Mccallumebbesen0351
Immune checkpoint inhibitors (ICIs) are an emerging option for several advanced metastatic cancers, but may have cardiotoxic effects. The prognostic value of high-sensitivity troponin T (hs-TnT) before treatment start has never been investigated.
Thirty consecutive patients underwent measurement of hs-TnT before starting ICI therapy (pembrolizumab, 23%; nivolumab, 12%; atezolizumab, 6%; durvalumab, 5%). The primary endpoint of cardiovascular death, stroke or transient ischaemic attack, pulmonary embolism and new-onset heart failure, and the secondary endpoint of progression of cardiac involvement according to the CARDIOTOX classification were evaluated after 3months from the first cycle.
Patients (median age 68years, 77% men, 13% with coronary artery disease, 90% current or former smokers, 67% overweight or obese and 43% hypertensive) had a median hs-TnT of 12ng/L (interquartile interval 8-23). The primary endpoint occurred only in patients with hs-TnT≥14ng/L at baseline. Therefore, only patients who had hs-TnT≥14ng/L before the first cycle died had a stroke/TIA or new-onset HF. Furthermore, nine out of 13 patients with the secondary endpoint (progression of cardiac disease) had hs-TnT≥14ng/L before the first cycle (P=.012). AUC values were 0.909 for the primary endpoint and 0.757 for the secondary endpoint. The best cut-off was 14ng/L for both the primary (100% sensitivity, 73% specificity) and secondary endpoints (sensitivity 75%, specificity 77%).
In patients on ICIs, baseline hs-TnT predicts a composite cardiovascular endpoint and the progression of cardiac involvement at 3months, with 14ng/L as the best cut-off.
In patients on ICIs, baseline hs-TnT predicts a composite cardiovascular endpoint and the progression of cardiac involvement at 3 months, with 14 ng/L as the best cut-off.Immune checkpoint inhibitors (ICIs) have improved survival for multiple malignancies in adults and children.1,2 However, their benefits are tempered by a range of serious immune-related adverse events (irAEs). 1,2 Among these, cutaneous irAEs (cirAEs) represent one of the most common subtypes, impacting approximately one-third of adult patients receiving ICIs.1,3 The patterns and significance of cirAEs in children remain unclear, largely because these reactions have not been evaluated in detail.
Follistatin-like protein-1 (FSTL-1) is considered to be an adipokine or myokine that could be a potential regulator of metabolism. Our purpose is to investigate the relationship between circulating FSTL-1 levels and insulin resistance (IR) in type 2 diabetes mellitus (T2DM) and to identify the regulatory factors.
FSTL-1 expression in C57BL/6J and db/db mice was examined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blots. Serum FSTL-1 levels were measured by enzyme-linked immunosorbent assay in 298 T2DM patients and 202 healthy controls. Changes in the circulating FSTL-1 level were observed during the oral glucose tolerance test, EHC (euglycemic-hyperinsulinemic clamp), lipid infusion, acute exercise, and cold-exposure test.
We found that FSTL-1 protein expression in the adipose tissue of db/db mice was significantly higher than that of wild-type mice. Importantly, circulating FSTL-1 levels in T2DM and overweight/obese participants were higher than those in healthy and lean individuals, and was related to HOMA-IR, adiponectin, and obesity- and metabolism-related parameters. In the intervention study, 45 minutes of physical activity was found to significantly increase the circulating FSTL-1 concentration in young, healthy participants. Further, FSTL-1 protein expression in adipose tissue rose dramatically in response to physical activity in mice. Hyperinsulinemia during EHC and acute elevated FFA induced by lipid infusion resulted in a significant decrease in the circulating FSTL-1 levels. However, no change was found in the circulating FSTL-1 levels in response to the oral glucose challenge or cold-exposure test.
FSTL-1 may be an adipomyokine associated with insulin resistance and physical activity, and circulating FSTL-1 levels are increased in patients with T2DM.
FSTL-1 may be an adipomyokine associated with insulin resistance and physical activity, and circulating FSTL-1 levels are increased in patients with T2DM.
Widespread technological changes, like the rapid uptake of telehealth in the US during the COVID-19 pandemic, risk creating or widening racial/ethnic disparities. We conducted a secondary analysis of a cross-sectional, nationally representative survey of internet users to evaluate whether there were racial/ethnic disparities in self-reported telehealth use early in the pandemic.
The Pew Research Center fielded the survey March 19-24, 2020. Telehealth use because of the pandemic was measured by asking whether respondents (N = 10624) "used the internet or e-mail to connect with doctors or other medical professionals as a result of the coronavirus outbreak." We conducted survey-weighted logistic regressions, adjusting for respondents' socioeconomic characteristics and perceived threat of the pandemic to their own health (eg, no threat, minor, major).
Approximately 17% of respondents reported using telehealth because of the pandemic, with significantly higher unadjusted odds among Blacks, Latinos, and thoses postpandemic.A key objective of health promotion capacity building and professional development programmes is to enhance competencies in the workforce or training participants. The goal of this study was to investigate and validate the psychometric properties of a recently developed self-assessment tool, based on 'The CompHP core competencies framework for health promotion', to establish whether it is suitable for evaluating training. The tool was employed in 2018 to evaluate two different programmes, with 584 participants submitting their assessment and evaluation of 77 different health promotion training courses in a paper and pencil questionnaire. Longitudinal data were available for 148 participants in the programme for workplace health promotion because they completed an online questionnaire beforehand. The reliability and validity of the assessment tool were tested in several confirmatory factor analyses and structural equation models. Structurally, there was a significant increase in health promotion competencies when comparing measurements before and after training. find more Furthermore, participants were shown to have different levels of competencies due to their prior knowledge, the format of the course or the professional development programme attended but not based on gender, age or sector. The results justify the creation of an overall scale to assess core health promotion competencies that are suitable for evaluating training courses. However, various methodological issues need to be considered in future applications including decisions about the design of the study (e.g. pre-post test, control groups), type of measurements (e.g. general and specific instrument, background information) and depth of analysis (e.g. confirmatory model and invariance testing).Malnutrition suppresses reproductive functions in mammals, which is considered to be mostly due to the inhibition of pulsatile gonadotropin-releasing hormone (GnRH)/gonadotropin secretion. Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC) play a critical role in the regulation of pulsatile GnRH/gonadotropin release. The present study aimed to examine if the hypothalamic dynorphin A (Dyn) neurons mediate the suppression of GnRH/luteinizing hormone (LH) pulses during malnutrition. Ovariectomized rats treated with a negative feedback level of estradiol-17β-treated (OVX+E2) were administered with intravenous (iv) or fourth cerebroventricle (4V) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, to serve as a malnutrition model. Central administration of a Dyn receptor antagonist blocked the iv- or 4V-2DG-induced suppression of LH pulses in OVX+E2 rats. The 4V 2DG administration significantly increased the number of Pdyn (Dyn gene)-positive cells co-expressing fos in the paraventricular nucleus (PVN), but not in the ARC and supraoptic nucleus (SON), and the iv 2DG treatment significantly increased the number of fos and Pdyn-co-expressing cells in the PVN and SON, but decreased it in the ARC. The E2 treatment significantly increased Pdyn expression in the PVN, but not in the ARC and SON. Double in situ hybridization for Kiss1 (kisspeptin gene) and Oprk1 (Dyn receptor gene) revealed that around 60% of ARC Kiss1-expressing cells co-expressed Oprk1. These results suggest that the PVN Dyn neurons, at least in part, mediate LH pulse suppression induced by the hindbrain or peripheral glucoprivation, and Dyn neurons may directly suppress the ARC kisspeptin neurons in female rats.Dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyl-dichloroethylene (DDE) are ubiquitously found in the environment and linked to cardiovascular diseases-with a majority of the work focused on hypertension. Studies investigating whether DDx can interact with molecular targets on cardiac tissue to directly affect cardiac function are lacking. Therefore, we investigated whether o,p'-DDT, p,p'-DDT, o,p'-DDE, or p,p'-DDE (DDx, collectively) can directly alter the function of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by assessing their effect(s) on hiPSC-CMs Ca2+ dynamics. DDx (0.1-10 µM) affected hiPSC-CMs synchronous Ca2+ oscillation frequency in a concentration-dependent manner, with p,p'-DDT and p,p'-DDE also decreasing Ca2+ stores. HEK-RyR2 cells cultured under antibiotic selection to induce expression of wild-type mouse ryanodine receptor type 2 (RyR2) are used to further investigate whether DDx alters hiPSC-CMs Ca2+ dynamics through engagement with RyR2, alar outcomes associated with exposures.
The diagnosis of osteoporosis and assessment of fracture risk prior to a sentinel fracture was transformed by the widespread clinical use of dual-energy X-ray absorptiometry (DXA) for the assessment of bone mineral density (BMD).
This review is based on a collection of primary and review literature gathered from a PubMed search of "dual energy X-ray absorptiometry," "trabecular bone score," and "atypical femur fracture" among other keywords. PubMed searches were supplemented by the authors' prior knowledge of the subject.
While uncertainty exists for some aspects of osteoporosis care, patient and clinician familiarity with BMD assessment for screening and monitoring is firmly established. Beyond BMD, lateral spine images obtained with DXA can diagnose osteoporosis and refine fracture risk through the detection of unrecognized vertebral fractures. In addition, analysis of DXA lumbar spine images can reflect changes in trabecular bone microarchitecture, a component of bone "quality" that predicts risk of re providers will be well positioned to contribute to continuous improvement of DXA performance and, in turn, quality of osteoporosis care.Two experiments were conducted to test the hypothesis that the digestibility of gross energy (GE) and nutrients, and concentrations of digestible energy (DE) and metabolizable energy (ME) in two sources of distillers dried grains with solubles (DDGS) are not different despite different concentrations of fat in the two sources. Cold-fermented DDGS (6.82% fat) and a conventional DDGS (9.54% fat) were used. In experiment 1, 12 growing barrows (initial body weight = 55.2 ± 3.6 kg) that had a T-cannula installed in the distal ileum were allotted to one of three diets and two periods. Two diets contained either cold-fermented or conventional DDGS as the sole source of crude protein (CP) and amino acids (AA). The third diet was an N-free diet that was used to determine the basal endogenous losses of AA from the pigs. Each experimental period lasted 7 d and ileal digesta were collected on days 6 and 7 of each period. Results demonstrated that values for the standardized ileal digestibility (SID) of CP and most AA were greater (P less then 0.
