Notes

Western fish-based review unveils large range involving programs for determining environmental position involving lakes.
Single-channel measurements revealed higher RyR2 open probability at low resting Ca
in GRMD cardiomyocytes than in controls. Angiogenesis inhibitor ARM036 prevented those invivo and invitro dysfunctions in GRMD dogs. Myofilament Ca
-sensitivity was increased in permeabilized GRMD cardiomyocytes at short sarcomere length. ARM036 had no effect on this parameter. Cross-bridge cycling kinetics were altered in GRMD myocytes and recovered with ARM036 treatment, which coincided with the level of myosin binding protein-C-S glutathionylation.

GRMD-dogs exhibit early LV dysfunction associated with altered myofilament contractile properties. These abnormalities were prevented pharmacologically by stabilizing RyR2 with ARM036.
GRMD-dogs exhibit early LV dysfunction associated with altered myofilament contractile properties. These abnormalities were prevented pharmacologically by stabilizing RyR2 with ARM036.
Single-center data suggest that the index of microcirculatory resistance (IMR) measured early after heart transplantation predicts subsequent acute rejection.

The goal of this study was to validate whether IMR measured early after transplantation can predict subsequent acute rejection and long-term outcome in a large multicenter cohort.

From 5 international cohorts, 237 patients who underwent IMR measurement early after transplantation were enrolled. The primary outcome was acute allograft rejection (AAR) within 1 year after transplantation. A key secondary outcome was major adverse cardiac events (MACE) (the composite of death, re-transplantation, myocardial infarction, stroke, graft dysfunction, and readmission) at 10 years.

IMR was measured at a median of 7weeks (interquartile range 3-10weeks) post-transplantation. At 1 year, the incidence of AAR was 14.4%. IMR was associated proportionally with the risk of AAR (per increase of 1-U IMR; adjusted hazard ratio [aHR] 1.04; 95% confidence interval [CI] 1.02-1.06; p < 0.001). The incidence of AAR in patients with an IMR≥18 was 23.8%, whereas the incidence of AAR in those with an IMR<18 was 6.3% (aHR 3.93; 95%CI 1.77-8.73; P=0.001). At 10 years, MACE occurred in 86 (36.3%) patients. IMR was significantly associated with the risk of MACE (per increase of 1-U IMR; aHR 1.02; 95%CI 1.01-1.04; P=0.005).

IMR measured early after heart transplantation is associated with subsequent AAR at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized posttransplantation management.
IMR measured early after heart transplantation is associated with subsequent AAR at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized posttransplantation management.
Although mitral valve transcatheter edge-to-edge repair (M-TEER) achieves symptomatic benefit for a broad spectrum of patients with relevant secondary mitral regurgitation, conflicting data exist on its prognostic impact.

Adapted enrollment criteria approaching those used in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients With Functional Mitral Regurgitation) and MITRA-FR (Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation) trials were retrospectively applied to a European real-world registry to evaluate the influence of the respective criteria on outcomes.

A total of 1,022 patients included in the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry and treated with M-TEER (November 2008 to September 2019) were stratified into COAPT-eligible (n=353 [34.5%]) and COAPT-ineligible (n=669 [65.5%]) as well as MITRA-FR-eligible (n=408 [48.3%]) and MITRA-FR-ineligible (n=437 [51.7% specific phenotype demonstrating lower mortality rates. On the contrary, stratification according to adapted MITRA-FR criteria resulted in comparable outcomes.
In this real-world cohort of patients with secondary mitral regurgitation undergoing M-TEER, the retrospective application of adapted COAPT enrollment criteria successfully identified a specific phenotype demonstrating lower mortality rates. On the contrary, stratification according to adapted MITRA-FR criteria resulted in comparable outcomes.
Conventional adherence summary measures do not capture the dynamic nature of adherence.

This study aims to characterize distinct long-term oral anticoagulant adherence trajectories and the factors associated with them in patients with atrial fibrillation.

Adults with incident atrial fibrillation were identified using linked population-based administrative health data in British Columbia, Canada (1996-2019). Group-based trajectory modeling was used to model patients' 90-day proportions of days covered over time to identify distinct 5-year adherence trajectories. Multinomial regression analysis was used to assess the effect of various demographic and clinical factors on exhibiting each adherence trajectory.

The study cohort included 19,749 patients with AF (mean age 70.6 ± 10.6 years), 56% male, mean CHA
DS
-VASc stroke risk score 2.8 ± 1.4. Group-based trajectory modeling identified 4 distinct oral anticoagulants adherence trajectories "consistent adherence" (n=14,631, 74% of the cohort), "rapid declof adherence interventions, and qualitative studies may be needed to better understand the psychosocial determinants and reasons for the behaviors reflected in the identified trajectories.
During positive airway pressure (PAP) therapy for sleep apnea syndromes, the machine detected respiratory event index (REI
) is an important method for clinicians to evaluate the beneficial effects of PAP. There are concerns about the accuracy of this detection, which also confounds a related question-how common and severe are residual events on PAP.

Subjects with OSA who underwent a split night polysomnography were recruited prospectively. Those treated with PAP and tracked by the EncoreAnywhere system were analyzed. The ones who stopped PAP within one month were excluded for this analysis. Compliance, therapy data and waveform data were analyzed. Machine detected versus manually scored events were compared at the 1st, 3rd, 6th and 12th month from PAP initiation. Logistic regression was used to determine factors associated with a high REI
difference.

One hundred and seventy-nine patients with a mean age 59.06 ± 13.97 years old, median body mass index 33.60 (29.75-38.75) kg/m
, and median baseline AHI 46.30 (31.50-65.90) times/hour were included. The difference between the machine detected REI
and manually scored REI
was 10.72 ±8.43 in the first month and remained stable for up to 12 months. Male sex and large leak ≥ 1.5% were more frequent in patients who had an REI
difference of ≥ 5 / hour of use. A titration arousal index ≥ 15/ hour of sleep, and higher ratio of unstable to stable breathing were also associated with an REI
difference ≥ 5 times/hour of use.

There is a substantial and sustained difference between manual and automated event estimates during PAP therapy, and some associated factors were identified.
There is a substantial and sustained difference between manual and automated event estimates during PAP therapy, and some associated factors were identified.We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.IntroductionThe SARS-CoV-2 lineages carrying the amino acid change D614G have become the dominant variants in the global COVID-19 pandemic. By June 2021, all the emerging variants of concern carried the D614G mutation. The rapid spread of the G614 mutant suggests that it may have a transmission advantage over the D614 wildtype.AimOur objective was to estimate the transmission advantage of D614G by integrating phylogenetic and epidemiological analysis.MethodsWe assume that the mutation D614G was the only site of interest which characterised the two cocirculating virus strains by June 2020, but their differential transmissibility might be attributable to a combination of D614G and other mutations. We define the fitness of G614 as the ratio of the basic reproduction number of the strain with G614 to the strain with D614 and applied an epidemiological framework for fitness inference to analyse SARS-CoV-2 surveillance and sequence data.ResultsUsing this framework, we estimated that the G614 mutant is 31% (95% credible interval 28-34) more transmissible than the D614 wildtype. Therefore, interventions that were previously effective in containing or mitigating the D614 wildtype (e.g. in China, Vietnam and Thailand) may be less effective against the G614 mutant.ConclusionOur framework can be readily integrated into current SARS-CoV-2 surveillance to monitor the emergence and fitness of mutant strains such that pandemic surveillance, disease control and development of treatment and vaccines can be adjusted dynamically.BackgroundPopulation-level mathematical models of outbreaks typically assume that disease transmission is not impacted by population density ('frequency-dependent') or that it increases linearly with density ('density-dependent').AimWe sought evidence for the role of population density in SARS-CoV-2 transmission.MethodsUsing COVID-19-associated mortality data from England, we fitted multiple functional forms linking density with transmission. We projected forwards beyond lockdown to ascertain the consequences of different functional forms on infection resurgence.ResultsCOVID-19-associated mortality data from England show evidence of increasing with population density until a saturating level, after adjusting for local age distribution, deprivation, proportion of ethnic minority population and proportion of key workers among the working population. Projections from a mathematical model that accounts for this observation deviate markedly from the current status quo for SARS-CoV-2 models which either assume linearity between density and transmission (30% of models) or no relationship at all (70%). Respectively, these classical model structures over- and underestimate the delay in infection resurgence following the release of lockdown.ConclusionIdentifying saturation points for given populations and including transmission terms that account for this feature will improve model accuracy and utility for the current and future pandemics.Several factors may account for the recent increased spread of the SARS-CoV-2 Delta sub-lineage AY.4.2 in the United Kingdom, Romania, Poland, and Denmark. We evaluated the sensitivity of AY.4.2 to neutralisation by sera from 30 Comirnaty (BNT162b2 mRNA) vaccine recipients in Denmark in November 2021. AY.4.2 neutralisation was comparable to other circulating Delta lineages or sub-lineages. Conversely, the less prevalent B.1.617.2 with E484K showed a significant more than 4-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.
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