Explore the vast range of titles available.

The aim of this study was to assess the feasibility, safety, and preliminary efficacy of a novel percutaneous left ventricular partitioning device (VPD) in patients with chronic heart failure (HF) and a prior anterior myocardial infarction. Anterior myocardial infarction is frequently followed by left ventricular remodeling, HF, and increased long-term morbidity and mortality. Thirty-nine patients were enrolled in a multinational, nonrandomized, longitudinal investigation. The primary end point was an assessment of safety, defined as the successful delivery and deployment of the VPD and absence of device-related major adverse cardiac events over 6 months. Secondary (exploratory) efficacy end points included changes in hemodynamics and functional status and were assessed serially throughout the study. Ventricular partitioning device placement was not attempted in 5 (13%) of 39 subjects. The device was safely and successfully implanted in 31 (91%) of the remaining 34 patients or 79% of all enrolled patients. The 6-month rate of device-related major adverse cardiac event occurred in 5 (13%) of 39 enrolled subjects and 5 (15%) of 34 treated subjects, with 1 additional event occurring between 6 and 12 months. For patients discharged with the device to 12 months (n = 28), New York Heart Association class (2.5 ± 0.6 to 1.3 ± 0.6, P < .001) and quality-of-life scores (38.6 ± 6.1 to 28.4 ± 4.4, P < .002) improved significantly; however, the 6-minute hall walk distance (358.5 ± 20.4 m to 374.7 ± 25.6 m, P nonsignificant) only trended toward improvement. The left VPD appears to be relatively safe and potentially effective in the treatment for patients with HF and a prior anterior myocardial infarction. However, these limited results suggest the need for further evaluation in a larger randomized controlled trial.

Takotsubo cardiomyopathy, also known as apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome, is a disease characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease. Herein, we present a case in which a heart with mild takotsubo cardiomyopathy was utilized as the donor organ for an orthotopic heart transplant.

Takotsubo cardiomyopathy, also known as apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome, is a disease characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease. Herein, we present a case in which a heart with mild takotsubo cardiomyopathy was utilized as the donor organ for an orthotopic heart transplant.

Among carbon-based nanomaterials, carbon dots (CDs) have received a surge of interest in recent years due to their attractive features such as tunable photoluminescence, cost effectiveness, nontoxic renewable resources, quick and direct reactions, chemical and superior water solubility, good cell-membrane permeability, and simple operation. CDs and their composites have a large potential for sensing contaminants present in physical systems such as water resources as well as biological systems. Tuning the properties of CDs is a very important subject. This review discusses in detail heteroatom doping (N-doped CDs, N-CDs) and the formation of metal-based CD nanocomposites using a combination of matrices, such as metals and metal oxides. The properties of N-CDs and metal-based CDs nanocomposites, their syntheses, and applications in both chemical sensing and biosensing are reviewed.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAM high cells compared to the cisplatin sensitive counterpart. EpCAM high populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAM high populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAM high populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAM high populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAM high populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAM high populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAM high populations.

Background Accurate growth assessment of preterm infants is essential in guiding medical care and suitable nutritional interventions. Currently, different growth references are used across hospitals in the United Arab Emirates (UAE). This study aims to compare the INTERGROWTH-21st standards with Fenton growth references regarding birth size classification and at the time of discharge in a sample of preterm infants in the UAE. Methods A retrospective single-center evaluation of medical records of infants born < 37 weeks of gestation was conducted using data from 2018 to 2020. Anthropometric measurements (weight, length, and head circumference) were obtained at birth and at the time of discharge, and then converted to percentiles according to the two reference standards. Results A total of 1537 infants with a median birth gestation of 35.3 weeks, and a median birthweight of 2320 g were included. The rates of SGA, AGA, and LGA at birth were 11.5%, 80.42%, and 9.08% using INTERGROWTH-21st growth charts compared to 9.5%, 83.2%, and 7.3% respectively according to Fenton charts. The findings indicated statistically significant differences between the two growth charts classifying of preterm infants based on weight, length, and head circumference ( p  < 0.05). For every 5 cases assessed as SGA at discharge according to Fenton charts, only 3 were classified as SGA by INTERGROWTH-21st curves. Conclusions Differences exist between the two growth charts with only moderate agreement. Thus, there is a need for harmonizing growth assessment standards. Misclassification of these vulnerable infants would affect their in-hospital and post-discharge nutrition and medical care plan.

Background The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes. Methods The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15–35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12–14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI) < 18.5 kg/m 2 and MMS for others; (4) targeted BEP for those with pre-pregnancy BMI < 18.5 kg/m 2 , MMS for others, and women with inadequate gestational weight gain switched from MMS to BEP until the end of pregnancy. Primary outcomes include birth weight, low birth weight (< 2500 g), and small for gestational age, defined using the 10 th percentile of the INTERGROWTH-21st reference, for live-born infants measured within 72 h of birth. Project-hired local female staff visit pregnant women monthly to deliver the assigned supplements, monitor adherence biweekly, and assess weight regularly during pregnancy. Trained data collectors conduct pregnancy outcome assessment and measure newborn anthropometry in the facility or home depending on the place of birth. Discussion This study will assess the effectiveness of targeted balanced energy and protein supplementation to improve birth outcomes among pregnant women in rural Bangladesh and similar settings. Trial registration ClinicalTrials.gov NCT05576207. Registered on October 5th, 2022.

BackgroundOur objective was to assess the performance of machine learning methods to predict post-operative delirium using a prospective clinical cohort.MethodsWe analyzed data from an observational cohort study of 560 older adults (≥ 70 years) without dementia undergoing major elective non-cardiac surgery. Post-operative delirium was determined by the Confusion Assessment Method supplemented by a medical chart review (N = 134, 24%). Five machine learning algorithms and a standard stepwise logistic regression model were developed in a training sample (80% of participants) and evaluated in the remaining hold-out testing sample. We evaluated three overlapping feature sets, restricted to variables that are readily available or minimally burdensome to collect in clinical settings, including interview and medical record data. A large feature set included 71 potential predictors. A smaller set of 18 features was selected by an expert panel using a consensus process, and this smaller feature set was considered with and without a measure of pre-operative mental status.ResultsThe area under the receiver operating characteristic curve (AUC) was higher in the large feature set conditions (range of AUC, 0.62–0.71 across algorithms) versus the selected feature set conditions (AUC range, 0.53–0.57). The restricted feature set with mental status had intermediate AUC values (range, 0.53–0.68). In the full feature set condition, algorithms such as gradient boosting, cross-validated logistic regression, and neural network (AUC = 0.71, 95% CI 0.58–0.83) were comparable with a model developed using traditional stepwise logistic regression (AUC = 0.69, 95% CI 0.57–0.82). Calibration for all models and feature sets was poor.ConclusionsWe developed machine learning prediction models for post-operative delirium that performed better than chance and are comparable with traditional stepwise logistic regression. Delirium proved to be a phenotype that was difficult to predict with appreciable accuracy.

Background: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs). Methods: We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated. Results: Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC. Conclusions: These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.

IntroductionAntenatal corticosteroid (ACS) regimens have remained unchanged since the initial trials in 1972, with the optimal regimen still undetermined. The WHO ACTION (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns)-III trial is a three-arm individually randomised double-blind trial evaluating the efficacy and safety of two different ACS dosing regimens (currently used and lower-dose ACS regimens vs placebo) in women with a high probability of having a late preterm birth. This study protocol nested within this trial aims to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) effects of two different ACS dosing regimens in pregnant women in the late preterm period (34–36 weeks) to help inform an optimal dosing regimen.Methods and analysisThe study will be conducted in two of the five countries participating in the WHO ACTION-III trial—India (Delhi, Belagavi) and Nigeria (Ibadan and Ile-Ife). We will use a population PK approach using sparse sampling to study the PK effects of the two ACS regimens, that is, 6 mg dexamethasone phosphate (DEXp) or 2 mg betamethasone phosphate (BETp), administered intramuscularly every 12 hours for a maximum of four doses or till birth, whichever is earlier, compared with placebo. We will also ascertain the fetal–maternal ratio of DEXp and BETp at birth.Maternal venous blood samples will be collected at 0, 1–4 hours, 8–12 hours after the first dose, and at 24–36 hours, 48–60 hours, 72–96 hours after the last dose, and immediately after birth, along with cord blood. Concentrations of DEXp and BETp will be measured at set time points using a validated liquid chromatography mass spectroscopy assay. PD parameters measured will include total and differential white blood cell count (by automated analysers using electrical impedance), plasma glucose (hexokinase method) and serum cortisol (using a validated electrochemiluminescence immunoassay), at predefined time points. PK models will be developed for each drug using non-linear mixed effects methods. Optimal dosing will be investigated using Monte Carlo simulations.Ethics and disseminationThe study has been approved by the WHO Ethics Review Committee and the site-specific ethics committees of the participating leading institutions. Written informed consent will be obtained from all participants. The study results will be published in a peer-reviewed journal and presented at scientific conferences.Trial registration numberISRCTN11434567.