Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.
ImportanceLonger leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.ObjectiveTo evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypesDesign, Setting, and ParticipantsThis is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.ExposureLTL.Main Outcomes and MeasuresCardiovascular imaging traits and HF.ResultsOf 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10−6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.Conclusions and RelevanceIn this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.
ObjectivePatient understanding of angiography and angioplasty is often incomplete at the time of consent. Language barriers and time constraints are significant obstacles, particularly in the urgent setting. We introduced digital animations to support consent and assessed the effect on patient understanding.MethodsMulti-language animations explaining angiography and angioplasty (www.explainmyprocedure.com/heart) were introduced at nine district hospitals for patients with acute coronary syndrome before urgent transfer to a cardiac centre for their procedure. Reported understanding of the reason for transfer, the procedure, its benefits and risks in 100 consecutive patients were recorded before introduction of the animations into practice (no animation group) and in 100 consecutive patients after their introduction (animation group). Patient understanding in the two groups was compared.ResultsFollowing introduction, 83/100 patients reported they had watched the animation before inter-hospital transfer (3 declined and 14 were overlooked). The proportions of patients who understood the reason for transfer, the procedure, its benefits and risks in the no animation group were 58%, 38%, 25% and 7% and in the animation group, 85%, 81%, 73% and 61%, respectively. The relative improvement (ratio of proportions) was 1.5 (95% CI 1.2 to 1.8), 2.1 (1.6 to 2.8), 2.9 (2.0 to 4.2) and 8.7 (4.2 to 18.1), respectively (p<0.001 for all comparisons).ConclusionUse of animations explaining angiography and angioplasty is feasible before urgent inter-hospital transfer and was associated with substantial improvement in reported understanding of the procedure, its risks and its benefits. The approach is not limited to cardiology and has the potential to be applied to all specialties in medicine.
from the original CHARIOT study and both the electronic clinical record and coding data were interrogated to ascertain the clinical outcome. Results 491 (8.6%) patients had hs-cTnI concentrations above the manufacturer's ULN. There were 4157 (72.8%) patients in whom the hs-cTnI was performed solely as part of the study, with 309 (7.4%) of these above the ULN. Five patients died in ED. Of the remaining patients, 3603 (63.2%) were admitted to hospital. The rate of admission increased with rising hs-cTnI concentrations (table 1). A cardiovascular diagnosis was the most frequent discharge diagnosis in those with a hs-cTnI above the ULN. However, a neurological condition was most common in the patients in whom the test was only performed as part of the study. Increasing hs-cTnI concentrations were associated with increasing in hospital mortality regardless of whether the hs-cTnI was requested for clinical reasons or not (figures 1 & 2). Furthermore, hs-cTnI demonstrated good discriminative ability for in-patient mortality (area under receiver operator curve 0.834). Hs-cTnI above the ULN remained an independent predictor of mortality on multivariate analysis. The median length of stay was also associated with increasing hs-cTnI concentrations. Conclusion In consecutive patients presenting to ED, hs-cTnI elevation is common. Furthermore, increasing hs-cTnI concentrations are associated with increased admission rates from ED, longer in-patient stays and higher in-hospital mortality. Hs-cTnI may therefore represent a biomarker for in hospital outcomes in these patients. Conflict of Interest Unrestricted research grant from Beckman Coulter (who had no role in the design, analysis, interpretation of the study)
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