3 to 0.95). In 335 subjects completing 1-year follow-up, SBP (-4.0 mm Hg; 95% CI, 1.6 to 6.5 mm Hg) and DBP (-3.3 mm Hg; 95% CI, 2.0 to 4.6 mm Hg) were improved. No significant difference in SBP or DBP change were found between individuals with and without a DGI.
There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.
There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.
The root of many kidney diseases in humans can be traced to alterations or damage to subcellular organelles. Mitochondrial fragmentation, endoplasmic reticulum (ER) stress, and lysosomal inhibition, among others, ultimately contribute to kidney injury and are the target of therapeutics in development. Although recent technological advancements allow for the understanding of disease states at the cellular level, investigating changes in subcellular organelles from kidney tissue remains challenging.
Using structured illumination microscopy, we imaged mitochondria and other organelles from paraffin sections of mouse tissue and human kidney biopsy specimens. The resulting images were 3D rendered to quantify mitochondrial size, content, and morphology. Results were compared with those from transmission electron microscopy and segmentation.
Super-resolution imaging reveals kidney tubular epithelial cell mitochondria in rodent and human kidney tissue form large, interconnected networks under basal conditions, ochondria in kidney tissue. Maintaining mitochondrial interconnectivity and morphology protects against kidney injury. Super-resolution imaging has the potential to both drive discovery of novel pathobiologic mechanisms in kidney tissue and broaden the diagnoses that can be made on human biopsy specimens.
The Recovery Approach is about supporting people to live the best life they possibly can. This paper reports on a 2008-11 study of a recovery-focussed, one-to-one coaching programme called Whole Life (WL) in a group of people with stabilised schizophrenia. WL comprises 15 modules, each addressing an aspect of life that may pose challenges for someone with mental illness. It involves regular meetings with a coach, additional homework activities and lasts approximately one-year. This level of commitment requires participants to be motivated and enthusiastic.
This was a non-randomised feasibility study, designed to assess acceptability and potential benefits of WL. The WL group was compared to another group of people with the same diagnosis, who received their usual treatment. This was not a strict control group. The primary outcome measure was the Social Adaptation Self-Assessment Scale.
Of those recruited to the WL group, 33/44 (75%) completed the full programme. WL participants showed an 11-point increaious and chronic mental illness, although we do not know how it compares to other interventions. We discuss some methodological limitations of the study.
Pancreatic cancer (PC) is one of the most aggressive tumours, and better risk stratification among patients is required to provide tailored treatment. The meaning of radiomics and texture analysis as predictive techniques are not already systematically assessed. The aim of this study is to assess the role of radiomics in PC.
A PubMed/MEDLINE and Embase systematic review was conducted to assess the role of radiomics in PC. The search strategy was 'radiomics [All Fields] AND ("pancreas" [MeSH Terms] OR "pancreas" [All Fields] OR "pancreatic" [All Fields])' and only original articles referred to PC in humans in the English language were considered.
A total of 123 studies and 183 studies were obtained using the mentioned search strategy on PubMed and Embase, respectively. After the complete selection process, a total of 56 papers were considered eligible for the analysis of the results. Radiomics methods were applied in PC for assessment technical feasibility and reproducibility aspects analysis, risk stratification, biologic or genomic status prediction and treatment response prediction.
Radiomics seems to be a promising approach to evaluate PC from diagnosis to treatment response prediction. Further and larger studies are required to confirm the role and allowed to include radiomics parameter in a comprehensive decision support system.
Radiomics seems to be a promising approach to evaluate PC from diagnosis to treatment response prediction. Further and larger studies are required to confirm the role and allowed to include radiomics parameter in a comprehensive decision support system.In this study, dynamic variations in physicochemical characteristics of polysaccharides from 'Wuyi rock' tea (WYP) at different simulated digestion and fecal fermentation stages in vitro were studied. Results revealed that physicochemical characteristics of WYP were slightly altered after the simulated digestion in vitro, and its digestibility was about 8.38%. Conversely, physicochemical characteristics of the indigestible WYP, including reducing sugar, chemical composition, constituent monosaccharide, molecular weight, and FT-IR spectrum, were obviously altered after the fecal fermentation in vitro, and its fermentability was about 42.18%. Notably, the indigestible WYP could remarkably modulate the microbial composition via promoting the proliferation of profitable intestinal microbes, such as Bacteroides, Lactococcus, and Bifidobacterium. Moreover, it could also enhance the generation of short-chain fatty acids. The results showed that WYP was slightly digested in the gastrointestinal tract in vitro, but could be obviously utilized by intestinal microbiota, and might possess the potential to improve intestinal health.This study aimed to identify compounds in 12 minor Zingiberaceae spices grown in Indonesia linked with in vitro α-glucosidase inhibitor and antioxidant (DPPH, FRAP, CUPRAC) activities using SPME-GC/MS volatilomics. The results illustrated that Zingiber aromaticum Val., Alpinia malaccensis (Burm.f.) Roscoe, Amomum compactum Sol. ex Maton, and Zingiber purpureum Roscoe had the highest α-glucosidase inhibitor and DPPH, FRAP, CUPRAC antioxidant activities, respectively. Also, the total phenolic content positively influenced DPPH, FRAP, and CUPRAC antioxidant activities. The strongest positive correlation with α-glucosidase inhibitor and DPPH antioxidant activities was found in eucalyptol; whereas o-cymene and terpinen-4-ol had the strongest correlations with FRAP and CUPRAC antioxidants, respectively. Furthermore, the molecular docking analysis revealed that all compounds with a strong correlation with α-glucosidase inhibitor activity (based on their OPLS VIP score) had binding energies (-5.06 - -6.26 kcal/mol) close to Acarbose (-10.
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