A quarter century of granzymes.
Ontology highlight
ABSTRACT:
SUBMITTER: Ewen CL
PROVIDER: S-EPMC3252830 | biostudies-other | 2012 Jan
REPOSITORIES: biostudies-other
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Project description:BackgroundAortic size tends to increase with aging but the extent of this dynamic process has not been evaluated in long-term longitudinal population-based studies. We investigated the incidence of new-onset aortic root (AR) dilatation and its principal correlates among middle-aged adults over a 25-year time period.MethodsA total of 471 participants with measurable echocardiographic parameters at baseline and after a 25-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute AR diameter, AR diameter indexed to body surface area (BSA) and to height were derived from healthy normotensive PAMELA participants.ResultsNew AR dilatation occurred in 7.4% (AR/BSA), 9.1% (AR/height) and 14.6% (absolute AR), respectively. According to the AR/height index, the risk of new dilation was similar in men and women. As for echocardiographic parameters, baseline AR diameter emerged as a key predictor of AR dilation, regardless of the diagnostic criteria and the 10-year change in LVMI was positively associated to new AR/height dilatation. No significant relationship was observed between baseline office and ambulatory systolic/diastolic blood pressure or their changes over time with incident AR dilatation. Baseline and the 25-year change in 24-h pulse pressure were negatively related to new AR dilatation.ConclusionsThe incidence of AR dilatation from mid to late adulthood occurs in a small but clinically relevant fraction of participants and is unaffected by both office and out-office BP. It is significant related to baseline AR diameter and to the 25-year change in LVMI. Our data suggest that echocardiography performed in middle-aged individuals of both sexes may identify those at increased risk of future AR dilatation; moreover, preventing LVH may reduce the risk of progressive AR enlargement.
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Project description:The immersive virtual world platform Second Life (SL) was conceived 25 years ago, when Philip Rosedale founded Linden Lab in 1999 with the intention of developing computing hardware that would allow people to immerse themselves in a virtual world. This initial effort was transformed 4 years later into SL, a universally accessible virtual world centered on the user, with commercial transactions and even its own virtual currency, which fully connects with the concept of the metaverse, recently repopularized after the statements of the chief executive officer of Meta (formerly Facebook) in October 2021. SL is considered the best known virtual environment among higher education professionals. This paper aimed to review medical education in the SL metaverse; its evolution; and its possibilities, limitations, and future perspectives, focusing especially on medical education experiences during undergraduate, residency, and continuing medical education. The concept of the metaverse and virtual worlds was described, making special reference to SL and its conceptual philosophy, historical evolution, and technical aspects and capabilities for higher education. A narrative review of the existing literature was performed, including at the same time a point of view from our teaching team after an uninterrupted practical experience of undergraduate and postgraduate medical education in the last 13 years with >4000 users and >10 publications on the subject. From an educational point of view, SL has the advantages of being available 24/7 and creating in the student the important feeling of "being there" and of copresence. This, together with the reproduction of the 3D world, real-time interaction, and the quality of voice communication, makes the immersive experiences unique, generating engagement and a fluid interrelation of students with each other and with their teachers. Various groups of researchers in medical education have developed experiences during these years, which have shown that courses, seminars, workshops and conferences, problem-based learning experiences, evaluations, teamwork, gamification, medical simulation, and virtual objective structured clinical examinations can be successfully carried out. Acceptance from students and faculty is generally positive, recognizing its usefulness for undergraduate medical education and continuing medical education. In the 25 years since its conception, SL has proven to be a virtual platform that connects with the concept of the metaverse, an interconnected, open, and globally accessible system that all humans can access to socialize or share products for free or using a virtual currency. SL remains active and technologically improved since its creation. It is necessary to continue carrying out educational experiences, outlining the organization, objectives, and content and measuring the actual educational impact to make SL a tool of more universal use.
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Project description:Summary backgroundMultidrug-resistant (MDR) tuberculosis (TB) poses an important challenge in TB management and control. Rifampicin resistance (RR) is a solid surrogate marker of MDR-TB. We investigated the RR-TB clustering rates, bacterial population dynamics to infer transmission dynamics, and the impact of changes to patient management on these dynamics over 27 years in Rwanda.MethodsWe analysed whole genome sequences of a longitudinal collection of nationwide RR-TB isolates. The collection covered three important periods: before programmatic management of MDR-TB (PMDT; 1991-2005), the early PMDT phase (2006-2013), in which rifampicin drug-susceptibility testing (DST) was offered to retreatment patients only, and the consolidated phase (2014-2018), in which all bacteriologically confirmed TB patients had rifampicin DST done mostly via Xpert MTB/RIF assay. We constructed clusters based on a 5 SNP cut-off and resistance conferring SNPs. We used Bayesian modelling for dating and population size estimations, TransPhylo to estimate the number of secondary cases infected by each patient, and multivariable logistic regression to assess predictors of being infected by the dominant clone.ResultsOf 308 baseline RR-TB isolates considered for transmission analysis, the clustering analysis grouped 259 (84.1%) isolates into 13 clusters. Within these clusters, a single dominant clone was discovered containing 213 isolates (82.2% of clustered and 69.1% of all RR-TB), which we named the "Rwanda Rifampicin-Resistant clone" (R3clone). R3clone isolates belonged to Ugandan sub-lineage 4.6.1.2 and its rifampicin and isoniazid resistance were conferred by the Ser450Leu mutation in rpoB and Ser315Thr in katG genes, respectively. All R3clone isolates had Pro481Thr, a putative compensatory mutation in the rpoC gene that likely restored its fitness. The R3clone was estimated to first arise in 1987 and its population size increased exponentially through the 1990s', reaching maximum size (∼84%) in early 2000 s', with a declining trend since 2014. Indeed, the highest proportion of R3clone (129/157; 82·2%, 95%CI: 75·3-87·8%) occurred between 2000 and 13, declining to 64·4% (95%CI: 55·1-73·0%) from 2014 onward. We showed that patients with R3clone detected after an unsuccessful category 2 treatment were more likely to generate secondary cases than patients with R3clone detected after an unsuccessful category 1 treatment regimen.ConclusionsRR-TB in Rwanda is largely transmitted. Xpert MTB/RIF assay as first diagnostic test avoids unnecessary rounds of rifampicin-based TB treatment, thus preventing ongoing transmission of the dominant R3clone. As PMDT was intensified and all TB patients accessed rifampicin-resistance testing, the nationwide R3clone burden declined. To our knowledge, our findings provide the first evidence supporting the impact of universal DST on the transmission of RR-TB.
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