Background Statins may reduce mortality after transcatheter aortic valve replacement (TAVR) through prevention of atherosclerotic events or pleiotropic effects. However, the competing mortality risks ...in TAVR patients may dilute any positive effect of statins. We sought to understand the association of statin use with post-TAVR mortality. Methods and Results We included high- or intermediate-surgical risk patients who underwent TAVR as a part of the PARTNER (Placement of Aortic Transcatheter Valves) II and Sapien 3 trials and registries. Outcomes included 2-year all-cause, cardiovascular, and noncardiovascular mortality. We used propensity score matching to generate matched pairs between those discharged on a statin and those not on a statin after TAVR. Bias was explored with falsification end points (urinary infection, hip fracture). Among 3956 patients who underwent TAVR, we matched 626 patients on a statin with 626 patients not on a statin at discharge. Among matched patients, statin use was associated with lower risk of all-cause (hazard ratio HR 0.65, 95% CI 0.49-0.87, P=0.001), cardiovascular (HR 0.66, 95% CI 0.46-0.96, P=0.030), and noncardiovascular mortality (HR 0.64, 95% CI 0.44-0.99, P=0.045) compared with no statin use. The survival curves diverged within 3 months and continued to separate over a median follow-up of 2.1 years. The falsification end points were similar among groups (urinary infection, P=0.66; hip fracture, P=0.64). Conclusions In an observational, propensity-matched analysis of TAVR patients, statin use was associated with lower rates of cardiovascular and noncardiovascular mortality compared with no statin use. Given the early emergence of the apparent protective effect of statins, this result may be driven either by pleiotropic effects or by residual confounding despite propensity-matching methodology.
Objective
This study aimed to assess the long-term outcome of patients with acromegaly.
Design
This is a multicenter, retrospective, observational study which extends the mean observation period of a ...previously reported cohort of Italian patients with acromegaly to 15 years of follow-up.
Methods
Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included. Life status information was collected either from clinical records or from the municipal registry offices. Standardized mortality ratios (SMRs) were computed comparing data with those of the general Italian population.
Results
A total of 811 patients were included. There were 153 deaths, with 90 expected and an SMR of 1.7 (95% CI 1.4–2.0,
p
< 0.001). Death occurred after a median of 15 (women) or 16 (men) years from the diagnosis, without gender differences. Mortality remained elevated in the patients with control of disease (SMR 1.3, 95% CI 1.1–1.6). In the multivariable analysis, only older age and high IGF1 concentrations at last available follow-up visit were predictors of mortality. The oncological causes of death outweighed the cardiovascular ones, bordering on statistical significance with respect to the general population.
Conclusions
Mortality remains significantly high in patients with acromegaly, irrespectively of disease status, as long as the follow-up is sufficiently long with a low rate of patients lost to follow-up. Therapy strategy including radiotherapy does not have an impact on mortality. Oncological causes of death currently outweigh the cardiovascular causes.
Background Patients with peripheral artery disease (PAD) and coexisting diabetes mellitus (DM) have greater PAD progression and adverse limb events. Our aim was to study whether PAD-specific health ...status differs by DM. Methods and Results The PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) trial is a 16-center international registry that includes patients with recent exacerbations or new-onset symptomatic PAD presenting to specialty clinics. We assessed PAD-specific health status initially and at 3, 6, and 12 months (Peripheral Artery Questionnaire PAQ). We used hierarchical, multivariable, linear regression, and repeated measures analyses to study the association between DM and baseline health status initially and over 3 to 12 months. Models were adjusted for demographics, socioeconomic factors, PAD severity, comorbidities, and psychosocial characteristics. The interaction of DM with PAD revascularization on 3- to 12-month health status was also tested. Of 1204 patients, 398 (33%) had DM (94% type 2). Patients with versus those without DM had lower unadjusted PAQ summary scores at baseline and 3, 6, and 12 months (46.1 versus 50.8, 63.6 versus 68.2, 65.7 versus 71.7, and 65.4 versus 72.6;
≤0.01). In fully adjusted models, the effect of DM on baseline (mean difference, -0.65; 95% CI, -2.86 to 1.56
=0.56) and over 3- to 12-month PAQ summary scores (mean difference, -1.59; 95% CI, -4.06 to 0.88
=0.21) was no longer significant. Twelve-month health status gains following revascularization were similar in both groups (
=0.69). Conclusions Patients with PAD with coexisting DM have poorer health status, mostly explained by the differences in their psychosocial and other comorbidity burden. Patients with PAD and DM versus those without DM experience similar health status benefits following PAD revascularization.
Objective
To determine the influence of serum sodium on physical, psychologic and sexual function.
Methods
This is a cross-sectional survey on 3340 community-dwelling men aged 40–79 years from a ...prospective cohort study in eight European countries, the European Male Ageing Study (EMAS). Participants filled-out the Short Form-36 (SF-36), the Physical Activity Scale for the Elderly (PASE), and the EMAS sexual function questionnaire. For all the analyses, serum sodium corrected for glycaemia (Na
+
G
) was used.
Results
The relationship between Na
+
G
and SF-36 physical function score (F = 3.99; p = 0.01), SF-36 mental health score (F = 7.69; p < 0.001), and PASE score (F = 14.95; p < 0.001) were best described by a quadratic equation, with worse scores for Na
+
G
in either the lowest or the highest ends of the range. After dividing the sample into Na
+
G
< 136 mmol/L (n = 81), 136–147 mmol/L (n = 3223) and > 147 mmol/L (n = 36), linear regression analyses with linear spline functions adjusted for confounders did not confirm these relationships. Similarly, erectile dysfunction and Na
+
G
, were in a quadratic relationship (F = 9.00; p < 0.001). After adjusting for confounders, the linear regression with spline functions denoted a significantly worsened erectile function for increases in serum Na
+
G
> 147 mmol/L (B = 0.15 0.04;0.26, p < 0.01) but no relationship with Na
+
G
< 136 mmol/L. Likewise, the relationship of Na
+
G
with concerns about sexual dysfunction was confirmed only for men with serum Na
+
G
> 147 mmol/L.
Conclusions
This is the first study supporting an association between Na
+
G
and sexual function. A worsening of erection and concerns about sexual function were observed for the highest values of Na
+
G
, independently of other relevant factors.
Salinity is a major constraint on rice productivity worldwide. However, mechanisms of salt tolerance in wild rice relatives are unknown. Root microsomal proteins are extracted from two Oryza ...australiensis accessions contrasting in salt tolerance. Whole roots of 2‐week‐old seedlings are treated with 80 mM NaCl for 30 days to induce salt stress. Proteins are quantified by tandem mass tags (TMT) and triple‐stage Mass Spectrometry. More than 200 differentially expressed proteins between the salt‐treated and control samples in the two accessions (p‐value <0.05) are found. Gene Ontology (GO) analysis shows that proteins categorized as “metabolic process,” “transport,” and “transmembrane transporter” are highly responsive to salt treatment. In particular, mitochondrial ATPases and SNARE proteins are more abundant in roots of the salt‐tolerant accession and responded strongly when roots are exposed to salinity. mRNA quantification validated the elevated protein abundances of a monosaccharide transporter and an antiporter observed in the salt‐tolerant genotype. The importance of the upregulated monosaccharide transporter and a VAMP‐like protein by measuring salinity responses of two yeast knockout mutants for genes homologous to those encoding these proteins in rice are confirmed. Potential new mechanisms of salt tolerance in rice, with implications for breeding of elite cultivars are also discussed.
Summary Background The magnitude of risk of death related to surgery and anaesthesia is not well understood. We aimed to assess whether the risk of perioperative and anaesthetic-related mortality has ...decreased over the past five decades and whether rates of decline have been comparable in developed and developing countries. Methods We did a systematic review to identify all studies published up to February, 2011, in any language, with a sample size of over 3000 that reported perioperative mortality across a mixed surgical population who had undergone general anaesthesia. Using standard forms, two authors independently identified studies for inclusion and extracted information on rates of anaesthetic-related mortality, perioperative mortality, cardiac arrest, American Society of Anesthesiologists (ASA) physical status, geographic location, human development index (HDI), and year. The primary outcome was anaesthetic sole mortality. Secondary outcomes were anaesthetic contributory mortality, total perioperative mortality, and cardiac arrest. Meta-regression was done to ascertain weighted event rates for the outcomes. Findings 87 studies met the inclusion criteria, within which there were more than 21·4 million anaesthetic administrations given to patients undergoing general anaesthesia for surgery. Mortality solely attributable to anaesthesia declined over time, from 357 per million (95% CI 324–394) before the 1970s to 52 per million (42–64) in the 1970s–80s, and 34 per million (29–39) in the 1990s–2000s (p<0·00001). Total perioperative mortality decreased over time, from 10 603 per million (95% CI 10 423–10 784) before the 1970s, to 4533 per million (4405–4664) in the 1970s–80s, and 1176 per million (1148–1205) in the 1990s–2000s (p<0·0001). Meta-regression showed a significant relation between risk of perioperative and anaesthetic-related mortality and HDI (all p<0·00001). Baseline risk status of patients who presented for surgery as shown by the ASA score increased over the decades (p<0·0001). Interpretation Despite increasing patient baseline risk, perioperative mortality has declined significantly over the past 50 years, with the greatest decline in developed countries. Global priority should be given to reducing total perioperative and anaesthetic-related mortality by evidence-based best practice in developing countries. Funding University of Western Ontario.
A ‘citizen science’ approach was evaluated as an approach to organize an extensive radon survey to be representative of the population of either single regions or a whole country. The “RadonTest” ...online system allowed schoolchildren to undertake and record short-term radon tests in their homes. Measurements were carried out in Israel using charcoal in miniature flacons and simple detectors with high sensitivity. Among other things, the “RadonTest” online system implements an alternative principle of building a radon map, allowing the display of radon tests more clearly than the traditional approach, while ensuring the confidentiality of test participants. Examples of public radon maps are presented, and the first test results are discussed. A scientifically based approach for the effective identification of buildings with a high radon concentration, based on the principle of radon regulation, is proposed.
•The “RadonTest” online system is a cloud service, can be used everywhere.•The system builds online database and radon map with automatic geolocation.•Can serve different test methods: charcoal, SSNTD, electrets, continuous monitoring.•User-friendly system: even school children can easily test radon in their homes.•The involvement of school children contributes to the awareness about radon risks.
Abstract
Background
Melaleuca quinquenervia (broad-leaved paperbark) is a coastal wetland tree species that serves as a foundation species in eastern Australia, Indonesia, Papua New Guinea, and New ...Caledonia. While extensively cultivated for its ornamental value, it has also become invasive in regions like Florida, USA. Long-lived trees face diverse pest and pathogen pressures, and plant stress responses rely on immune receptors encoded by the nucleotide-binding leucine-rich repeat (NLR) gene family. However, the comprehensive annotation of NLR encoding genes has been challenging due to their clustering arrangement on chromosomes and highly repetitive domain structure; expansion of the NLR gene family is driven largely by tandem duplication. Additionally, the allelic diversity of the NLR gene family remains largely unexplored in outcrossing tree species, as many genomes are presented in their haploid, collapsed state.
Results
We assembled a chromosome-level pseudo-phased genome for M. quinquenervia and described the allelic diversity of plant NLRs using the novel FindPlantNLRs pipeline. Analysis reveals variation in the number of NLR genes on each haplotype, distinct clustering patterns, and differences in the types and numbers of novel integrated domains.
Conclusions
The high-quality M. quinquenervia genome assembly establishes a new framework for functional and evolutionary studies of this significant tree species. Our findings suggest that maintaining allelic diversity within the NLR gene family is crucial for enabling responses to environmental stress, particularly in long-lived plants.
Resistance genes (R genes) in plants mediate a highly specific response to microbial pathogens, often culminating in localized cell death. Such resistance is generally pathogen race specific and ...believed to be the result of evolutionary selection pressure. Where a host and pathogen do not share an evolutionary history, specific resistance is expected to be absent or rare. Puccinia psidii, the causal agent of myrtle rust, was recently introduced to Australia, a continent rich in myrtaceous taxa. Responses within species to this new pathogen range from full susceptibility to resistance. Using the myrtle rust case study, we examine models to account for the presence of resistance to new encounter pathogens, such as the retention of ancient R genes through prolonged ‘trench warfare’, pairing of resistance gene products and the guarding of host integrity.
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