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Metabolic syndrome (MetS) induces a systemic inflammatory state which can lead to cardiomyopathy, manifesting clinically as heart failure (HF) with preserved ejection fraction (HFpEF). MetS components are intricately linked to the pathophysiologic processes of myocardial remodeling. Increased sympathetic nervous system activity, which is noted as an upstream factor of MetS, has been linked to adverse myocardial structural changes. Since renal denervation and vagus nerve stimulation have a sympathoinhibitory effect, attention has been paid to the cardioprotective effects of autonomic neuromodulation. In this review, the pathophysiology underlying the relationship between MetS and HF is elucidated, and the evidence regarding autonomic neuromodulation in HFpEF is summarized.

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BACKGROUND: Presurgical blood orders are important for patient safety during surgery, but excess orders can be costly to patients and the healthcare system. We aimed to assess clinician perceptions on the presurgical blood ordering process and perceived barriers to reliable decision-making. METHODS: This descriptive qualitative study was conducted at a single large academic medical center. Semi-structured interviews were conducted with surgeons, anesthesiologists, nurse anesthetists, nurse practitioners working in preoperative assessment clinics, and transfusion medicine physicians to assess perceptions of current blood ordering processes. Interview responses were analyzed using an inductive open coding approach followed by thematic analysis. RESULTS: Twenty-three clinicians were interviewed. Clinicians felt that the current blood ordering process was frequently inconsistent. One contributor was a lack of information on surgical transfusion risk, related to lack of experience in ordering clinicians, insufficient communication between stakeholders, high turnover in academic settings, and lack of awareness of the maximum surgical blood ordering schedule. Other contributors included differing opinions about the benefits and harms of over- and under-preparing blood products, leading to variation in transfusion risk thresholds between clinicians, and disagreement about the safety of emergency-release blood. CONCLUSION: Several barriers to reliable decision-making for presurgical blood orders exist. Future efforts to improve ordering consistency may benefit from improved information sharing between stakeholders and education on safe transfusion practices.

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BACKGROUND: Improving the quality of breastfeeding counselling delivered by primary care providers can improve breastfeeding outcomes and ultimately reduce mortality and morbidity of children and mothers. Accurate data on coverage and quality of primary care breastfeeding counselling is essential for monitoring progress; however, global and national indicators are limited. To help address this gap, this study validated indicators of receipt and quality of breastfeeding counselling during routine consultations for infant care at seven primary health facilities across Kosovo. METHODS: Mothers' reports of breastfeeding counselling received during routine consultations for their infants (0-12 months of age) were collected by exit interview in 2019 and 2021 (n = 609). Responses were compared against direct observation of their consultation using a structured checklist (reference standard) by a trained third-party observer at the primary care facility. We assessed 13 indicators; ten were related to the receipt and content of breastfeeding counselling, and three were specific to the provider's interpersonal skills. We calculated sensitivity, specificity, and area under the receiver operating curve (AUC) to determine individual-level reporting accuracy. RESULTS: Ten indicators had an agreement rate above 70% and seven indicators had high overall individual-level validity (AUC ≥ 0.7). High prevalence indicators recorded high sensitivity and low specificity, and the inverse for low prevalence indicators. More subjective indicators were less reliable, e.g., mothers over-reported the prevalence of all three indicators related to providers' interpersonal skills. CONCLUSIONS: This study offers evidence on breastfeeding counselling quality by validating maternal reports of whether a provider discussed breastfeeding, the clinical content of that counselling, and how it was delivered. It is also situated in a primary care setting within a fragile state of which there is limited evidence. We observed that mothers reported accurately when asked directly to recall breastfeeding counselling services received. However, there is a need to further validate subjective questions about interpersonal skills and other measures for the 'experience of care' quality dimension.

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INTRODUCTION: The interaction between the cardiovascular and respiratory systems in healthy subjects is determined by the autonomic nervous system and reflected in respiratory sinus arrhythmia. Recently, another pattern of cardio-respiratory coupling (CRC) has been proposed linking synchronization of heart and respiratory system. However, CRC has not been studied precisely in heart failure (HF) with reduced ejection fraction (EF) (HFrEF) according to the myocardial recovery. METHODS: 10-min resting electrocardiography measurements were performed in persistent HFrEF patients (n=40) who had a subsequent left ventricular EF (LVEF) of ≤ 40 %, HF with recovered EF patients (HFrecEF) (n=41) who had a subsequent LVEF of > 40 % and healthy controls (n=40). Respiratory frequency, respiratory rate, CRC index, time-domain, frequency-domain and nonlinear heart rate variability indices were obtained using standardized software-Kubios™. CRC index was defined as respiratory high-frequency peak minus heart rate variability high-frequency peak. RESULTS: Respiratory rate was positively correlated with high-frequency (HF) peak (Hz) in both persistent HFrEF group (p<0.001) and HFrecEF group (p<0.001), while respiratory rate was negatively correlated with HF power (ms2) in the healthy controls (p<0.05). CRC index was lowest in the persistent HFrEF group followed by HFrecEF and was high in healthy controls (0.008 vs 0.012 vs 0.056 Hz, p=0.03). CONCLUSION: CRC index was lowest in patients with impaired myocardial recovery, which indicates that cardio-respiratory synchrony is stronger in persistent HFrEF. This may represent a higher HF peak (Hz)/lower HF power (ms2) and abnormal sympathovagal balance in persistent HFrEF group compared to healthy controls. Further work is underway to tests this hypothesis and determine the utility of CRC index in HF phenotypes and its utility as a potential biomarker of response with neuromodulation.

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The autonomic nervous system plays a central role in the pathogenesis of arrhythmias. Preclinical and clinical studies have demonstrated the therapeutic effect of neuromodulation at multiple anatomic targets across the neurocardiac axis for the treatment of arrhythmias. In this review, we discuss the rationale and clinical application of noninvasive neuromodulation techniques in treating arrhythmias and explore associated barriers and future directions, including optimization of stimulation parameters and patient selection.

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OBJECTIVES: To develop and validate a novel measure, action entropy, for assessing the cognitive effort associated with electronic health record (EHR)-based work activities. MATERIALS AND METHODS: EHR-based audit logs of attending physicians and advanced practice providers (APPs) from four surgical intensive care units in 2019 were included. Neural language models (LMs) were trained and validated separately for attendings' and APPs' action sequences. Action entropy was calculated as the cross-entropy associated with the predicted probability of the next action, based on prior actions. To validate the measure, a matched pairs study was conducted to assess the difference in action entropy during known high cognitive effort scenarios, namely, attention switching between patients and to or from the EHR inbox. RESULTS: Sixty-five clinicians performing 5 904 429 EHR-based audit log actions on 8956 unique patients were included. All attention switching scenarios were associated with a higher action entropy compared to non-switching scenarios (P < .001), except for the from-inbox switching scenario among APPs. The highest difference among attendings was for the from-inbox attention switching: Action entropy was 1.288 (95% CI, 1.256-1.320) standard deviations (SDs) higher for switching compared to non-switching scenarios. For APPs, the highest difference was for the to-inbox switching, where action entropy was 2.354 (95% CI, 2.311-2.397) SDs higher for switching compared to non-switching scenarios. DISCUSSION: We developed a LM-based metric, action entropy, for assessing cognitive burden associated with EHR-based actions. The metric showed discriminant validity and statistical significance when evaluated against known situations of high cognitive effort (ie, attention switching). With additional validation, this metric can potentially be used as a screening tool for assessing behavioral action phenotypes that are associated with higher cognitive burden. CONCLUSION: An LM-based action entropy metric-relying on sequences of EHR actions-offers opportunities for assessing cognitive effort in EHR-based workflows.

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OBJECTIVES: Electronic health record (EHR)-integrated secure messaging is extensively used for communication between clinicians. We investigated the factors contributing to secure messaging use in a large health care system. METHODS: This was a cross-sectional study that included 14 hospitals and 263 outpatient clinic locations. Data on EHR-integrated secure messaging use over a 1-month period (February 1, 2023, through February 28, 2023) were collected. A multilevel mixed effects model was used to assess the contribution of clinical role, clinical unit (i.e., specific inpatient ward or outpatient clinic), hospital or clinic location (i.e., Hospital X or Outpatient Clinic Building Y), and inpatient versus outpatient setting toward secure messaging use. RESULTS: Of the 33,195 health care professionals who worked during the study period, 20,576 (62%) were secure messaging users. In total, 25.3% of the variability in messaging use was attributable to the clinical unit and 30.5% was attributable to the hospital or clinic location. Compared with nurses, advanced practice providers, pharmacists, and physicians were more likely to use secure messaging, whereas medical assistants, social workers, and therapists were less likely (p < 0.001). After adjusting for other factors, inpatient versus outpatient setting was not associated with secure messaging use. CONCLUSION: Secure messaging was widely used; however, there was substantial variation by clinical role, clinical unit, and hospital or clinic location. Our results suggest that interventions and policies for managing secure messaging behaviors are likely to be most effective if they are not only set at the organizational level but also communicated and tailored toward individual clinical units and clinician workflows.

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Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days. In the active group, standard deviation (SD), coefficient of variation (CV) and δ in SBP were significantly decreased after LLTS (all p < 0.05). All the changes in SD, CV and δ in SBP before and after stimulation were also significantly different between active and sham groups (all p < 0.05). This proof-of-concept study demonstrates the beneficial effects of LLTS on BPV in AHF.

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Diabetes mellitus (DM) confers an increased risk of sudden cardiac death (SCD) independent of its associated cardiovascular comorbidities. DM induces adverse structural, electrophysiologic, and autonomic cardiac remodeling that can increase one's risk of ventricular arrhythmias and SCD. Although glycemic control and prevention of microvascular and macrovascular complications are cornerstones in the management of DM, they are not adequate for the prevention of SCD. In this narrative review, we describe the contribution of DM to the pathophysiologic mechanism of SCD beyond its role in atherosclerotic cardiovascular disease and heart failure. On the basis of this pathophysiologic framework, we outline potential preventive and therapeutic strategies to mitigate the risk of SCD in this population of high-risk patients.

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Successful heart development depends on the careful orchestration of a network of transcription factors and signaling pathways. In recent years, in vitro cardiac differentiation using human pluripotent stem cells (hPSCs) has been used to uncover the intricate gene-network regulation involved in the proper formation and function of the human heart. Here, we searched for uncharacterized cardiac-development genes by combining a temporal evaluation of human cardiac specification in vitro with an analysis of gene expression in fetal and adult heart tissue. We discovered that CARDEL (CARdiac DEvelopment Long non-coding RNA; LINC00890; SERTM2) expression coincides with the commitment to the cardiac lineage. CARDEL knockout hPSCs differentiated poorly into cardiac cells, and hPSC-derived cardiomyocytes showed faster beating rates after controlled overexpression of CARDEL during differentiation. Altogether, we provide physiological and molecular evidence that CARDEL expression contributes to sculpting the cardiac program during cell-fate commitment.

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This cohort study investigates the association of use of text-based secured messaging with telephone use among resident physicians.

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INTRODUCTION: B cell exhaustion is a functional abnormality of B lymphocytes observed in chronic infections and shows association with autoreactivity. The role of exhausted and classical memory B cells in maintaining disease stability of lupus nephritis (LN) remains unclear. METHODS: We measured classical memory (CD19+CD21+CD27+), exhausted B cells (CD19+CD21-CD27-), and related cytokines in LN patients with multiple relapses (MR) (n = 15) and no relapse (NR) (n = 15) during disease remission. The expression of inhibitory/adhesion molecules, cell proliferation and calcium mobilization in classical memory and exhausted B cells were also assessed. RESULTS: The MR group had higher proportion of circulating exhausted and classical memory B cells compared to the NR group and healthy controls (HC) (p all <0.05 for MR vs. NR or HC). Blood levels of IL-6, BAFF, IL-21, CD62L, CXCR3 and Siglec-6 were all higher in the MR group (p < 0.05, for all). Exhausted B cells from the MR group showed higher FcRL4, CD22, CD85j and CD183 but lower CD62L expression than NR and HC groups. Exhausted B cells from MR patients exhibited reduced proliferation compared to NR patients and HC, while classical memory B cell proliferation in MR group was higher than the other two groups. Exhausted B cells from both MR and NR patients showed impaired calcium mobilization. CONCLUSION: Alterations in exhausted and classical memory B cells are related to disease relapse in LN. These findings may help devise new strategies for monitoring disease activity and preventing relapse in LN.

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This study was intended to evaluate the pathological outcome of cardiopulmonary bypass whilst considering socio-demographic variables and surgical technique on early postoperative results following coronary artery bypass graft (CABG) surgery in patients at a tertiary level hospital in Bangladesh. This observational study evaluated a total of 880 patients with ischemic heart disease in Bangabandhu Sheikh Mujib Medical University, Bangladesh from 2011 to 2019 who were undergoing an isolated CABG surgery. In this current study, the population divided into two groups- Group A: Off-pump CABG (n=440) and Group B: On-pump CABG (n=440). The mean age of the patients was 55.25±5.0 years in off-pump and 50.75±5.2 years in the on-pump group. Risk factors, including smoking, hypertension, and hyperlipidemia, were predominant in both study groups. Total operative time was notably higher in the on-pump CABG group. However, grafting time was more in the off-pump CABG procedures. Postoperative neurological deficits were higher amongst the on-pump CABG population. The mean time of mechanical ventilation, intensive care unit (ICU) stay, total hospital stay, and mortality was notably higher in the on-pump CABG group. Moreover, the number of mortalities in on-pump CABG patients was primarily due to the low output syndrome, failure of weaning from cardiopulmonary bypass (CPB) and sudden cardiac arrest. Off-pump CABG is now more acceptable due to its potentiality to avoid CPB induced complications, aortic cannulation, and cross-clamping. Cardiac arrest in on-pump CABG induces global ischemia and reperfusion injury to the cardiac muscle. Besides, the Off-pump CABG provides a conspicuous survival advantage compared to the on-pump CABG, in association with a notable reduction in postoperative morbidity and mortality.

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OBJECTIVES: Cardiotoxic chemotherapy is used to treat malignancies such as breast cancer and lymphoma. These treatments predispose patients to cardiotoxicity that can lead to cancer treatment-related cardiac dysfunction (CTRCD). The use of high doses of anthracyclines or in combination with human epidermal growth factor receptor 2 antagonists is associated with a progressively higher risk of CTRCD. CTRCD is preceded by increased activation of the sympathetic nervous system and abnormal left ventricular mechanical deformation as measured by abnormal global longitudinal strain (GLS). Low-level tragus stimulation (LLTS) is a new, safe, noninvasive technique that offers great potential to reduce increased sympathetic activation and improve GLS. Here, we describe a study method to examine the effects of LLTS on autonomic balance and cardiac function in breast cancer or lymphoma patients treated with anthracyclines. METHODS: A first-in-human pilot, randomized, double-blind feasibility study will evaluate 104 patients (age >50 y) with breast cancer or lymphoma who receive anthracyclines with one additional CTRCD risk factor. Patients undergo 2 weeks of LLTS daily (1 h/d). Autonomic balance will be measured using heart rate variability metrics. Strain imaging using GLS will be performed pre and post-LLTS. Endothelial inflammation and oxidative stress measures will be performed using in vitro assays at baseline and after 2 weeks. CONCLUSION: We hypothesize that LLTS stabilizes sympathovagal imbalance and improves cardiac performance in anthracycline-treated patients with breast cancer or lymphoma.

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[This corrects the article DOI: 10.1016/j.cdnut.2023.102053.].

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Producing an adequate number of muscle stem cells (MuSCs) with robust regenerative potential is essential for the successful cell therapy of muscle-wasting disorders. We have recently developed a method to produce skeletal myogenic cells with exceptional engraftability and expandability through an in vivo pluripotent stem cell (PSC) differentiation approach. We have subsequently mapped engraftment and gene expression and found that leukemia inhibitory factor receptor (Lifr) expression is positively correlated with engraftability. We therefore investigated the effect of LIF, the endogenous ligand of LIFR, on cultured MuSCs and examined their engraftment potential. We found that LIF-treated MuSCs exhibited elevated expression of PAX7, formed larger colonies from single cells, and favored the retention of PAX7+ "reserve cells" upon myogenic differentiation. This suggested that LIF promoted the maintenance of cultured MuSCs at a stem cell stage. Moreover, LIF enhanced the engraftment capability of MuSCs that had been expanded in vitro for 12 days by 5-fold and increased the number of MuSCs that repopulated the stem cell pool post-transplantation. These results thereby demonstrated the effectiveness of our in vivo PSC differentiation platform to identify positive regulators of the engraftability of cultured MuSCs.

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High intakes of sodium, sugar, saturated fats, and trans-fats contributed to 187.7 million disability adjusted life years from noncommunicable diseases globally. Understanding of the global evidence on interventions to reduce consumption of various types of unhealthy food across diverse contexts is needed. We conducted a scoping review to examine the existing evidence on behavior change interventions (BCIs) to address unhealthy food consumption. Through a systematic search of 3 databases conducted in December 2022, 2730 records were retrieved, and 145 studies met the eligibility criteria for review. Only 19% of the studies (n = 28) were from low- and middle-income countries. The key target group for most BCIs was adults ≥20 y (n = 79). Interventions were conducted across 7 types of settings: schools (n = 52), digital (n = 30), community (n = 28), home (n = 14), health facility (n = 12), worksite (n = 6), and market (n = 3). There were 4 mutually inclusive intervention types-information, education, and communication (n = 141); food/beverage substitution (n = 10); interactive games (n = 7); and labeling/warnings at point-of-purchase (n = 3). The study outcomes included consumption of sugar-sweetened beverages (n = 74), packaged salty snacks/fast food (n = 61), sweets (n = 43), and saturated fat (n = 41). Drivers of food choice behaviors, such as knowledge, attitudes, and beliefs; motivation and expectancies; and self-efficacy were reported in 43% of studies. On the basis of reported impact of BCIs on study outcomes, more interventions targeted at adults had positive impacts compared with those targeted at children; intervention packages, including multiple information, education, and communication components also reported impacts more often than single informational interventions. Interpretation of the findings was complicated by the lack of comparability in interventions, evaluation designs, outcome measures of unhealthy food consumption, duration of interventions, and study contexts. Future studies should invest in critical yet underrepresented regions, examine behavioral determinants of unhealthy food consumption and the sustainability of behavior change, and conduct further analysis of effectiveness from experimental studies.

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Human induced pluripotent stem cells and their differentiation into cardiac myocytes (hiPSC-CMs) provides a unique and valuable platform for studies of cardiac muscle structure-function. This includes studies centered on disease etiology, drug development, and for potential clinical applications in heart regeneration/repair. Ultimately, for these applications to achieve success, a thorough assessment and physiological advancement of the structure and function of hiPSC-CMs is required. HiPSC-CMs are well noted for their immature and sub-physiological cardiac muscle state, and this represents a major hurdle for the field. To address this roadblock, we have developed a hiPSC-CMs (ß-MHC dominant) experimental platform focused on directed physiological enhancement of the sarcomere, the functional unit of cardiac muscle. We focus here on the myosin heavy chain (MyHC) protein isoform profile, the molecular motor of the heart, which is essential to cardiac physiological performance. We hypothesized that inducing increased expression of α-MyHC in ß-MyHC dominant hiPSC-CMs would enhance contractile performance of hiPSC-CMs. To test this hypothesis, we used gene editing with an inducible α-MyHC expression cassette into isogeneic hiPSC-CMs, and separately by gene transfer, and then investigated the direct effects of increased α-MyHC expression on hiPSC-CMs contractility and relaxation function. Data show improved cardiac functional parameters in hiPSC-CMs induced with α-MyHC. Positive inotropy and relaxation was evident in comparison to ß-MyHC dominant isogenic controls both at baseline and during pacing induced stress. This approach should facilitate studies of hiPSC-CMs disease modeling and drug screening, as well as advancing fundamental aspects of cardiac function parameters for the optimization of future cardiac regeneration, repair and re-muscularization applications.

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