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Abstract 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.

Abstract 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 (β-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 β-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 β-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.

Abstract Background The autonomic nervous system can be responsible for the initiation and maintenance of arrhythmias. Low-level tragus stimulation (LLTS), a noninvasive form of autonomic neuromodulation, has been shown to be effective in treating atrial fibrillation. We intended to treat frequent premature ventricular complexes (PVCs) with LLTS. Methods and design The present study will be a prospective multicenter, double-blind, randomized, controlled trial to assess the antiarrhythmic effects of LLTS on frequent PVCs in patients without structured heart disease (SHD). A total of 100 patients with PVC burden > 10% will be randomly assigned to the active or sham LLTS in 1:1 fashion and receive the proposed intervention for 6 months. The primary outcome is PVC burden at 6 months as assessed by 10 days of continuous ambulatory electrocardiographic monitoring. Secondary outcomes include heart rate variability (HRV), quality of life, skin sympathetic nerve activity, and inflammatory markers. Adverse events will also be recorded. Discussion The present trial will be the first to evaluate the effect of LLTS on frequent PVCs on patients without SHD. LLTS may serve as a low-cost, minimal-risk, and non-invasive alternative to conventional antiarrhythmic therapy. Trial registration ClinicalTrial.gov NCT04909528. Registered on 17 June 2021. World health organization trial registration data set was shown in Supplementary Table 1.

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.

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.

Background Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high‐risk patients is important but labor‐intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. Methods and Results We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI‐based tool for subsequent AF detection using ECG records alone. A total of 5 million 30‐second epochs from 329 patients were annotated as AF or non‐AF by expert ECG readers for AI training and validation, while 5 million 30‐second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. Conclusions Use of both atrial electrograms and surface ECG permitted development of a robust AI‐based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

Abstract Progress to improve nutrition among women, infants and children in South Asia has fallen behind the pace needed to meet established global targets. Renewed political commitment and monitoring of nutrition interventions are required to improve coverage and quality of care. Our study aimed to assess the availability of national nutrition policies, programmes, and coverage data of nutrition interventions for women, children, and adolescents in eight countries in South Asia. We reviewed relevant policy and programme documents, examined questionnaires used in the most recent rounds of 20 nationally representative surveys, and generated an evidence gap map on the availability of policies, programmes, and survey data to track progress on coverage of globally recommended nutrition interventions. Current policies and programmes in South Asian countries addressed almost all the recommended nutrition interventions targeted at women, children, and adolescents. There was a strong policy focus in all countries, except Maldives, on health system platforms such as antenatal and postnatal care and child growth and development. Survey data on nutrition intervention coverage was most available in India and Nepal, while Bangladesh and Bhutan had the least. Though countries in South Asia have committed to national nutrition policies and strategies, national surveys had substantial data gaps, precluding progress tracking of nutrition intervention coverage. Greater attention and effort are needed for multisectoral collaboration to promote and strengthen nutrition data systems.

BackgroundCommunication among health care professionals is essential for the delivery of safe clinical care. Secure messaging has rapidly emerged as a new mode of asynchronous communication. Despite its popularity, relatively little is known about how secure messaging is used and how such use contributes to communication burden. ObjectiveThis study aims to characterize the use of an electronic health record–integrated secure messaging platform across 14 hospitals and 263 outpatient clinics within a large health care system. MethodsWe collected metadata on the use of the Epic Systems Secure Chat platform for 6 months (July 2022 to January 2023). Information was retrieved on message volume, response times, message characteristics, messages sent and received by users, user roles, and work settings (inpatient vs outpatient). ResultsA total of 32,881 users sent 9,639,149 messages during the study. Median daily message volume was 53,951 during the first 2 weeks of the study and 69,526 during the last 2 weeks, resulting in an overall increase of 29% (P=.03). Nurses were the most frequent users of secure messaging (3,884,270/9,639,149, 40% messages), followed by physicians (2,387,634/9,639,149, 25% messages), and medical assistants (1,135,577/9,639,149, 12% messages). Daily message frequency varied across users; inpatient advanced practice providers and social workers interacted with the highest number of messages per day (median 19). Conversations were predominantly between 2 users (1,258,036/1,547,879, 81% conversations), with a median of 2 conversational turns and a median response time of 2.4 minutes. The largest proportion of inpatient messages was from nurses to physicians (972,243/4,749,186, 20% messages) and physicians to nurses (606,576/4,749,186, 13% messages), while the largest proportion of outpatient messages was from physicians to nurses (344,048/2,192,488, 16% messages) and medical assistants to other medical assistants (236,694/2,192,488, 11% messages). ConclusionsSecure messaging was widely used by a diverse range of health care professionals, with ongoing growth throughout the study and many users interacting with more than 20 messages per day. The short message response times and high messaging volume observed highlight the interruptive nature of secure messaging, raising questions about its potentially harmful effects on clinician workflow, cognition, and errors.

Abstract Agricultural development projects increasingly aim to improve health and nutrition outcomes, often by engaging women. Although evidence shows such projects can improve women's and children's health and nutrition and empower women, little is known about their impacts on women's health‐ and nutrition‐related agency and the extent to which impacts emerge through women's empowerment, largely due to a lack of instruments that measure the dimensions of women's agency that are directly relevant to health and nutrition outcomes. We developed an optional, complementary module for the project‐level women's empowerment in agriculture index (pro‐WEAI) to measure health‐ and nutrition‐related agency (pro‐WEAI + HN). Our method for developing related indicators used data collected from six agricultural development programmes implemented across Bangladesh, Burkina Faso and Mali (pooled sample = 12,114) and applied psychometric analysis (exploratory and confirmatory factor analysis) and the Alkire−Foster methodology. Results revealed seven indicators covering women's agency in the areas of her own health and diet; her health and diet during pregnancy; her child's diet; breastfeeding and weaning; purchasing food and health products; and acquiring food and health products. Multigroup confirmatory factor analysis revealed measurement invariance across contexts and samples. Tests of association (Cramer's V) and redundancy suggest that the pro‐WEAI + HN indicators measured aspects of agency that are distinct from the core pro‐WEAI. The uptake of these indicators in studies of nutrition‐sensitive agricultural development projects may strengthen the evidence on how such programming can enhance women's empowerment to improve health and nutrition outcomes for themselves and their children.

AimRare genetic variants in the CUBN gene encoding the main albumin-transporter in the proximal tubule of the kidneys have previously been associated with microalbuminuria and higher urine albumin levels, also in diabetes. Sequencing studies in isolated proteinuria suggest that these variants might not affect kidney function, despite proteinuria. However, the relation of these CUBN missense variants to the estimated glomerular filtration rate (eGFR) is largely unexplored. We hereby broadly examine the associations between four CUBN missense variants and eGFRcreatinine in Europeans with Type 1 (T1D) and Type 2 Diabetes (T2D). Furthermore, we sought to deepen our understanding of these variants in a range of single- and aggregate- variant analyses of other kidney-related traits in individuals with and without diabetes mellitus.MethodsWe carried out a genetic association-based linear regression analysis between four CUBN missense variants (rs141640975, rs144360241, rs45551835, rs1801239) and eGFRcreatinine (ml/min/1.73 m2, CKD-EPIcreatinine(2012), natural log-transformed) in populations with T1D (n ~ 3,588) or T2D (n ~ 31,155) from multiple European studies and in individuals without diabetes from UK Biobank (UKBB, n ~ 370,061) with replication in deCODE (n = 127,090). Summary results of the diabetes-group were meta-analyzed using the fixed-effect inverse-variance method.ResultsAlbeit we did not observe associations between eGFRcreatinine and CUBN in the diabetes-group, we found significant positive associations between the minor alleles of all four variants and eGFRcreatinine in the UKBB individuals without diabetes with rs141640975 being the strongest (Effect=0.02, PeGFR_creatinine=2.2 × 10-9). We replicated the findings for rs141640975 in the Icelandic non-diabetes population (Effect=0.026, PeGFR_creatinine=7.7 × 10-4). For rs141640975, the eGFRcreatinine-association showed significant interaction with albuminuria levels (normo-, micro-, and macroalbuminuria; p = 0.03). An aggregated genetic risk score (GRS) was associated with higher urine albumin levels and eGFRcreatinine. The rs141640975 variant was also associated with higher levels of eGFRcreatinine-cystatin C (ml/min/1.73 m2, CKD-EPI2021, natural log-transformed) and lower circulating cystatin C levels.ConclusionsThe positive associations between the four CUBN missense variants and eGFR in a large population without diabetes suggests a pleiotropic role of CUBN as a novel eGFR-locus in addition to it being a known albuminuria-locus. Additional associations with diverse renal function measures (lower cystatin C and higher eGFRcreatinine-cystatin C levels) and a CUBN-focused GRS further suggests an important role of CUBN in the future personalization of chronic kidney disease management in people without diabetes.

Antenatal care (ANC) is an opportunity to receive interventions that can prevent low birth weight (LBW). We sought to 1) estimate LBW prevalence and burden in South Asia, 2) describe the number of ANC visits (quantity) and interventions received (quality), and 3) explore associations between ANC quantity, quality and LBW. We used Demographic and Health Survey (DHS) data from Afghanistan (2015), Bangladesh (2018), India (2016), Nepal (2016), Pakistan (2018) and Sri Lanka (2016) (n = 146,284 children

Abstract Low coverage of effective nutrition interventions in many high‐burden countries, due to service provision and demand factors, result in poor uptake of recommended practices and nutrition outcomes. We examined the factors that influence maternal nutrition and early breastfeeding practices and determined the extent that the key factors could improve these practices in two regions in Burkina Faso. We used household survey data among pregnant (n = 920) and recently delivered women (n = 1840). Multivariable regression analyses were conducted to identify the determinants of a diverse diet and iron‐folic acid (IFA) supplement consumption, weight monitoring during pregnancy and early initiation of breastfeeding (EIBF). Population attributable risk analysis was used to estimate how much the outcomes can be improved under optimal conditions of interventions that address the modifiable determinants. During pregnancy, 21% of women achieved minimum diet diversity (MDD‐W), 70% consumed 90+ IFA tablets and 65% were weighed 4+ times; EIBF was 40%. Nutrition knowledge was associated with MDD‐W (odds ratio [OR]: 3.2), 90+ IFA (OR: 1.5) and EIBF (OR: 1.9). Positive social norms and family support were associated with 90+ IFA (OR: 1.5). Early and 4+ ANC visits were associated with 90+ IFA (OR: 1.5 and 10) and 4+ weight monitoring (OR: 6.2). Nutrition counselling was associated with 90+ IFA (OR: 2.5) and EIBF (OR: 1.5). Under optimal programme conditions, 41% of women would achieve MDD‐W, 93% would consume 90+ IFA, 93% would be weighed 4+ times and 57% would practice EIBF. Strengthening the delivery and uptake of interventions targeted at these modifiable factors has the potential to improve maternal nutrition practices.

Abstract Integrating nutrition interventions into antenatal care (ANC) requires adapting global recommendations to fit existing health systems and local contexts, but the evidence is limited on the process of tailoring nutrition interventions for health programmes. We developed and integrated maternal nutrition interventions into ANC programmes in Bangladesh, Burkina Faso, Ethiopia and India by conducting studies and assessments, developing new tools and processes and field testing integrated programme models. This paper elucidates how we used information and data to contextualize a package of globally recommended maternal nutrition interventions (micronutrient supplementation, weight gain monitoring, dietary counselling and counselling on breastfeeding) and describes four country‐specific health service delivery models. We developed a Theory of Change to illustrate common barriers and strategies for strengthening nutrition interventions during ANC. We used multiple information sources including situational assessments, formative research, piloting and pretesting results, supply assessments, stakeholder meetings, household and service provider surveys and monitoring data to design models of maternal nutrition interventions. We developed detailed protocols for implementing maternal nutrition interventions; reinforced staff capacity, nutrition counselling, monitoring systems and community engagement processes; and addressed micronutrient supplement supply bottlenecks. Community‐level activities were essential for complementing facility‐based services. Routine monitoring data, rapid assessments and information from intensified supervision were important during the early stages of implementation to improve the feasibility and scalability of models. The lessons from addressing maternal nutrition in ANC may serve as a guide for tackling missed opportunities for nutrition within health services in other contexts.

Summary: Background: Schistosomiasis is an underestimated neglected tropical disease which affects over 236.6 million people worldwide. According to the CDC, the impact of this disease is second to only malaria as the most devastating parasitic infection. Affected individuals manifest chronic pathology due to egg granuloma formation, destroying the liver over time. The only FDA approved drug, praziquantel, does not protect individuals from reinfection, highlighting the need for a prophylactic vaccine. Schistosoma mansoni Cathepsin B (SmCB) is a parasitic gut peptidase necessary for helminth growth and maturation and confers protection as a vaccine target for intestinal schistosomiasis. Methods: An SmCB expressing human adenovirus serotype 5 (AdSmCB) was constructed and delivered intramuscularly to female C57BL/6 mice in a heterologous prime and boost vaccine with recombinant protein. Vaccine induced immunity was described and subsequent protection from parasite infection was assessed by analysing parasite burden and liver pathology. Findings: Substantially higher humoral and cell-mediated immune responses, consisting of IgG2c, Th1 effectors, and polyfunctional CD4+ T cells, were induced by the heterologous administration of AdSmCB when compared to the other regimens. Though immune responses favoured Th1 immunity, Th2 responses provided by SmCB protein boosts were maintained. This mixed Th1/Th2 immune response resulted in significant protection from S. mansoni infection comparable to other vaccine formulations which are in clinical trials. Schistosomiasis associated liver pathology was also prevented in a murine model. Interpretation: Our study provides missing preclinical data supporting the use of adenoviral vectoring in vaccines for S. mansoni infection. Our vaccination method significantly reduces parasite burden and its associated liver pathology - both of which are critical considerations for this helminth vaccine. Funding: This work was supported by the Canadian Institutes of Health Research, R. Howard Webster Foundation, and the Foundation of the McGill University Health Centre.

Abstract Background The COVID-19 pandemic resulted in a transformation of clinical care practices to protect both patients and providers. These changes led to a decrease in patient volume, impacting physician trainee education due to lost clinical and didactic opportunities. We measured the prevalence of trainee concern over missed educational opportunities and investigated the risk factors leading to such concerns. Methods All residents and fellows at a large academic medical center were invited to participate in a web-based survey in May of 2020. Participants responded to questions regarding demographic characteristics, specialty, primary assigned responsibility during the previous 2 weeks (clinical, education, or research), perceived concern over missed educational opportunities, and burnout. Multivariable logistic regression was used to assess the relationship between missed educational opportunities and the measured variables. Results 22% (301 of 1375) of the trainees completed the survey. 47% of the participants were concerned about missed educational opportunities. Trainees assigned to education at home had 2.85 [95%CI 1.33–6.45] greater odds of being concerned over missed educational opportunities as compared with trainees performing clinical work. Trainees performing research were not similarly affected [aOR = 0.96, 95%CI (0.47–1.93)]. Trainees in pathology or radiology had 2.51 [95%CI 1.16–5.68] greater odds of concern for missed educational opportunities as compared with medicine. Trainees with greater concern over missed opportunities were more likely to be experiencing burnout (p = 0.038). Conclusions Trainees in radiology or pathology and those assigned to education at home were more likely to be concerned about their missed educational opportunities. Residency programs should consider providing trainees with research or at home clinical opportunities as an alternative to self-study should future need for reduced clinical hours arise.

Given the lack of formalized cross-cultural mentorship guidelines within professional counseling associations and accreditation programs, the recruitment and retention of marginalizedgraduate students, may be in jeopardy. The authors explored the value of mentoring for graduate students, the exponential growth rate of diversity within graduate programs, and how the disparity of marginalized faculty members creates a need and opportunity for cross-cultural mentorship. Recommendations for the creation of holistic cross-culturalmentorship guidelines for faculty-studentdyads are provided.

BackgroundThe present study investigated the safety and efficacy of mapping and ablating isolated premature atrial contractions (PACs) in patients with a structurally normal heart, as well as whether the elimination of PACs by radiofrequency catheter ablation (RFCA) improved symptoms and the quality of life.MethodsForty-three consecutive patients with frequent, symptomatic, and drug-refractory PACs, but without atrial tachyarrhythmias (≥5 beats), were enrolled. In all patients, we performed physical, laboratory, and imaging examinations to exclude structural heart disease. The quality of life questionnaire SF-36 before and 3 months after RFCA was performed in each patient.ResultsTwenty-three men and 20 women with an average age of 52.6 ± 17.6 years were finally enrolled. The mean number of PACs was 21,685 ± 9,596 per 24 h, and the mean PACs' burden was 28.9 ± 13.7%. Short runs of tachycardia (

A patient with recent thoracic outlet decompression surgery presented with acute dyspnea and was found by point-of-care ultrasound to have diaphragm dysfunction. This case highlights an unexpected cause of respiratory complaints in the outpatient setting discovered at the bedside, utilizing point-of-care ultrasound protocol.

Background: The management of patients with atrial fibrillation and an abnormally fast ventricular response has been through the use of pharmacologic agents. In those cases where rate control cannot be achieved pharmacologically, a standard approach has been atrioventricular (AV) junctional ablation and ventricular pacemaker implantation to achieve a stable ventricular rate. Long-term ventricular pacing has been shown to result in diminished ventricular function that can lead to heart failure. Objective: To describe an experimental and clinical study demonstrating a modified form of AV junction ablation. Methods: Ablation of the slow and fast AV nodal input does not produce AV block. Ablation of the connection between the two induces AV block, leaving the AV node and His bundle intact. Results: Subsequently the escape heart rate is close to normal and responds well to exercise. Conclusion: In a clinical study with a 42 month follow-up, the modified procedure resulted in significantly reduced pacemaker dependence and mortality compared to the standard AV ablation procedure.

Abstract Designing survey questions that clearly and precisely communicate the question's intent and elicit responses based on the intended interpretation is critical but often undervalued. We used cognitive interviewing to qualitatively assess respondents' interpretation of and responses to questions pertaining to maternal and child nutrition intervention coverage. We conducted interviews to cognitively test 25 survey questions with mothers (N = 21) with children less than 1 year in Madhya Pradesh, India. Each question was followed by probes to capture information on four cognitive stages—comprehension, retrieval, judgement, and response. Data were analysed for common and unique patterns across the survey questions. We identified four types of cognitive challenges: (1) retention of multiple concepts in long questions: difficulty in comprehending and retaining questions with three or more key concepts; (2) temporal confusion: difficulty in conceptualizing recall periods such as “in the last 6 months” as compared to life stages such as pregnancy; (3) interpretation of concepts: mismatch of information being asked, meaning of certain terms and intervention scope; and (4) understanding of technical terms: difficulty in understanding commonly used technical words such as “breastfeeding” and “antenatal care” and requiring use of simple alternative language. Findings from this study will be useful for stakeholders involved in survey design and implementation, especially those conducting large‐scale household surveys to measure coverage of essential nutrition interventions.

Differentiation of pluripotent stem cells (PSCs) is a promising approach to obtaining large quantities of skeletal myogenic progenitors for disease modeling and cell-based therapy. However, generating skeletal myogenic cells with high regenerative potential is still challenging. We recently reported that skeletal myogenic progenitors generated from mouse PSC-derived teratomas possess robust regenerative potency. We have also found that teratomas derived from human PSCs contain a skeletal myogenic population. Here, we showed that these human PSC-derived skeletal myogenic progenitors had exceptional engraftability. A combination of cell surface markers, CD82, ERBB3, and NGFR enabled efficient purification of skeletal myogenic progenitors. These cells expressed PAX7 and were able to differentiate into MHC+ multinucleated myotubes. We further discovered that these cells are expandable in vitro. Upon transplantation, the expanded cells formed new dystrophin+ fibers that reconstituted almost ¾ of the total muscle volume, and repopulated the muscle stem cell pool. Our study, therefore, demonstrates the possibility of producing large quantities of engraftable skeletal myogenic cells from human PSCs.

Skeletal muscle stem cells are essential to muscle homeostasis and regeneration after injury, and have emerged as a promising cell source for treating skeletal disorders. An attractive approach to obtain these cells utilizes differentiation of pluripotent stem cells (PSCs). We recently reported that teratomas derived from mouse PSCs are a rich source of skeletal muscle stem cells. Here, we showed that teratoma formation is also capable of producing skeletal myogenic progenitors from human PSCs. Using single-cell transcriptomics, we discovered several distinct skeletal myogenic subpopulations that represent progressive developmental stages of the skeletal myogenic lineage and recapitulate human embryonic skeletal myogenesis. We further discovered that ERBB3 and CD82 are effective surface markers for prospective isolation of the skeletal myogenic lineage in human PSC-derived teratomas. Therefore, teratoma formation provides an accessible model for obtaining human skeletal myogenic progenitors from PSCs.

Abstract Limited evidence exists on the complex relationship among interventions, early initiation of breastfeeding (EIBF), prelacteal feeding and exclusive breastfeeding (EBF). We examined whether early breastfeeding practices are associated with EBF and how much improving EIBF and non‐prelacteal feeding contributes to increased prevalence of EBF. Survey data were collected in 2010 and 2014 as part of impact evaluations of Alive & Thrive (A&T) interventions to improve infant and young child feeding (IYCF) practices in Bangladesh, Vietnam and Ethiopia. Multivariable logistic regression analyses were used to examine effects of interventions and early breastfeeding practices on EBF. Structural equation modelling quantified the direct and indirect effects of interventions (via improving EIBF and non‐prelacteal feeding) on EBF. Although breastfeeding is nearly universal in all three countries (≥98%), delayed initiation of breastfeeding is prevalent (>60%) and prelacteal feeding is common. EIBF alone was not associated with EBF, whereas non‐prelacteal feeding was associated with 1.6–3.5 higher odds of EBF. Intervention exposure affected breastfeeding practices in all three countries; these impacts were amplified among those who practiced EIBF or non‐prelacteal feeding [odds ratio (OR) = 11 and 27.5 in Bangladesh and 6.5 and 11.5 in Vietnam, respectively]. The paths through EIBF and non‐prelacteal feeding explained 13%–18% of the effect of the interventions on EBF. Early breastfeeding practices influence EBF, but interventions aimed only at the initiation and early days of breastfeeding will be inadequate to promote EBF. Social and behaviour change interventions should simultaneously target EIBF, non‐prelacteal feeding and EBF to support optimal breastfeeding practices.

Abstract Most countries implement nutrition counselling interventions as part of programmes to support breastfeeding and complementary feeding. However, data to track coverage of counselling interventions are rarely available. As a result, little is known about the coverage of counselling on infant and young child feeding (IYCF). Survey‐based data collection systems generally collect data on IYCF practices but do not collect data on coverage of interventions to support IYCF, and those surveys that do collect this information do not do so consistently. We present a framework to guide the design of survey questions to measure IYCF counselling coverage. We provide examples of how large‐scale surveys for programme evaluation and national monitoring have included survey questions to address these data gaps. Our review suggests that elements relevant to designing survey questions to capture coverage of counselling interventions include timing of contact, target behaviour and message content, place of contact, type of service provider, frequency of contact and mode of intervention. Application of this framework may help strengthen harmonized measurement of IYCF counselling coverage to enable better tracking of programme investments, document progress in scaling up nutrition services and allow for cross‐country comparisons. Thus, improving measurement of counselling coverage may lead to improved reach of programmes to support optimal IYCF practices.

Facioscapulohumeral muscular dystrophy is a severe myopathy that is caused by abnormal activation of DUX4, and for which a suitable mouse model does not exist. Here, the authors generate a novel mouse model with titratable expression of DUX4, and show that it recapitulates several features of the human pathology.

Abstract Background There is limited literature examining shifts in policy environments for nutrition and infant and young child feeding (IYCF) over time, and on the potential contribution of targeted advocacy to improved policy environments in low- and middle-income countries. This study tracked changes in the policy environment over a four-year period in three countries, and examined the role of targeted nutrition and IYCF advocacy strategies by a global initiative. Methods Qualitative methods, including key informant interviews, social network mapping, document and literature review, and event tracking, were used to gather data on nutrition and IYCF policies and programs, actor networks, and perceptions and salience of nutrition as an issue in 2010 and 2014 in Bangladesh, Ethiopia, and Vietnam. Theoretical frameworks from the policy sciences were used to analyze policy change over time, and drivers of change, across countries. Results The written policy environment improved to differing extents in each country. By 2014, the discourse in all three countries mirrored international priorities of stunting reduction and exclusive breastfeeding. Yet competing nutrition priorities such as acute malnutrition, food insecurity, and nutrition transitions remained in each context. Key actor groups in each country were government, civil society, development partners and the private sector. Infant formula companies, in particular, emerged as key players against enforcement of IYCF legislation. The role of a targeted IYCF advocacy and policy support initiative was well-recognized in supporting multiple facets of the policy environment in each country, ranging from alliances to legislation and implementation support. Despite progress, however, government commitment to funding, implementation, and enforcement is still emerging in each country, thus challenging the potential impact of new and improved policies. Conclusion Targeted policy advocacy can catalyze change in national nutrition and IYCF policy environments, especially actor commitment, policy guidance, and legislation. Implementation constraints – financing, capacity and commitment of systems, and competing priorities and actors – are essential to address to sustain further progress. The lack of pressing political urgency for nutrition and IYCF, and the uncertain role of international networks in national policy spaces, has implications for the potential for change.

Abstract Background Convergence of sectoral programs is important for scaling up essential maternal and child health and nutrition interventions. In India, these interventions are implemented by two government programs – Integrated Child Development Services (ICDS) and National Rural Health Mission (NRHM). These programs are designed to work together, but there is limited understanding of the nature and extent of coordination in place and needed at the various administrative levels. Our study examined how intersectoral convergence in nutrition programming is operationalized between ICDS and NRHM from the state to village levels in Odisha, and the factors influencing convergence in policy implementation and service delivery. Methods Semi-structured interviews were conducted with state-level stakeholders (n = 12), district (n = 19) and block officials (n = 66), and frontline workers (FLWs, n = 48). Systematic coding and content analysis of transcripts were undertaken to elucidate themes and patterns related to the degree and mechanisms of convergence, types of actions/services, and facilitators and barriers. Results Close collaboration at state level was observed in developing guidelines, planning, and reviewing programs, facilitated by a shared motivation and recognized leadership for coordination. However, the health department was perceived to drive the agenda, and different priorities and little data sharing presented challenges. At the district level, there were joint planning and review meetings, trainings, and data sharing, but poor participation in the intersectoral meetings and limited supervision. While the block level is the hub for planning and supervision, cooperation is limited by the lack of guidelines for coordination, heavy workload, inadequate resources, and poor communication. Strong collaboration among FLWs was facilitated by close interpersonal communication and mutual understanding of roles and responsibilities. Conclusions Congruent or shared priorities and regularity of actions between sectors across all levels will likely improve the quality of coordination, and clear roles and leadership and accountability are imperative. As convergence is a means to achieving effective coverage and delivery of services for improved maternal and child health and nutrition, focus should be on delivering all the essential services to the mother-child dyads through mechanisms that facilitate a continuum of care approach, rather than sectorally-driven, service-specific delivery processes.

Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study ( n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend

Background: The NRG1/ErbB4 signaling mechanism has been widely studied in the central nervous system for many years. However, the role of this pathway in modulating the intrinsic cardiac nervous system is largely unknown.Objective: The present study investigated whether the NRG1/ErbB4 signaling system affects the activity of major atrial ganglionated plexi (GP) in a paroxysmal atrial fibrillation (AF) model by 6-h rapid atrial pacing (RAP).Methods: Twenty-four dogs were randomly divided into (1) a control group (saline microinjections into GP), (2) RAP group (saline microinjections into GP plus 6 h-RAP), (3) NRG1 group (microinjections of neuregulin-1 into GP plus 6 h-RAP) and (4) NRG1 + ERA group (microinjections of neuregulin-1 and ErbB4 receptor antagonist-ERA into GP plus 6 h-RAP). The effective refractory period (ERP), window of vulnerability (WOV), anterior right GP (ARGP) function and neural activity were measured. ARGP tissues were excised for histological study and western blotting.Results: When compared to the control group, 6 h-RAP produced a significant (1) decrease in ERP, an increase in ΣWOV, (2) an increase in ARGP neural activity and neural function, and (3) an increase in c-fos and nerve growth factor protein expression in the ARGP. However, microinjection of NRG1 into the ARGP prior to RAP prevented ERP shortening and AGRP activity enhancement and inhibited the expression of c-Fos and NGF proteins. Furthermore, these changes were significantly attenuated by pretreatment with an ErbB4 receptor antagonist.Conclusion: The NRG1/ErbB4 signaling pathway may exist in the GP, and activation of this pathway suppressed RAP-induced GP activation, atrial electrical remodeling and AF.

Traditional education models face great challenges from mobile devices, social networks and open courseware. Current professional knowledge and system design skills are inadequate for engineering-tracked students to thrive in a competitive job market and unpredictable professional contexts, which require them to develop unique ideas and innovations and know how to realize them. This study seeks to establish instructional arrangements in system engineering education to foster student creativity. A semester-long “embedded operating system (EOS)” course was offered as a trial system engineering course. In the paper, we explain the instructional challenges encountered and how these were addressed using the proposed Capability-Innovation-Motive (CIM) teaching model. Based on the CIM model, the EOS syllabus was redesigned to enhance student domain capabilities and build their innovative skills to help them better understand and manage abstract concepts discussed in the lectures. We then collected and analyzed student feedback by implementing Day Reconstruction Method (DRM). Analysis results show that the outcomes of both the best and worst final projects show a promising degree of creativity.

There is considerable global evidence on the effectiveness of cash transfers in improving health and nutrition outcomes; however, the evidence from South Asia, particularly India, is limited. In the context of India where more than a third of children are undernourished, and where there is considerable under-utilization of health and nutrition interventions, it is opportune to investigate the impact of cash transfer programs on the use of interventions. We study one conditional cash transfer program, Mamata scheme, implemented in the state of Odisha, in India that targeted pregnant and lactating women. Using survey data on 1161 households from three districts in the state of Odisha, we examine the effect of the scheme on eight outcomes: 1) pregnancy registration; 2) receipt of antenatal services; 3) receipt of iron and folic acid (IFA) tablets; 4) exposure to counseling during pregnancy; 5) exposure to postnatal counseling; 6) exclusive breastfeeding; 7) full immunization; and 8) household food security. We conduct regression analyses and correct for endogeneity using nearest-neighbor matching and inverse-probability weighting models. We find that the receipt of payments from the Mamata scheme is associated with a 5 percentage point (pp) increase in the likelihood of receiving antenatal services, a 10 pp increase in the likelihood of receiving IFA tablets, and a decline of 0.84 on the Household Food Insecurity Access Scale. These results provide the first quantitative estimates of effects associated with the Mamata scheme, which can inform the design of government policies related to conditional cash transfers.

Improving maternal nutrition practices during pregnancy is essential to save lives and improve health outcomes for both mothers and babies. This paper examines the maternal, household, and health service factors influencing maternal nutrition practices in the context of a large scale maternal, newborn, and child health (MNCH) program in Bangladesh. Data were from a household survey of pregnant (n = 600) and recently delivered women (n = 2,000). Multivariate linear and logistic regression analyses were used to examine the determinants of three outcomes: consumption of iron and folic acid (IFA) tablets, calcium tablets, and diverse diets. Women consumed 94 ± 68 IFA and 82 ± 66 calcium tablets (out of 180 as recommended) during pregnancy, and only half of them consumed an adequately diverse diet. Good nutrition knowledge was the key maternal factor associated with higher consumption of IFA (β = 32.5, 95% CI: 19.5, 45.6) and calcium tablets (β ~31.9, 95% CI: 20.9, 43.0) and diverse diet (OR = 1.8, 95% CI: 1.0-3.1), compared to poor knowledge. Women's self-efficacy in achieving the recommended practices and perception of enabling social norms were significantly associated with dietary diversity. At the household level, women who reported a high level of husband's support were more likely to consume IFA (β = 25.0, 95% CI: 18.0, 32.1) and calcium (β = 26.6, 95% CI: 19.4, 33.7) tablets and diverse diet (OR = 1.9, 95% CI: 1.2, 3.3), compared to those who received low support. Health service factors associated with higher intakes of IFA and calcium tablets were early and more prenatal care visits and receipt of free supplements. Combined exposure to several of these factors was attributed to the consumption of an additional 46 IFA and 53 calcium tablets and 17% higher proportions of women consuming diverse diets. Our study shows that improving knowledge, self-efficacy and perceptions of social norms among pregnant women, and increasing husbands' support, early registration in prenatal care, and provision of free supplements will largely improve maternal nutrition practices.

There is no consensus in the stem cell field as to what constitutes the mature cardiac myocyte. Thus, helping formalize a molecular signature for cardiac myocyte maturation would advance the field. In the mammalian heart, inactivation of the “fetal” TNNI gene, TNNI1 (ssTnI), together in temporal concert with its stoichiometric replacement by the adult TNNI gene product, TNNI3 (cTnI), represents a quantifiable ratiometric maturation signature. We examined the TNNI isoform transition in human induced pluripotent stem cell (iPSC) cardiac myocytes (hiPSC-CMs) and found the fetal TNNI signature, even during long-term culture. Rodent stem cell-derived and primary myocytes, however, transitioned to the adult TnI profile. Acute genetic engineering of hiPSC-CMs enabled a rapid conversion toward the mature TnI profile. While there is no single marker to denote the mature cardiac myocyte, we propose that tracking the cTnI:ssTnI protein isoform ratio provides a valuable maturation signature to quantify myocyte maturation status across laboratories.

BackgroundBotulinum toxin (BTX), temporarily suppressing cholinergic transmission (

Optimal breastfeeding (BF) practices in Ethiopia are far below the government's targets, and complementary feeding practices are poor. The Alive & Thrive initiative aimed to improve infant and young child feeding (IYCF) practices through large-scale implementation of social and behavior change communication interventions in four regions of Ethiopia. The study assessed the effects of the interventions on IYCF practices and anthropometry over time in two regions-Southern Nations, Nationalities and Peoples Region and Tigray. A pre- and post-intervention adequacy evaluation design was used; repeated cross-sectional surveys of households with children aged 0-23.9 mo (n = 1481 and n = 1494) and with children aged 24-59.9 mo (n = 1481 and n = 1475) were conducted at baseline (2010) and endline (2014), respectively. Differences in outcomes over time were estimated using regression models, accounting for clustering and covariates. Plausibility analyses included tracing recall of key messages and promoted foods and dose-response analyses. We observed improvements in most WHO-recommended IYCF indicators. Early BF initiation and exclusive BF increased by 13.7 and 9.4 percentage points (pp), respectively. Differences for timely introduction of complementary foods, minimum dietary diversity (MDD), minimum meal frequency (MMF), minimum acceptable diet (MAD), and consumption of iron-rich foods were 22.2, 3.3, 26.2, 3.5, and 2.7 pp, respectively. Timely introduction and intake of foods promoted by the interventions improved significantly, but anthropometric outcomes did not. We also observed a dose-response association between health post visits and early initiation of BF (OR: 1.8); higher numbers of home visits by community volunteers and key messages recalled were associated with 1.8-4.4 times greater odds of achieving MDD, MMF, and MAD, and higher numbers of radio spots heard were associated with 3 times greater odds of achieving MDD and MAD. The interventions were associated with plausible improvements in IYCF practices, but large gaps in improving children's diets in Ethiopia remain, particularly during complementary feeding.

Adequate utilization of services is critical to maximize the impact of counselling on infant and young child feeding (IYCF), but little is known about factors affecting utilization. Our study examined supply- and demand-side factors associated with the utilization of IYCF counselling services in Viet Nam. We used survey data from mothers with children

In the originally published version of this Article, an incorrect grant number, RO1 NS083549, was acknowledged. The correct grant number is RO1 AR055685. This error has now been corrected in both the PDF and HTML versions of the Article.

The present study investigated the following issues: (1) whether differences are evident in the eye movement measures of successful and unsuccessful problem-solvers; (2) what is the relationship between perceived difficulty and eye movement measures; and (3) whether eye movements in various AOIs differ when solving problems. Sixty-three 11th grade students solved five geometry problems about the properties of similar triangles. A digital drawing tablet and sensitive pressure pen were used to record the responses. The results indicated that unsuccessful solvers tended to have more fixation counts, run counts, and longer dwell time on the problem area, whereas successful solvers focused more on the calculation area. In addition, fixation counts, dwell time, and run counts in the diagram area were positively correlated with the perceived difficulty, suggesting that understanding similar triangles may require translation or mental rotation. We argue that three eye movement measures (i.e., fixation counts, dwell time, and run counts) are appropriate for use in examining problem solving given that they differentiate successful from unsuccessful solvers and correlate with perceived difficulty. Furthermore, the eye-tracking technique provides objective measures of students’ cognitive load for instructional designers.

It is important to cultivate dispositions of 21st-century skills (D21S: critical thinking, complex problem solving, creativity, communication, and collaboration) in project-based science, technology, engineering, and mathematics learning (STEM-PjBL). Previous research has seldom adopted the person-oriented approach to examine STEM-PjBL program effectiveness, and knowledge regarding group differences is still lacking. To fill this gap, a person-oriented analysis was used to form groupings of students based on D21S. Three latent profiles (high-, medium-, and low-D21S) of students were identified in 6 elementary schools, and the transition probabilities were estimated for 2 class types (treatment vs. comparison) across 1 semester. Most of the students (63.4%) showed stable D21S profiles over 1 semester; however, some students (17.6%) exhibited improvement, and some (18.9%) showed declination. Additionally, the STEM-PjBL programs presented positive effects on the growth of D21S. This study further found that the D21S transitional types (i.e. declined, stable, and improved) could predict students' motivation (perceived STEM domain content mastery, self-efficacy, and task value), showing that a declined D21S also decreased academic motivation. The findings suggest that students who decline in D21S should receive attention from teachers because their perceived academic performance, competence beliefs, and values in STEM also decrease simultaneously.