Prognostic value of adiponectin for cardiovascular disease and mortality.

Context: Low adiponectin concentrations are associated with the presence of an adverse cardiovascular disease (CVD) risk profile. Objective: We studied the predictive value of adiponectin levels for all-cause and CVD mortality and CVD morbidity. Design, Setting, and Participants: This was a population-based cohort study in Hoorn, The Netherlands, which started in 1989 and included 2484 participants, aged 50-75 yr. Main Outcome Measures: Hazard ratios (HRs) with 95% confidence interval per SD change in log-adiponectin for all-cause and CVD mortality and CVD morbidity were calculated. Results: Adiponectin was determined for 1077 men and 1248 women. Higher adiponectin reduced the risk of nonfatal CVD in women [HR with 95% confidence interval 0.72 (0.61-0.90) in women and 0.92 (0.79-1.06) in men], but not the risk of all-cause or CVD mortality. In contrast, after adjustment for cardiovascular risk factors, higher adiponectin was a significant predictor of all-cause and CVD mortality [HR for CVD mortality 1.45 (1.10-1.92) in women and 1.30 (1.04-1.63) in men]. Higher adiponectin was associated with an increased risk of CVD mortality in people with prevalent CVD [HR 1.27 (0.98-1.63)] and with reduced risk in people without [HR 0.90 (0.73-1.11)]. After adjustment for cardiovascular risk factors, the HRs for CVD mortality were 1.60 (1.14-2.23) for patients with and 1.38 (1.06-1.80) for patients without prevalent CVD. Conclusions: High levels of adiponectin predict mortality, in particular in patients with prevalent CVD. We hypothesize that adiponectin protects against metabolic and vascular diseases, but in patients already afflicted with CVD, adiponectin is compensatory up-regulated and, therefore, indicates a high mortality risk

Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and woman. The Hoorn Study.

OBJECTIVE: Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS: The Hoorn Study is a cohort study among Caucasians, aged 50-75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS: Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23-1.18) in men and 0.15 (0.06-0.39) in women for type 2 diabetes and 0.90 (0.51-1.61) and 0.28 (0.16-0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32-1.91] and 0.62 [0.21-1.81]) and with IGM (1.20 [0.61-2.35] and 0.48 [0.26-0.90]), respectively. CONCLUSIONS: A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes

GPU-accelerated bi-objective treatment planning for prostate high-dose-rate brachytherapy

Purpose: The purpose of this study is to improve upon a recently introduced bi-objective treatment planning method for prostate high-dose-rate (HDR) brachytherapy (BT), both in terms of resulting

A prediction rule for shoulder pain related sick leave: a prospective cohort study.

Shoulder pain is common in primary care, and has an unfavourable outcome in many patients. Information about predictors of shoulder pain related sick leave in workers is scarce and inconsistent. The objective was to develop a clinical prediction rule for calculating the risk of shoulder pain related sick leave for individual workers, during the 6 months following first consultation in general practice

Attitudes and perceptions towards the use of artificial intelligence chatbots in medical journal peer review: A protocol for a large-scale, international cross-sectional survey

Background: Artificial intelligence (AI) chatbots are advanced conversational programmes capable of performing tasks such as identifying methodological flaws, verifying references, and improving language clarity in manuscripts. Their use in peer review has the potential to enhance efficiency, reduce reviewer workload, and address inconsistencies in review quality. However, concerns remain regarding their reliability, ethical implications, and transparency in decision-making, and little is known about how peer reviewers perceive these tools.Objectives: To assess peer reviewers’ attitudes and perceptions towards the use of AI chatbots in the peer review process, including their familiarity with AI, perceived benefits and challenges, ethical considerations, and expectations for future roles.Methods: An international cross-sectional survey will be conducted among academic peer reviewers. The survey will collect data on participants’ prior experience with AI, perceptions of the utility of chatbots in supporting peer review, concerns related to ethics and transparency, and anticipated future applications.Results: This study will report descriptive and comparative analyses of reviewers’ responses, highlighting patterns in attitudes and perceptions by demographic and professional characteristics.Conclusions: The findings may offer evidence to inform the development of future policies and best practices for the ethical and effective integration of AI chatbots in peer review, with the goal of improving review quality while addressing potential risks

Dysferlin Forms a Dimer Mediated by the C2 Domains and the Transmembrane Domain In Vitro and in Living Cells

Dysferlin was previously identified as a key player in muscle membrane repair and its deficiency leads to the development of muscular dystrophy and cardiomyopathy. However, little is known about the oligomerization of this protein in the plasma membrane. Here we report for the first time that dysferlin forms a dimer in vitro and in living adult skeletal muscle fibers isolated from mice. Endogenous dysferlin from rabbit skeletal muscle exists primarily as a ∼460 kDa species in detergent-solubilized muscle homogenate, as shown by sucrose gradient fractionation, gel filtration and cross-linking assays. Fluorescent protein (YFP) labeled human dysferlin forms a dimer in vitro, as demonstrated by fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) analyses. Dysferlin also dimerizes in living cells, as probed by fluorescence resonance energy transfer (FRET). Domain mapping FRET experiments showed that dysferlin dimerization is mediated by its transmembrane domain and by multiple C2 domains. However, C2A did not significantly contribute to dimerization; notably, this is the only C2 domain in dysferlin known to engage in a Ca-dependent interaction with cell membranes. Taken together, the data suggest that Ca-insensitive C2 domains mediate high affinity self-association of dysferlin in a parallel homodimer, leaving the Ca-sensitive C2A domain free to interact with membranes

Protocol of the COSMIN study: COnsensus-based Standards for the selection of health Measurement INstruments

BACKGROUND: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist. METHOD: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist. DISCUSSION: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase

High-speed AFM height spectroscopy reveals µs-dynamics of unlabeled biomolecules

Dynamics are fundamental to the functions of biomolecules and can occur on a wide range of time and length scales. Here we develop and apply high-speed AFM height spectroscopy (HS-AFM-HS), a technique whereby we monitor the sensing of a HS-AFM tip at a fixed position to directly detect the motions of unlabeled molecules underneath. This gives Angstrom spatial and microsecond temporal resolutions. In conjunction with HS-AFM imaging modes to precisely locate areas of interest, HS-AFM-HS measures simultaneously surface concentrations, diffusion coefficients and oligomer sizes of annexin-V on model membranes to decipher key kinetics allowing us to describe the entire annexin-V membrane-association and self-assembly process in great detail and quantitatively. This work displays how HS-AFM-HS can assess the dynamics of unlabeled bio-molecules over several orders of magnitude and separate the various dynamic components spatiotemporally