Aging is the biggest risk factor for cancer, but the mechanisms linking these two processes remain unclear. Using GTEx and TCGA data, we compared genes differentially expressed with age and genes ...differentially expressed in cancer among nine human tissues. In most tissues, aging and cancer gene expression pattern changed in the opposite direction. The exception was thyroid and uterus, where we found transcriptomic changes in the same direction in aging and in their corresponding cancers. The overlapping sets between genes differentially expressed with age and genes differentially expressed in cancer across tissues were enriched for several processes, mainly cell cycle and the immune system. Moreover, cellular senescence signatures, derived from a meta‐analysis, changed in the same direction as aging in human tissues and in the opposite direction of cancer signatures. Therefore, transcriptomic changes in aging and in cellular senescence might relate to a decrease in cell proliferation, while cancer transcriptomic changes shift toward enhanced cell division. Our results highlight the complex relationship between aging and cancer and suggest that, while in general aging processes might be opposite to cancer, the transcriptomic links between human aging and cancer are tissue‐specific.
Tissue‐specific RNA‐seq analysis shows an overall opposite direction of gene expression changes in ageing and cancer, with a few tissues as exceptions. Cellular senescence signatures display similar changes to the ageing transcriptome, but strongly exhibit opposite changes to cancer gene expression patterns.
The açaí seed corresponds to approximately 85% of the fruit's weight and represents ~1.1 million metric tons of residue yearly accumulated in the Amazon region, resulting in an acute environmental ...and urban problem. To extract the highest value from this residue, this study aimed to evaluate its chemical composition to determine the appropriate applications and to develop conversion methods. First, mannan was confirmed as the major component of mature seeds, corresponding to 80% of the seed's total carbohydrates and about 50% of its dry weight. To convert this high mannan content into mannose, a sequential process of dilute-acid and enzymatic hydrolysis was evaluated. Among different dilute-H
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hydrolysis conditions, 3%-acid for 60-min at 121 °C resulted in a 30% mannan hydrolysis yield and 41.7 g/L of mannose. Because ~70% mannan remained in the seed, a mannanase-catalyzed hydrolysis was sequentially performed with 2-20% seed concentration, reaching 146.3 g/L of mannose and a 96.8% yield with 20% solids. As far as we know, this is the highest reported concentration of mannose produced from a residue. Thus, this work provides fundamental data for achieving high concentrations and yields of mannose from açaí seeds, which could add commercial value to the seeds and improve the whole açaí productive chain.
Three drug classes (mineralocorticoid receptor antagonists MRAs, angiotensin receptor–neprilysin inhibitors ARNIs, and sodium/glucose cotransporter 2 SGLT2 inhibitors) reduce mortality in patients ...with heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and β blockers. Each class was previously studied with different background therapies and the expected treatment benefits with their combined use are not known. Here, we used data from three previously reported randomised controlled trials to estimate lifetime gains in event-free survival and overall survival with comprehensive therapy versus conventional therapy in patients with chronic HFrEF.
In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, β blocker, MRA, and SGLT2 inhibitor) versus conventional therapy (ACE inhibitor or ARB and β blocker) in patients with chronic HFrEF by making indirect comparisons of three pivotal trials, EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744). Our primary endpoint was a composite of cardiovascular death or first hospital admission for heart failure; we also assessed these endpoints individually and assessed all-cause mortality. Assuming these relative treatment effects are consistent over time, we then projected incremental long-term gains in event-free survival and overall survival with comprehensive disease-modifying therapy in the control group of the EMPHASIS-HF trial (ACE inhibitor or ARB and β blocker).
The hazard ratio (HR) for the imputed aggregate treatment effects of comprehensive disease-modifying therapy versus conventional therapy on the primary endpoint of cardiovascular death or hospital admission for heart failure was 0·38 (95% CI 0·30–0·47). HRs were also favourable for cardiovascular death alone (HR 0·50 95% CI 0·37–0·67), hospital admission for heart failure alone (0·32 0·24–0·43), and all-cause mortality (0·53 0·40–0·70). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2·7 additional years (for an 80-year-old) to 8·3 additional years (for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1·4 additional years (for an 80-year-old) to 6·3 additional years (for a 55-year-old) of survival compared with conventional therapy.
Among patients with HFrEF, the anticipated aggregate treatment effects of early comprehensive disease-modifying pharmacological therapy are substantial and support the combination use of an ARNI, β blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard.
None.
Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.
This ...study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.
The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval CI: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.
In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction EMPEROR-Reduced; NCT03057977)
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Patients with heart failure with preserved ejection fraction have significant impairment in health-related quality of life. In the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients ...With Chronic Heart Failure With Preserved Ejection Fraction), we evaluated the efficacy of empagliflozin on health-related quality of life in patients with heart failure with preserved ejection fraction and whether the clinical benefit observed with empagliflozin varies according to baseline health status.
Health-related quality of life was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12, 32, and 52 weeks. Patients were divided by baseline KCCQ Clinical Summary Score (CSS) tertiles, and the effect of empagliflozin on outcomes was examined. The effect of empagliflozin on KCCQ-CSS, Total Symptom Score, and Overall Summary Score was evaluated. Responder analyses were performed to compare the odds of improvement and deterioration in KCCQ related to treatment with empagliflozin.
The effect of empagliflozin on reducing the risk of time to cardiovascular death or heart failure hospitalization was consistent across baseline KCCQ-CSS tertiles (hazard ratio, 0.83 95% CI, 0.69-1.00, 0.70 95% CI, 0.55-0.88, and 0.82 95% CI, 0.62-1.08 for scores <62.5, 62.5-83.3, and ≥83.3, respectively;
trend=0.77). Similar results were seen for total heart failure hospitalizations. Patients treated with empagliflozin had significant improvement in KCCQ-CSS versus placebo (+1.03, +1.24, and +1.50 at 12, 32, and 52 weeks, respectively;
<0.01); similar results were seen for Total Symptom Score and Overall Summary Score. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (odds ratio, 1.23 95% CI, 1.10-1.37), ≥10 points (odds ratio, 1.15 95% CI, 1.03-1.27), and ≥15 points (odds ratio, 1.13 95% CI, 1.02-1.26) and lower odds of deterioration ≥5 points in KCCQ-CSS (odds ratio, 0.85 95% CI, 0.75-0.97). A similar pattern was seen at 32 and 52 weeks, and results were consistent for Total Symptom Score and Overall Summary Score.
In patients with heart failure with preserved ejection fraction, empagliflozin reduced the risk for major heart failure outcomes across the range of baseline KCCQ scores. Empagliflozin improved health-related quality of life, an effect that appeared early and was sustained for at least 1 year. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057951.
Abnormalities of Potassium in Heart Failure Ferreira, João Pedro; Butler, Javed; Rossignol, Patrick ...
Journal of the American College of Cardiology,
06/2020, Letnik:
75, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Potassium (K+) is the most abundant cation in humans and is essential for normal cellular function. Alterations in K+ regulation can lead to neuromuscular, gastrointestinal, and cardiac ...abnormalities. Dyskalemia (i.e., hypokalemia and hyperkalemia) in heart failure is common because of heart failure itself, related comorbidities, and medications. Dyskalemia has important prognostic implications. Hypokalemia is associated with excess morbidity and mortality in heart failure. The lower the K+ levels, the higher the risk, starting at K+ levels below approximately 4.0 mmol/l, with a steep risk increment with K+ levels <3.5 mmol/l. Hyperkalemia (>5.5 mmol/l) has also been associated with increased risk of adverse events; however, this association is prone to reverse-causation bias as stopping renin angiotensin aldosterone system inhibitor therapy in the advent of hyperkalemia likely contributes the observed risk. In this state-of-the-art review, practical and easy-to-implement strategies to deal with both hypokalemia and hyperkalemia are provided as well as guidance for the use of potassium-binders.
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•Potassium alterations may have life-threatening consequences.•Hypokalemia is associated with adverse outcomes likely via causal mechanisms.•Hyperkalemia leads to the stopping of renin angiotensin aldosterone system inhibitor that may have adverse consequences.•Correction of both hypokalemia and hyperkalemia offsets their associated risk.
National level Ecological Footprint studies have highlighted disparities among countries. This assessment has proved essential to accurately characterize ecological impacts to specific countries but ...often ignore the heterogeneity within national spaces. Population groups within a country engage in different behaviors and consumption patterns that have a distinct impact on the environment. Understanding the contribution of each group and decomposing their consumption of distinct products is critical to helping environmental organizations and policy makers design more efficient policies and communication strategies that will change critical patterns of human demand. In the current study, national household consumption is split into different population groups corresponding to four particular socio-economic dimensions: main sources of income, age, number of members in the household, and levels of education of the population. The aim is to identify critical groups to provide better ground to generate targeted policies that can achieve better environmental results. Results highlight how diverse ecological impacts can occur among distinct population groups, with the highest per capita Footprint values found in households with higher education level, smaller size and those living from Capital/Property Transfers. These results constitute a new possibility to analyze the impact of policies that tackle specific behaviors of distinct population groups.
Increases in the incidence or severity of hazard events significantly alter the attractiveness of tourism destinations and tourism inflow. In 2018, a significant red tide event limited access to ...marine and coastal areas in Florida, heavily impacting the tourist sector. The purpose of this study was to estimate the economic impacts of red tides in the state economy through the shock in the Airbnb market. We combined microdata on Airbnb properties and water sample records and estimated that water sample indicating the presence of red tide conditions within a county decreases the average daily rate price of Airbnb rentals by $0.45 and the number of reservation days by 345. This event generated $317 million in sales revenue losses and resulted in the loss of nearly 2900 job-years throughout Florida. Knowledge of such consequences is essential to inform decision-making processes for policy makers and tourism management professionals.
The Delphi technique is a qualitative technique which consists of a series of systematic steps to combine the knowledge and opinion of experts regarding a specific topic and reach a consensus as a ...means of scenario building and forecasting. This technique is rarely used in tourism, albeit it has been recommended since 1990 (Green, H., Hunter, C., & Moore, B. 1990. Assessing the environmental impact of tourism development: Use of the Delphi technique. Tourism Management, 11(2), 111-120). The goal of this research note is to demonstrate use of the Delphi technique as a means of building a richer depth of understanding about the likelihood of a Chikungunya outbreak and the impact to the tourism industry.
Abstract The Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions document was ...issued as a guidance for industry and for the Food and Drug Administration. The Expedited Access Pathway was designed as a new program for medical devices that demonstrated the potential to address unmet medical needs for life threatening or irreversibly debilitating conditions. The Food and Drug Administration would consider assessments of a device’s effect on intermediate endpoints that, when improving in a congruent fashion, are reasonably likely to predict clinical benefit. The purpose of this review is to provide evidence to support the use of 3 such intermediate endpoints: natriuretic peptides, such as N-terminal pro–B-type natriuretic peptide/B-type natriuretic peptide, the 6-min walk test distance, and health-related quality of life in heart failure.
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