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Background: In the past decade, catheter ablation (CA) has become a rapidly expanding treatment option for ventricular tachycardia (VT); however it is not commonly utilised for patients with post-myocarditis VT. We aimed to systematically review up-to-date evidence regarding feasibility, effectiveness, and safety of CA, with a specific focus on long-term relapse rate and procedural complications., Methods: A structured electronic database search (PubMed, Embase, Cochrane) of the scientific literature was performed according to PRISMA guidelines for studies describing outcomes at up to 7.3 years after CA. The primary outcome measured was VT recurrence post-ablation. Procedural success was defined as freedom of ventricular arrhythmias (at the end of follow-up after an ablation procedure). The secondary outcome was significant procedural complications which included procedural death, stroke, cardiac tamponade, acute myocardial infarction, major vascular complications, and major bleeding, assessed on a study-by-study basis., Results: A total of 186 patients were included in analysis with most patients (88%) being male. Over the follow-up period, there was a 18% relapse rate ( n  = 34) (confidence interval (CI); 0.12-0.24, I 2 ≈0, p  = 0.77) with the majority of patients remaining VT free for the duration of follow-up. The overall procedural complication rate was 3.0% ( n  = 7) (CI; 0.01-0.07, I 2 ≈0, p  = 0.44), and of note, there were no peri-procedural deaths or heart transplant surgeries reported. However, a single study reported a mortality of 10% ( n  = 2) during the follow-up period., Conclusions: CA is an effective and durable long-term therapeutic strategy for post-myocarditis VT patients with limited relapse rate and very low complication rates based on these non-randomised data. Larger randomised-controlled trials with standardised treatment and long follow-up are required to compare CA versus conventional treatment in the post-acute myocardial phase., Supplementary Information: The online version contains supplementary material available at 10.1007/s42399-022-01137-w., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

The National Health and Nutrition Examination Survey (NHANES) is a unique source of national data on the health and nutritional status of the US population, collecting data through interviews, standard exams, and biospecimen collection. Because of the COVID-19 pandemic, NHANES data collection was suspended, with more than a year gap in data collection. NHANES resumed operations in 2021 with the NHANES 2021-2022 survey, which will monitor the health and nutritional status of the nation while adding to the knowledge of COVID-19 in the US population. This article describes the reshaping of the NHANES program and, specifically, the planning of NHANES 2021-2022 for data collection during the COVID-19 pandemic. Details are provided on how NHANES transformed its participant recruitment and data collection plans at home and at the mobile examination center to safely collect data in a COVID-19 environment. The potential implications for data users are also discussed. ( Am J Public Health . 2021;111(12):2149-2156. https://doi.org/10.2105/AJPH.2021.306517).

Better adherence to dietary guidelines during pregnancy is supposed to result in healthier perinatal outcomes. We aim to characterize the diets of pregnant women by hypothesis-driven and exploratory approaches and describe potential social determinants. Analyses included 12 048 mothers from the French nationwide ELFE birth cohort. Dietary intake over the last three months of the pregnancy was assessed by a food frequency questionnaire. Two hypothesis-driven scores (the Diet Quality score, based on benchmarks derived from the National Health and Nutrition Program Guidelines, and the PANDiet score, based on nutrient intake) were calculated. Exploratory dietary patterns were also identified by principal component analysis. Multiple linear regressions were used to assess associations of maternal social characteristics with dietary patterns, accounting for the possible effect modification by their migration status. Five dietary patterns were identified: the Western, Balanced, Bread and toppings, Processed products, and Milk and breakfast cereals. Younger maternal age, single motherhood, unemployment and the presence of older children in the household were related to a suboptimal diet during pregnancy. The less acculturated the women were, the healthier and less processed their diets were, independent of their socio-economic position. Several social determinants of the quality of women's diets were however moderated by their migration status. These findings shed light on the relations between indicators of social vulnerability, such as single motherhood and unemployment, and poorer diet quality. Given the reduced diet quality that accompanies the acculturation process, it is of paramount importance to identify the specific factors or obstacles that affect migrant women in maintaining their diet quality advantage over the majority population., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

In this report, we describe the case of a 5-year-old male with SARS-CoV-2 associated MIS-C with progressive respiratory failure and vasoplegic shock requiring extracorporeal support. At presentation, reverse transcription-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 was negative, however, SARS-CoV2 antibody testing was positive. Multiple inflammatory markers and cardiac biomarkers were elevated. Echocardiogram demonstrated mildly depressed left ventricular function and no coronary anomalies noted. The patient required mechanical ventilation, vasopressors, and eventually extracorporeal membrane oxygenation (ECMO) for profound circulatory shock and progressive respiratory failure. During his clinical course, recovery of cardiac function was demonstrated however, a middle cerebral artery infarct and left frontal subarachnoid hemorrhage was suffered which ultimately the patient succumbed to. To the best of our knowledge, this is the youngest previously healthy child who had multi-system hyperinflammatory syndrome requiring ECMO support and the first case of SARS-CoV-2 related pediatric stroke. Clinical Trial Registration: None.

Background: Tezacaftor-ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8-24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor-ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor-ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation., Methods: Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor-ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor-ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov (NCT02565914)., Findings: Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor-ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor-ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor-ivacaftor-treated F/F participants versus untreated matched historical controls., Interpretation: Tezacaftor-ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor-ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor-ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes., Funding: Vertex Pharmaceuticals Incorporated., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients ≥12 years of age with cystic fibrosis and at least one F508del-CFTR (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. Objectives: To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with F508del -minimal function or F508del - F508del genotypes. Methods: In this 24-week open-label phase 3 study, children ( N  = 66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 h) whereas children weighing ⩾30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h). Measurements and Main Results: The primary endpoint was safety and tolerability. The safety and pharmacokinetic profiles of ELX/TEZ/IVA were generally consistent with those observed in older patients. The most commonly reported adverse events included cough, headache, and pyrexia; in most of the children who had adverse events, these were mild or moderate in severity. Through Week 24, ELX/TEZ/IVA treatment improved the percentage of predicted FEV 1 (10.2 percentage points; 95% confidence interval [CI], 7.9 to 12.6), Cystic Fibrosis Questionnaire-Revised respiratory domain score (7.0 points; 95% CI, 4.7 to 9.2), lung clearance index 2.5 (-1.71 units; 95% CI, -2.11 to -1.30), and sweat chloride (-60.9 mmol/L; 95% CI, -63.7 to -58.2); body mass index-for-age z -score increased over the 24-week treatment period when compared with the pretreatment baseline. Conclusions: Our results show ELX/TEZ/IVA is safe and efficacious in children 6 through 11 years of age with at least one F508del-CFTR allele, supporting its use in this patient population. Clinical trial registered with www.clinicaltrials.gov (NCT03691779).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

Background: We evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping., Methods: Persistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model., Results: 46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11-14) vs 12 (10-14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p < 0.001). There was a significant shortening of CL in the adenosine maps compared to baseline which was more marked in the right atrium than left atrium (176.7 ± 34.7 vs 149.9 ± 27.7 ms; p < 0.001 and 165.6 ± 31.7 vs 148.3 ± 28.4 ms; p = 0.003)., Conclusion: Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov: NCT03394404., Competing Interests: Ross Hunter has received research grants from Medtronic, educational grants from Biosense Webster, and speaker fees from Medtronic and Biosense Webster. Pier Lambiase receives research grants from Medtronic, Abbott and Boston Scientific. This work is supported by UCLH Biomedicine NIHR and Barts BRC. Ross Hunter, Richard Schilling, and Shohreh Honarbakhsh were inventors of the STAR mapping system and are shareholders in Rhythm AI Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors https://journals.plos.org/plosone/s/competing-interests).

Background: Tezacaftor (TEZ)/ivacaftor (IVA) is an approved CFTR modulator shown to be efficacious and generally safe and well tolerated in people ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous for the F508del-CFTR mutation and a residual function mutation. Although previous studies with IVA alone showed clinical benefits in people with CFTR gating mutations, TEZ/IVA has not yet been evaluated in a Phase 3 study of participants heterozygous for F508del-CFTR and a gating mutation (F/gating genotypes). Here, we present results from a randomized, double-blind, IVA-controlled, parallel-group, Phase 3 study assessing the efficacy, safety, and pharmacokinetics (PK) of TEZ/IVA in participants ≥12 years of age with F/gating genotypes., Methods: Enrolled participants entered a 4-week IVA run-in period to create a stable IVA baseline. Participants were then randomized to receive IVA or TEZ/IVA for 8 weeks in an active comparator treatment period (ACTP). The primary endpoint was absolute change in percent predicted forced expiratory volume in 1 second (ppFEV 1 ). Key secondary endpoints were relative change in ppFEV 1 and absolute change in CF Questionnaire-Revised respiratory domain score. Secondary endpoints included absolute change in sweat chloride (SwCl) concentration, PK parameters, and safety. All endpoints except PK parameters and safety were assessed from baseline through Week 8., Results: Sixty-nine participants (92.0%) in the IVA group and 75 participants (98.7%) in the TEZ/IVA group completed treatment. No improvements were seen in efficacy endpoints from baseline at the end of the IVA run-in period through the end of the ACTP in the IVA group. No significant differences in ppFEV 1 or any key secondary endpoint were observed between the IVA and TEZ/IVA groups. SwCl concentrations decreased more in the TEZ/IVA versus IVA group during the ACTP. The safety profile and PK parameters of TEZ/IVA were consistent with those of previous studies in participants ≥12 years of age with CF., Conclusions: This Phase 3 study showed that the dual-combination regimen of TEZ/IVA demonstrated clinical efficacy but did not have significantly greater clinical efficacy than IVA alone in participants ≥12 years of age with F/gating genotypes. However, as reported in other studies, TEZ/IVA was generally safe and well tolerated (NCT02412111)., Competing Interests: Declaration of Competing Interest All authors received nonfinancial support (assistance with manuscript preparation) from ArticulateScience LLC, which received funding from Vertex Pharmaceuticals Incorporated. Additional disclosures are as follows: CAO, DC, and NA are employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in that company. EAD: grants from Vertex Pharmaceuticals Incorporated during the conduct of the study. EFM: grants and personal fees from Vertex Pharmaceuticals Incorporated during the conduct of the study; personal fees from Proteostasis Therapeutics Incorporated, other from A. Menarini, and grants from Gilead outside the submitted work. ET: grant from Vertex Pharmaceuticals Incorporated (paid to institution for conduct of clinical trials) during the conduct of the study; grants from Bayer, Boehringer Ingelheim, Celtaxsys Incorporated, Vertex Pharmaceuticals Incorporated, Corbus, and Aridigm Corporation outside the submitted work; personal fees from Proteostasis Therapeutics Incorporated (scientific advisory board), Horizon (advisory board), and Vertex Pharmaceuticals Incorporated (consulting related to scientific advisory board; honoraria for speaking) outside the submitted work. MH is an employee of Vertex Pharmaceuticals (Europe) Limited and may own stock or stock options in that company. SS: grants from Galapagos, Proteostasis Therapeutics Incorporated, Celtaxsys Incorporated, Flatley, and Vertex Pharmaceuticals Incorporated outside the submitted work; personal fees from Proteostasis Therapeutics Incorporated, Novartis Pharma GmbH, Vertex Pharmaceuticals Incorporated, Teva GmbH, and Chiesi GmbH outside the submitted work. TLB: personal fees from Respirtech Technologies outside the submitted work., (Copyright © 2020. Published by Elsevier B.V.)

Background: Increased rates of respiratory adverse events have been observed in people ≥12 years of age with cystic fibrosis homozygous for the Phe508del-CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV 1 ) of <40%. We evaluated the safety, tolerability, and efficacy of tezacaftor/ivacaftor in people with cystic fibrosis homozygous for Phe508del-CFTR who discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms., Methods: Participants ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV 1 of ≥25% and ≤90% were randomized 1:1 and treated with tezacaftor/ivacaftor or placebo for 56 days., Results: Of 97 participants, 94 (96.9%) completed the study. The primary endpoint was incidence of predefined respiratory adverse events of special interest (chest discomfort, dyspnea, respiration abnormal, asthma, bronchial hyperreactivity, bronchospasm, and wheezing): tezacaftor/ivacaftor, 14.0%; placebo, 21.3%. The adverse events were mild or moderate in severity. None were serious or led to treatment interruption or discontinuation. Overall, the discontinuation rate was similar between groups. The mean (SD) ppFEV 1 at baseline was 44.6% (16.1%) with tezacaftor/ivacaftor and 48.0% (18.1%) with placebo. The posterior mean difference in absolute change in ppFEV 1 from baseline to the average value of days 28 and 56 was 2.7 percentage points with tezacaftor/ivacaftor vs placebo., Conclusions: Tezacaftor/ivacaftor was generally safe, well tolerated, and efficacious in people ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV 1 of ≥25% and ≤90% who previously discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms., Competing Interests: Declaration of Competing Interests All authors received nonfinancial support (assistance with manuscript preparation) from ArticulateScience LLC, which received funding from Vertex. Additional disclosures are as follows. BGB, MED, and NA are employees of Vertex and may own stock or stock options in Vertex. PKA, TJF and XY are former employees of Vertex and may own stock or stock options in Vertex. CS received a grant from Vertex and personal fees from Vertex, PTI, Chiesi, and Teva outside the submitted work. RF received an honorarium from Vertex during the conduct of the study. SMR received grants, personal fees, and nonfinancial support from Vertex during the conduct of the study; grants from Bayer, Forest Research Institute, AstraZeneca, Nivalis, Novartis, Galapagos/AbbVie, Proteostasis, Eloxx, Celtaxsys, PTC, and Vertex; personal fees from Bayer, Celtaxsys, Novartis, and Vertex; and nonfinancial support from Vertex outside the submitted work. SS received personal fees from Proteostasis, Novartis and Vertex outside the submitted work; has served as an investigator in clinical trials for Galapagos, Proteostasis, Celtaxsys, Flatley, Novartis, and Vertex; and has consulted for Proteostasis and Vertex. RCK and RE have no additional disclosures., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The CFTR modulator tezacaftor/ivacaftor was efficacious and generally safe and well tolerated in Phase 3 studies in participants ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous with a residual function-CFTR mutation (F/F or F/RF respectively). We evaluated tezacaftor/ivacaftor's efficacy and safety over 8 weeks in participants 6 through 11 years of age with these mutations., Methods: Participants were randomized 4:1 to tezacaftor/ivacaftor or a blinding group (placebo for F/F, ivacaftor for F/RF). The primary endpoint was within-group change from baseline in the lung clearance index 2·5 (LCI 2·5 ) through Week 8. Secondary endpoints were change from baseline in sweat chloride (SwCl), cystic fibrosis questionnaire-revised (CFQ-R) respiratory domain score, and safety., Results: Sixty-seven participants received at least one study drug dose. Of those, 54 received tezacaftor/ivacaftor (F/F, 42; F/RF, 12), 10 placebo, and 3 ivacaftor; 66 completed the study. The within-group change in LCI 2·5 was significantly reduced (improved) by -0·51 (95% CI: -0·74, -0·29). SwCl concentration decreased (improved) by -12·3 mmol/L and CFQ-R respiratory domain score increased (improved, nonsignificantly) by 2·3 points. There were no serious adverse events (AEs) or AEs leading to tezacaftor/ivacaftor discontinuation or interruption. The most common AEs (≥10%) in participants receiving tezacaftor/ivacaftor were cough, headache, and productive cough., Conclusions: Tezacaftor/ivacaftor improved lung function (assessed using LCI) and CFTR function (measured by SwCl concentration) in participants 6 through 11 years of age with F/F or F/RF genotypes. Tezacaftor/ivacaftor was safe and well tolerated; no new safety concerns were identified., Competing Interests: Declaration of Competing Interest All authors received nonfinancial support (assistance with manuscript preparation) from ArticulateScience LLC, which received funding from Vertex Pharmaceuticals Incorporated. Additional disclosures are as follows: CAO, DC, EH, NA, PP, and RSH are employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in Vertex Pharmaceuticals Incorporated. CSa: LCI over reading fees with Vertex Pharmaceuticals Incorporated during the conduct of the study. CW: Income on a per-patient basis derived from pharmaceutical studies (Vertex Pharmaceuticals Incorporated and Boehringer-Ingelheim); research grant from Novo Nordisk Pharmaceuticals for the P/L-CF-IDEA study; Vertex Pharmaceuticals P/L honorarium to attend the CF International Advisory Board Meeting in February 2014; Vertex Pharmaceuticals P/L honorarium to attend CF Medical Advisory Board Meeting in Adelaide in April 2014; Novartis Pharmaceuticals P/L honorarium to present a symposium at the National Pediatric Congress in Lebanon in May 2014; Vertex Pharmaceuticals P/L return travel and honorarium for lecture & discussions at the European CF Conference in Gothenburg in June 2014; DKBmed, LLC honorarium to present symposium at the North American CF Conference Georgia in October 2014; Vertex Pharmaceuticals P/L honorarium to present as speaker in an educational meeting series in Brisbane and Sydney in April 2015; Vertex Pharmaceuticals P/L honorarium to attend the Vertex Steering Committee Meetings on the VX15-770-123 study in 2014; Vertex Pharmaceuticals P/L honorarium for Vertex Medical Advisory Board-Innovative endpoints in CF in August 2015; University of Miami honorarium for meeting attendance in 2015; Thorax honorarium for associate editor duties in Q3/Q4 2015; BMJ honorarium for work as a reviewer; Vertex Pharmaceuticals 2015 Chicago return flight and accommodation for work as investigator in lumacaftor study; Vertex Pharmaceuticals 2015-2017 honorarium for being a speaker at Vertex-sponsored educational meeting series in Australia; Vertex Pharmaceuticals 2016 Phoenix return flight and accommodation as investigator in the Next Gen study; Vertex Pharmaceuticals December 2016 honoraria for work as a speaker at a Vertex-sponsored educational meeting in Liverpool, UK; DKBmed eCF review issue honoraria in January 2017; Vertex Pharmaceuticals March 2017 honoraria for being a speaker at TSANZ meeting; Vertex Pharmaceuticals Incorporated 2014-2018 honorarium for acting as a consultant on the Vertex Orkambi 6-11 HTA Advisory Board, the Global Pediatric Advisory Committee, the Global Medical Advisory Board, and the VIA Grants Committee; Gilead Sciences Ltd. honorarium for meeting attendance on CF imaging; honorarium for In Vivo Academy Limited for webcast meeting attendance at ECFC 2018; Vertex Pharmaceuticals P/L honorarium to present as a speaker in an educational meeting at ECFC in Belgrade 2018; Vertex Pharmaceuticals Incorporated honorarium to attend the Next Gen Early Lifecycle Management Plan in London in 2018; Vertex Pharmaceuticals P/L to act as consultant and to render such services in the form of documents, advice, meetings, and conferences from October 2018 to present; Vertex Pharmaceuticals (Australia) P/L to attend as a steering committee member at the Medical Symposium Event (SHIFT 2019) in Perth in 2019; Vertex Pharmaceuticals P/L to attend the EU Real World Evidence steering committee in Amsterdam in 2019; Current board positions: International Advisory Board, Vertex Pharmaceuticals P/L; Associate Editor, Thorax; Associate Editor, Respirology. ISG: Support for scientific project and PI of different clinical trials with Vertex Pharmaceuticals Incorporated during the conduct of this study. JCD: advisory board and clinical trial lead with Algipharma AS, UK lead investigator and advisory board with Bayer AG, advisory board with Boehringer Ingelheim Pharma GmbH & Co. KG, advisory board and clinical trial leadership with Galapagos NV, advisory and trial design assistance with ImevaX GmbH, advisory board with Nivalis Therapeutics Inc, advisory board and trial design advice with ProQR Therapeutics III B.V., advisory and clinical trial leadership with Proteostasis Therapeutics Inc, advisory with Raptor Pharmaceuticals Inc, advisory board and National Co-ord/Global Co-I with Vertex Pharmaceuticals (Europe) Limited, advisory board with Enterprise, Novartis, Pulmocide, and Flatley, grant from CF Trust, and educational activities with Teva outside the submitted work. CSh and LN had nothing further to disclose., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Many endocrinopathies have been increasingly affecting females of reproductive age. Polycystic ovary syndrome (PCOS) and hypothyroidism are some of the most common endocrinopathies seen in females. The aim of this study is to find a relationship between the incidence of thyroiditis in polycystic ovarian syndrome patients. Literature review search was conducted via a series of systematic searches using multiple databases which lead to cross-referencing of articles within assigned criteria. Our study resulted in a review of 42 articles pertaining to our study. In this literature review article, factors were identified associating PCOS with thyroiditis. A viable relationship was found between the incidence of PCOS and thyroiditis. The combination of factors seen in this study proposes that clinicians may need to focus on certain markers regarding the screening of the incidence of thyroiditis. We also recommend future cohort studies to be conducted to further confirm the associations identified in this article., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Singh et al.)

The American Academy of Pediatrics recommends that children and adolescents consume breakfast for healthier body weights, improved nutrition, better memory, better test scores, and better attention spans (1). This report describes breakfast consumption among children and adolescents by sex, age, race and Hispanic origin, and family income level. Foods and beverages frequently consumed for breakfast, as well as trends in breakfast consumption over the last decade, are also reported., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Beverages play a substantial role in meeting total water intake needs and are a major contributor to overall nutrient and caloric intake for the U.S. population (1,2). The 2015-2020 Dietary Guidelines for Americans recommend that water, fat-free and low-fat milk, and 100% juice be the primary beverages consumed (2). This report provides estimates of the contribution of beverage types to total nonalcoholic beverage consumption, by grams, for U.S. adults., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Fast food has been associated with higher caloric intake and poorer diet quality in children and adolescents (1). In 2011-2012, children and adolescents aged 2-19 years consumed on average 12.4% of their daily calories from fast food on a given day (2). This report presents 2015-2018 estimates of the percentage of calories consumed from fast food on a given day among U.S. children and adolescents by demographic characteristics and trends since 2003., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

Background: Tuberculosis of the myocardium is an extremely rare entity with few published case reports. Diagnosis is often delayed, and outcomes are unfavorable: particularly when cardiac involvement has been the presenting entity., Methods: Four patients, aged 24-51 years, presented with life-threatening ventricular arrhythmia (VA). None had a previous history of tuberculosis or any structural heart disease. Electrocardiogram during sinus rhythm and Echocardiography did not show any gross abnormality. All patients underwent contrast-enhanced computer tomography of thorax and cardiac magnetic resonance imaging. Attempts to obtain tissue (cardiac or associated mediastinal lymph nodes) were associated with increased risk to the patients thus indirect evidence of Mantoux skin test and interferon gamma release assay results were used to aid diagnosis., Results: Based on clinicoradiological findings, patients were put on antitubercular therapy (ATT). Supportive therapy included antiarrhythmic drugs (all patients), catheter ablation (two patients), and implantable cardioverter defibrillator (one patient). Arrhythmia suppression was achieved in all patients predischarge. On a follow-up of 2-24 months, none of the patients has had any recurrence of arrhythmia. ATT and antiarrhythmic drug therapy have been stopped in two patients who have completed the 6 months of ATT. Their radiological lesions showed resolution., Conclusions: Myocardial tuberculosis presenting as life-threatening VA in a rare but definite clinical entity. A high index of suspicion and cardiac imaging can lead to early diagnosis and appropriate treatment that ensures survival in all patients., (© 2020 Wiley Periodicals, Inc.)

The first 2 y of life are characterized by several transitions that can affect growth, development, and eating patterns long term. These include a shift from a primarily milk-based eating pattern to introduction of complementary foods at ∼4-6 mo of age, and passage to family-meal patterns in toddler years. Recognizing the importance of this critical period, the Dietary Guidelines for Americans from 2020 onwards will include guidance for children aged birth to 24 mo (B-24). Few large-scale surveys provide comprehensive, nationally representative, quantitative, recent data on infant and toddler nutrition in the United States. The continuous NHANES has collected data relevant to this initiative since 1999 using standardized interview and examination protocols. These include data on infant feeding practices, dietary intakes (foods, beverages, and supplements), anthropometry, and blood-based nutritional status on nationally representative samples of infants and toddlers. NHANES data can be used to describe large group-level consumption patterns, as well as trends over time for B-24 children overall, and by demographic groups (e.g., race-ethnic and income groups). In addition, NHANES data can be analyzed to examine adherence to nutrition-related recommendations, such as those from the American Academy of Pediatrics (AAP), and to track Healthy People 2020 objectives. This paper provides an update on NHANES nutrition monitoring in B-24 children since our previous publication (which provided details through NHANES 2009-2010) and describes data collection since 2010 and plans for upcoming cycles. It also describes key NHANES-based findings published in the last 5 y on infant feeding practices, dietary intakes and supplement use, and nutritional status of US children aged <2 y. Findings related to existing recommendations, such as from the AAP, are presented when available. This information can inform researchers and policymakers on the state of nutrition in the US B-24 population and its subgroups of interest., (Published by Oxford University Press on behalf of the American Society for Nutrition 2019.)

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators correct the basic defect caused by CFTR mutations. Improvements in health outcomes have been achieved with the combination of a CFTR corrector and potentiator in people with cystic fibrosis homozygous for the F508del mutation. The addition of elexacaftor (VX-445), a next-generation CFTR corrector, to tezacaftor plus ivacaftor further improved F508del-CFTR function and clinical outcomes in a phase 2 study in people with cystic fibrosis homozygous for the F508del mutation., Methods: This phase 3, multicentre, randomised, double-blind, active-controlled trial of elexacaftor in combination with tezacaftor plus ivacaftor was done at 44 sites in four countries. Eligible participants were those with cystic fibrosis homozygous for the F508del mutation, aged 12 years or older with stable disease, and with a percentage predicted forced expiratory volume in 1 s (ppFEV 1 ) of 40-90%, inclusive. After a 4-week tezacaftor plus ivacaftor run-in period, participants were randomly assigned (1:1) to 4 weeks of elexacaftor 200 mg orally once daily plus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h versus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h alone. The primary outcome was the absolute change from baseline (measured at the end of the tezacaftor plus ivacaftor run-in) in ppFEV 1 at week 4. Key secondary outcomes were absolute change in sweat chloride and Cystic Fibrosis Questionnaire-Revised respiratory domain (CFQ-R RD) score. This study is registered with ClinicalTrials.gov, NCT03525548., Findings: Between Aug 3 and Dec 28, 2018, 113 participants were enrolled. Following the run-in, 107 participants were randomly assigned (55 in the elexacaftor plus tezacaftor plus ivacaftor group and 52 in the tezacaftor plus ivacaftor group) and completed the 4-week treatment period. The elexacaftor plus tezacaftor plus ivacaftor group had improvements in the primary outcome of ppFEV 1 (least squares mean [LSM] treatment difference of 10·0 percentage points [95% CI 7·4 to 12·6], p<0·0001) and the key secondary outcomes of sweat chloride concentration (LSM treatment difference -45·1 mmol/L [95% CI -50·1 to -40·1], p<0·0001), and CFQ-R RD score (LSM treatment difference 17·4 points [95% CI 11·8 to 23·0], p<0·0001) compared with the tezacaftor plus ivacaftor group. The triple combination regimen was well tolerated, with no discontinuations. Most adverse events were mild or moderate; serious adverse events occurred in two (4%) participants receiving elexacaftor plus tezacaftor plus ivacaftor and in one (2%) receiving tezacaftor plus ivacaftor., Interpretation: Elexacaftor plus tezacaftor plus ivacaftor provided clinically robust benefit compared with tezacaftor plus ivacaftor alone, with a favourable safety profile, and shows the potential to lead to transformative improvements in the lives of people with cystic fibrosis who are homozygous for the F508del mutation., Funding: Vertex Pharmaceuticals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: To determine if children with congenital heart disease (CHD) have lower newborn T-cell receptor excision circles (TREC) levels than the general population and to evaluate if low TREC levels in newborns with CHD are associated with clinical complications such as hospitalization for infection., Study Design: The Connecticut Newborn Screening Program reported TREC levels for newborns with CHD delivered between October 2011 and September 2016 at 2 major Connecticut children's hospitals. TREC levels for children with CHD were compared with the general population. TREC levels and outcome measures, including hospitalization for infection, were compared., Results: We enrolled 575 participants with CHD in the study. The median TREC level for newborns with CHD was lower than the general population (180.1 copies/μL vs 312.5 copies/μL; P < .01). patients with CHD requiring hospitalization for infection had lower median TREC levels than their counterparts (143.0 copies/μL vs 186.7 copies/μL; P < .01). The combination of prematurity and low TREC level had a strong relationship to hospitalization for infection (area under the receiver operative characteristic curve of 0.89). There was no association between TREC level and CHD severity., Conclusions: Newborns with CHD demonstrated lower TREC levels than the general population. Low TREC levels were associated with hospitalization for infection in preterm children with CHD. Study limitations include that this was a retrospective chart review. These findings may help to identify newborns with CHD at highest risk for infection, allowing for potential opportunities for intervention., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Tezacaftor/ivacaftor is a new treatment option in many regions for patients aged ≥12 years who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function (F/RF) mutation. This Phase 3, 2-part, open-label study evaluated the pharmacokinetics (PK), safety, tolerability, and efficacy of tezacaftor/ivacaftor in children aged 6 through 11 years with these mutations., Methods: Part A informed weight-based tezacaftor/ivacaftor dosages for part B. The primary objective of part B was to evaluate the safety and tolerability of tezacaftor/ivacaftor through 24 weeks; the secondary objective was to evaluate efficacy based on changes from baseline in percentage predicted forced expiratory volume in 1 s (ppFEV 1 ), growth parameters, sweat chloride, and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score., Results: After PK analysis in part A, 70 children received ≥1 dose of tezacaftor/ivacaftor in part B; 67 children completed treatment. Exposures in children aged 6 through 11 years were within the target range for those observed in patients aged ≥12 years. The safety profile of tezacaftor/ivacaftor was generally similar to prior studies in patients aged ≥12 years. One child discontinued treatment for a serious adverse event of constipation. Tezacaftor/ivacaftor treatment improved sweat chloride levels and CFQ-R respiratory domain scores, mean ppFEV 1 remained stable in the normal range, and growth parameters remained stable over 24 weeks., Conclusions: Tezacaftor/ivacaftor was generally safe and well tolerated, and improved CFTR function in children aged 6 through 11 years with CF with F/F and F/RF genotypes, supporting tezacaftor/ivacaftor use in this age group. NCT02953314., (Copyright © 2019. Published by Elsevier B.V.)

Non-insulin-dependent diabetes or type II diabetes is prevalent around the world. A high-fat diet and chronic inactivity are often responsible for this chronic ailment. However, it is suspected that a high level of stress can also exacerbate diabetes. High anxiety can result in the release of sympathetic hormones that can elevate both cortisol and glucose levels, decrease insulin release, or affect the sensitivity and resistant of the insulin hormone. We have analyzed three research articles to see how stress and anxiety can affect non-insulin-dependent diabetes. In the first article, we selected participants with type II diabetes and injected them with saline or norepinephrine. The results indicated that participants with norepinephrine had experienced a decrease in glucose disposal and reduction in insulin secretion rate. Our second article utilizes African-American adults with type II diabetes. We provide them with a survey to determine how stress, anxiety, and depression can affect adherence to lifestyle modifications such as exercise and eating a proper diet. We find that subjects with higher stress levels tend to have lower compliance with their lifestyle regimes. Our third article focuses on female participants and divides them into two categories which are high chronic stress (HCS) and low chronic stress (LCS). We use an MRI to observe their brain activity while they stare at a picture of high-caloric type food. Our results indicate that there are different responses in various brain structure activities between subjects with HCS and LCS group. With these analyses, it can improve on the way healthcare providers can consult with their patients who have exacerbated type II diabetes despite proper medication and lifestyle modification., Competing Interests: The authors have declared that no competing interests exist.

Total grains intake comes from whole grains and refined grains. Whole grains contain the entire grain kernel (bran, germ, and endosperm) (1). A higher intake of whole grains is linked with a lower risk of cardiovascular disease, cancer, and mortality (2). The "2015-2020 Dietary Guidelines for Americans" recommend that at least one-half of total grains intake be from whole grains (3). This report provides estimates of the percentage of total grains intake consumed from whole grains sources, for adults aged 20 and over who reported consumption of grains (98.6%) on a given day during 2013-2016., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Background: Limited nationally representative data are available on dietary supplement (DS) use and resulting nutrient exposures among infants and toddlers., Objective: This study evaluated DS use among US infants and toddlers to characterize DS use, estimate nutrient intake from DSs, and assess trends in DS use over time., Methods: Using nationally representative data from NHANES (2007-2014) and trends over time (1999-2014), we estimated prevalence of DS use and types of products used for US infants and toddlers aged <2 y (n = 2823). We estimated median daily intakes of vitamins and minerals consumed via DSs for all participants aged <2 y, by age groups (0-11.9 mo and 12.0-23.9 mo), and by feeding practices for infants 0-5.9 mo., Results: Overall, 18.2% (95% CI: 16.2%, 20.3%) of infants and toddlers used ≥1 DS in the past 30 d. Use was lower among infants (0-5.9 mo: 14.6%; 95% CI: 11.5%, 18.1%; 6-11.9 mo: 11.6%; 95% CI: 8.8%, 15.0%) than among toddlers (12-23.9 mo: 23.3%; 95% CI: 20.4%, 26.3%). The most commonly reported DSs were vitamin D and multivitamin infant drops for those <12 mo, and chewable multivitamin products for toddlers (12-23.9 mo). The nutrients most frequently consumed from DSs were vitamins D, A, C, and E for those <2 y; for infants <6 mo, a higher percentage of those fed breast milk than those fed formula consumed these nutrients via DSs. DS use remained steady for infants (6-11.9 mo) and toddlers from 1999-2002 to 2011-2014, but increased from 7% to 20% for infants aged 0-5.9 mo., Conclusions: One in 5 infants and toddlers aged <2 y use ≥1 DS. Future studies should examine total nutrient intake from foods, beverages, and DSs to evaluate nutrient adequacy overall and by nutrient source., (Published by Oxford University Press on behalf of the American Society for Nutrition 2019.)

Fast food is a part of the American diet and has been associated with high caloric intake (1), and poor diet quality (2). Time, financial resources, price, and availability influence fast food consumption (3). This report presents data on the percentage of adults who consumed fast food on a given day in the United States during 2013-2016., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

The 2015-2020 Dietary Guidelines for Americans (1) recommend consuming two servings of seafood, including fish and shellfish, per week. Consuming approximately 8 ounces of a variety of seafood weekly is associated with reduced cardiac deaths (2). This report describes the percentage of U.S. adults and youth who reported consuming seafood at least two times per week by sex, age, and race and Hispanic origin during 2013-2016. Trends in the percentage of adults and youth who consumed seafood at least twice weekly, from 2005-2006 through 2015-2016, are also presented., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Purpose of Review: Pre-participation athlete screening has led to the referral of asymptomatic athletes with a prolonged QT interval warranting their evaluation for long QT syndrome (LQTS). Establishing a diagnosis of LQTS can be difficult, particularly in asymptomatic athletes presenting with a prolonged QTc < 500 ms. This review examines the evaluatory pathway to ascertain the common pitfalls leading to mis- or overdiagnosis. We discuss the advanced ECG-based tools and consider their application in the diagnostic process., Recent Findings: Critical analysis of the ECG, symptom, and pedigree analysis has established value but relies on experienced interpretation. Protocolisation of the former has effectively reduced error. Exercise recovery ECG testing has demonstrated diagnostic value and provocation testing, reliant on QT hysteresis in LQTS, have shown reasonable sensitivity. Although it is becoming more established in experienced centres, its diagnostic value relies on effective risk stratification and subject selection. LQTS is a rare condition and the precision of any available test is greatly diluted if pre-test probability is low. Clinical and familial evaluation and exercise ECG testing are the foundation of the evaluatory process following referral. Adjunctive tests may have high sensitivity for LQTS but rely on high pre-test probability. Several pitfalls have been identified that can lead to misdiagnosis and thus informed evaluation at an experienced specialist centre is appropriate.

Objective: This review summarizes the current and previous data on dietary supplement (DS) use collected from participants in the National Health and Nutrition Examination Survey (NHANES), describes the NHANES dietary supplement database used to compute nutrient intakes from DSs, discussed recent developments and future direction, and describes many examples to demonstrate the utility of these data in informing nutrition research and policy., Background and History: Since 1971, NHANES, has been collecting information on the use of DSs from participants. These data are critical to national nutrition surveillance and have been used to characterize usage patterns, examine trends over time, assess the percentage of the population meeting or exceeding nutrient recommendations, and to help elucidate the sources contributing nutrients to the diet of the US population., Rationale: Over half of adults and about one-third of children in the United States use at least one dietary supplement in the past 30 days. Dietary supplements contribute to the dietary intake of nutrients and bioactive compounds in the US and therefore need to be assessed when monitoring nutritional status of the population and when studying diet-health associations., Recent Developments: With the recent development and availability of the Dietary Supplement Label Database (DSLD), a comprehensive DS database that will eventually contain labels for all products marketed in the US, NHANES DS data will be more easily linked to product information to estimate nutrient intake from DS., Future Directions: Over time, NHANES has both expanded and improved collection methods. The continued understanding of sources of error in collection methods will continue to be explored and is critical to improved accuracy., Conclusions: NHANES provides a rich source of nationally representative data on the usage of dietary supplements in the US., Competing Interests: Conflicts of interest and funding disclosure: J. J. Gahche, R.L. Bailey, N. Potischman, A.G. Ershow, K.A. Herrick, N. Ahluwalia have no conflicts of interest. J.T. Dwyer has stock in several drug companies, some of which may sell dietary supplements. There is no funding to disclose.

Background: Screen time (ST) behaviours, for example, television (TV) watching and computer use, among youth are associated with unhealthy eating, and these patterns track over time. A positive association between ST and TV watching with consumption of caffeinated foods and beverages has been described in national samples of children in a few European countries. The association of ST behaviours with caffeine intake has not been previously reported. We examined whether ST behaviours were associated with caffeine intake on a given day (% consumers and amount consumed) in a nationally representative sample of US children., Methods: Data on 3421 children (ages 6-11 years) from the cross-sectional National Health and Nutrition Examination Survey 2007-2012 were used. Time spent on TV watching and computer use was determined using questionnaires. Dietary intake was assessed using a 24-hour recall by trained interviewers. Caffeine intake (mg) was estimated by using updated food and nutrient databases. Caffeine consumption was examined in relation to time spent (≥2 vs<2 hours/day) on ST behaviours., Results: Children who watched TV ≥2 hours/day had significantly higher (~45% more) caffeine intake. Total ST or computer use was not associated with caffeine consumption in school-aged children., Conclusion: TV watching was positively associated with caffeine intake in school-aged children, suggesting the need for continued monitoring of ST and caffeine intake behaviours in children and adolescents as well as examining the correlates of these behaviours to inform nutrition and health policies., Competing Interests: Competing interests: None declared.

This corrects the article DOI: 10.1038/nm.4419.

Maladaptive wound healing responses to chronic tissue injury result in organ fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition and tissue remodeling by activated myofibroblasts, leads to loss of proper tissue architecture and organ function; however, the molecular mediators of myofibroblast activation have yet to be fully identified. Here we identify soluble ephrin-B2 (sEphrin-B2) as a new profibrotic mediator in lung and skin fibrosis. We provide molecular, functional and translational evidence that the ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar airspace after lung injury. Shedding of sEphrin-B2 promotes fibroblast chemotaxis and activation via EphB3 and/or EphB4 receptor signaling. We found that mice lacking ephrin-B2 in fibroblasts are protected from skin and lung fibrosis and that a disintegrin and metalloproteinase 10 (ADAM10) is the major ephrin-B2 sheddase in fibroblasts. ADAM10 expression is increased by transforming growth factor (TGF)-β1, and ADAM10-mediated sEphrin-B2 generation is required for TGF-β1-induced myofibroblast activation. Pharmacological inhibition of ADAM10 reduces sEphrin-B2 levels in bronchoalveolar lavage and prevents lung fibrosis in mice. Consistent with the mouse data, ADAM10-sEphrin-B2 signaling is upregulated in fibroblasts from human subjects with idiopathic pulmonary fibrosis. These results uncover a new molecular mechanism of tissue fibrogenesis and identify sEphrin-B2, its receptors EphB3 and EphB4 and ADAM10 as potential therapeutic targets in the treatment of fibrotic diseases.

Data System. The National Health and Nutrition Examination Survey (NHANES), conducted by the National Center for Health Statistics, is a cross-sectional survey on the health and nutritional status of US adults and children. Data Collection/Processing. A complex, multistage probability design is used to select a sample representative of the US civilian, noninstitutionalized population. NHANES includes in-home interviews, physical examinations, and biospecimen collection. About 5000 persons are examined annually. Since 2011, NHANES has been oversampling Asian Americans in addition to traditionally oversampled groups, including Hispanics and non-Hispanic Blacks. Data Analysis/Dissemination. Data are publicly released online in 2-year cycles. Some data, because of disclosure risk, are only available through the Research Data Center. Data users should read documentation, examine sample sizes and response rates, and account for the complex survey design. With publicly released data, analyses of Asians as a single group is only possible; some Asian subgroup analyses may be conducted through the Research Data Center. Public Health Implications. Oversampling Asians in NHANES 2011-2018 allows national estimates to be computed on health conditions, nutrition, and risk factors of public health importance on this growing subpopulation of Asian Americans.

Background: The consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular disease, and reducing their consumption is a major public health objective. Food intake studies have provided estimates for TFA concentrations in the US population; however, there is a need for data on TFA blood concentrations in the population. Objective: The objective of this study was to determine plasma TFA concentrations in a nationally representative group of fasted adults in the US population in NHANES samples from 1999-2000 and 2009-2010. Design: Four major TFAs [palmitelaidic acid (C16:1n-7t), trans vaccenic acid (C18:1n-7t), elaidic acid (C18:1n-9t), and linoelaidic acid (C18:2n-6t,9t)] were measured in plasma in 1613 subjects from NHANES 1999-2000 and 2462 subjects from NHANES 2009-2010 by gas chromatography-mass spectrometry. Geometric means and distribution percentiles were calculated for each TFA and their sum by age, sex, and race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American), and covariate-adjusted geometric means were computed by using a model that included these demographic and other dietary factors, as well as survey year and any significant interaction terms. Results: These nationally representative data for the adult US population show that TFA concentrations were 54% lower in NHANES 2009-2010 than in NHANES 1999-2000. Covariate-adjusted geometric means for the sum of the 4 TFAs were 81.4 μmol/L (95% CI: 77.3, 85.6 μmol/L) and 37.8 μmol/L (95% CI: 36.4, 39.4 μmol/L) in NHANES 1999-2000 and 2009-2010, respectively. Even with the large decline in TFA concentrations, differences between demographic subgroups were comparable in the 2 surveys. Conclusion: The results indicate an overall reduction in TFA concentrations in the US population and provide a valuable baseline to evaluate the impact of the recent regulation categorizing TFAs as food additives., (© 2017 American Society for Nutrition.)

A 37-year-old woman receiving in vitro fertilisation (IVF) treatment presented with lethargy, fevers and anuria. Her background included complex surgically managed Crohn's disease and mild right-sided hydronephrosis (with no evidence of obstruction on MAG3 renogram). On examination, she had a distended abdomen with generalised tenderness. Blood tests revealed an acute kidney injury and confirmed sepsis. She was found to have bilateral ureteric obstruction with worsening of the right-sided hydronephrosis and new-onset left-sided hydronephrosis secondary to bilateral ovarian masses, diagnosed as mild ovarian hyperstimulation syndrome (OHSS). She was initially managed with fluid resuscitation, bilateral nephrostomies, antibiotics and supportive management of mild OHSS. She made a good recovery and was discharged after placement of antegrade stents and removal of nephrostomies. On follow-up, following resolution of ovarian hyperstimulation, she has been diagnosed with a right-sided distal ureteric stricture and is awaiting reconstruction. Her left ureteric stent has been removed., Competing Interests: Conflicts of Interest: None declared., (2016 BMJ Publishing Group Ltd.)

Background: To our knowledge, few studies have described the usual nutrient intakes of US children aged <2 y or assessed the nutrient adequacy of their diets relative to the recommended Dietary Reference Intakes (DRIs)., Objective: We estimated the usual nutrient intake of US children aged 6-23 mo examined in NHANES 2009-2012 and compared them to age-specific DRIs as applicable., Design: Dietary intake was assessed with two 24-h recalls for infants aged 6-11 mo (n = 381) and toddlers aged 12-23 mo (n = 516) with the use of the USDA's Automated Multiple-Pass Method. Estimates of usual nutrient intakes from food and beverages were obtained with the use of the National Cancer Institute method. The proportions of children with intakes below and above the DRI were also estimated., Results: The estimated usual intakes of infants were adequate for most nutrients; however, 10% had an iron intake below the Estimated Average Requirement (EAR), and only 21% had a vitamin D intake that met or exceeded the recommended Adequate Intake (AI). More nutrient inadequacies were noted among toddlers; 1 in 4 had a lower-than-recommended fat intake (percentage of energy), and most had intakes that were below the EAR for vitamins E (82%) and D (74%). Few toddlers (<1%) met or exceeded the AI for fiber and potassium. In contrast, 1 in 2 had sodium intakes that exceeded the Tolerable Upper Intake Level (UL); ≥16% and 41% of the children had excessive intakes (greater than the ULs) of vitamin A and zinc, respectively., Conclusions: The estimated usual intakes of infants were adequate for most nutrients. Most toddlers were at risk for inadequate intakes of vitamins D and E and had diets low in fiber and potassium. The sources contributing to excessive intakes of vitamin A and zinc among infants and toddlers may need further evaluation., (© 2016 American Society for Nutrition.)

Pathologic accumulation of fibroblasts in pulmonary fibrosis appears to depend on their invasion through basement membranes and extracellular matrices. Fibroblasts from the fibrotic lungs of patients with idiopathic pulmonary fibrosis (IPF) have been demonstrated to acquire a phenotype characterized by increased cell-autonomous invasion. Here, we investigated whether fibroblast invasion is further stimulated by soluble mediators induced by lung injury. We found that bronchoalveolar lavage fluids from bleomycin-challenged mice or patients with IPF contain mediators that dramatically increase the matrix invasion of primary lung fibroblasts. Further characterization of this non-cell-autonomous fibroblast invasion suggested that the mediators driving this process are produced locally after lung injury and are preferentially produced by fibrogenic (e.g., bleomycin-induced) rather than nonfibrogenic (e.g., LPS-induced) lung injury. Comparison of invasion and migration induced by a series of fibroblast-active mediators indicated that these two forms of fibroblast movement are directed by distinct sets of stimuli. Finally, knockdown of multiple different membrane receptors, including platelet-derived growth factor receptor-β, lysophosphatidic acid 1, epidermal growth factor receptor, and fibroblast growth factor receptor 2, mitigated the non-cell-autonomous fibroblast invasion induced by bronchoalveolar lavage from bleomycin-injured mice, suggesting that multiple different mediators drive fibroblast invasion in pulmonary fibrosis. The magnitude of this mediator-driven fibroblast invasion suggests that its inhibition could be a novel therapeutic strategy for pulmonary fibrosis. Further elaboration of the molecular mechanisms that drive non-cell-autonomous fibroblast invasion consequently may provide a rich set of novel drug targets for the treatment of IPF and other fibrotic lung diseases.

Lysophosphatidic acid (LPA) is an important mediator of pulmonary fibrosis. In blood and multiple tumor types, autotaxin produces LPA from lysophosphatidylcholine (LPC) via lysophospholipase D activity, but alternative enzymatic pathways also exist for LPA production. We examined the role of autotaxin (ATX) in pulmonary LPA production during fibrogenesis in a bleomycin mouse model. We found that bleomycin injury increases the bronchoalveolar lavage (BAL) fluid levels of ATX protein 17-fold. However, the LPA and LPC species that increase in BAL of bleomycin-injured mice were discordant, inconsistent with a substrate-product relationship between LPC and LPA in pulmonary fibrosis. LPA species with longer chain polyunsaturated acyl groups predominated in BAL fluid after bleomycin injury, with 22:5 and 22:6 species accounting for 55 and 16% of the total, whereas the predominant BAL LPC species contained shorter chain, saturated acyl groups, with 16:0 and 18:0 species accounting for 56 and 14% of the total. Further, administration of the potent ATX inhibitor PAT-048 to bleomycin-challenged mice markedly decreased ATX activity systemically and in the lung, without effect on pulmonary LPA or fibrosis. Therefore, alternative ATX-independent pathways are likely responsible for local generation of LPA in the injured lung. These pathways will require identification to therapeutically target LPA production in pulmonary fibrosis.-Black, K. E., Berdyshev, E., Bain, G., Castelino, F. V., Shea, B. S., Probst, C. K., Fontaine, B. A., Bronova, I., Goulet, L., Lagares, D., Ahluwalia, N., Knipe, R. S., Natarajan, V., Tager, A. M. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis., (© FASEB.)

Purpose: Engaging in prolonged screen-time behaviors (STBs) is detrimental for health. The objective of the present analyses was to examine temporal trends in TV viewing and computer use among adolescents across 30 countries., Methods: Data were derived from the cross-national Health Behaviour in School-aged Children study. Data on TV viewing and computer use for gaming and nongaming purposes were collected in 2002 (n = 139,725 [51.4% girls]), 2006 (n = 149,251 [51.3% girls]), and 2010 (n = 154,845 [51.2% girls]). The temporal trends in TV viewing and computer use were each tested for all countries combined and for each individual country by sex-specific univariate analysis of variance., Results: Between 2002 and 2010, TV viewing decreased slightly in most of the 30 countries among both boys and girls. This decrease was more than offset by a sharp increase in computer use, which was consistent across all countries. Overall, boys reported more hours of STBs. They also reported a slightly larger decrease in TV viewing and slightly larger increase in computer use. STBs were generally more frequent on weekend days., Conclusions: The overall cross-national increases in STBs should be a call to action for public health practitioners, policy-makers, and researchers that interventions specifically focused on reducing STBs in youth are sorely needed. Because all countries experienced a trend in the same direction, it might be fruitful to learn more about the determinants of STBs among those countries in which hours of STBs are generally low as compared with other countries., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Breakfast is often considered the most important meal of the day and children and adolescents can benefit from breakfast consumption in several ways. The purpose of the present study was to describe trends in daily breakfast consumption (DBC) among adolescents across 31 countries participating in the HBSC survey between 2002 to 2010 and to identify socio-demographic (gender, family affluence and family structure) correlates of DBC. Cross-sectional surveys including nationally representative samples of 11-15 year olds (n = 455,391). Multilevel logistic regression analyses modeled DBC over time after adjusting for family affluence, family structure and year of survey. In all countries, children in two-parent families were more likely to report DBC compared to single parent families. In most countries (n = 19), DBC was associated with family affluence. Six countries showed an increase in DBC (Canada, Netherland, Macedonia, Scotland, Wales, England) from 2002. A significant decrease in DBC from 2002 was found in 11 countries (Belgium Fr, France, Germany, Croatia, Spain, Poland, Russian Federation, Ukraine, Latvia, Lithuania and Norway), while in 5 countries (Portugal, Denmark, Finland, Ireland, Sweden) no significant changes were seen. Frequency of DBC among adolescents in European countries and North America showed a more uniform pattern in 2010 as compared to patterns in 2002. DBC increased significantly in only six out of 19 countries from 2002 to 2010. There is need for continued education and campaigns to motivate adolescents to consume DBC. Comparing patterns across HBSC countries can make an important contribution to understanding regional /global trends and to monitoring strategies and development of health promotion programs.

Transoesophageal echocardiography (TOE) can be used to expedite DC cardioversion (DCCV) in the absence of adequate anticoagulation. There are no guidelines for the management of sedation or general anaesthetic. We performed a survey of NHS echocardiography departments to determine UK practice. Responses were received from 95 (50%) of 189 centres, and TOE-guided DCCV was performed in 81 centres. The numbers were <10 a year in 41 (50%), 10 - 50 in 31 (38%), 50 - 100 in 8 (10%) and >100 in 4 (5%) centres. Sedation for TOE was a usual practice in 67 (80%) centres but often temporally disconnected from DCCV due to logistical reasons. TOE under general anaesthetic was performed in 35 (43%) centres and as the usual method in 16 (20%). The patient was in the supine position with endotracheal intubation in 20 (57%) of centres, but without any form of airway protection while supine in 5 (14%). There is variability in practice across centres in the UK, in part due to limitations to services in most centres but also because of an absence of UK guidelines. The development of national standards may address this and aid in the development of local business cases to extend services., (© 2016 The authors.)

Objective: To evaluate the impact of interactive Nutri-Advice kiosks on children's nutritional skills and their ability to apply it to food choices in a middle school cafeteria menu (food choice competencies)., Design: Quasi-experimental design; pre/post-test., Setting: Freestanding interactive computer terminals (kiosks) were installed in three middle schools in Toulouse, France., Participants: A total of 580 children were enrolled into the study (mean age, 13 ± 1 years)., Intervention: Each child's physiological profile was stored in a personal barcode card. During 1 school year, once a day, each child could access the kiosk with this card, trying to find the most balanced meal according to his or her profile and the food available on the cafeteria menu., Main Outcome Measures: Children's food choice competency changes and body mass index z-score were evaluated., Analysis: Significance of change in food choice competencies (postintervention vs baseline) was examined using paired t test., Results: Across the study, children chose significantly less cheese and pastry or desserts, and significantly more starchy food and dairy, and tended to choose fruits and vegetables more often. Body mass index z-score decreased significantly during the period., Conclusions and Implications: Personalized nutrition counseling through an interactive device has the potential to improve the food choice competencies of children., (Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)