The Role of Histone H4 Biotinylation in the Structure of Nucleosomes

Background: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation. Methodology/Principal Findings: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA wrapped around the histone core in nucleosomes with biotinylated H4. This statistically significant (p,0.001) difference between native and biotinylated nucleosomes corresponds to adding approximately 20 bp to the classical 147 bp length of nucleosomal DNA. Conclusions/Significance: The increase in nucleosomal DNA length is predicted to stabilize the association of DNA with histones and therefore to prevent nucleosomes from unwrapping. This provides a mechanistic explanation for the gene silencing associated with K12Bio-H4. The proposed single-molecule AFM approach will be instrumental for studying the effects of various epigenetic modifications of nucleosomes, in addition to biotinylation

Renal dysfunction and outcome in left ventricular non-compaction

Background: While renal function has been observed to inversely correlate with clinical outcome in other cardiomyopathies, its prognostic significance in patients with left ventricular non-compaction cardiomyopathy (LVNC) has not been investigated. The aim of this study was to determine the prognostic value of renal function in LVNC patients. Methods: Patients with isolated LVNC as diagnosed by echocardiography and/or magnetic resonance imaging in 4 Swiss centers were retrospectively analyzed for this study. Values for creatinine, urea, and estimated glomerular filtration rate (eGFR) as assessed by the CKD-EPI 2009 formula were collected and analyzed by a Cox regression model for the occurrence of a composite endpoint (death or heart transplantation). Results: During the median observation period of 7.4 years 23 patients reached the endpoint. The age- and gender-corrected hazard ratios (HR) for death or heart transplantation were: 1.9 (95% confidence interval [CI] 1.4–2.6) for each increase over baseline creatinine level of 30 µmol/L (p < 0.001), 1.6 (95% CI 1.2–2.2) for each increase over baseline urea level of 5 mmol/L (p = 0.004), and 3.6 (95% CI 1.9–6.9) for each decrease below baseline eGFR level of 30 mL/min (p ≤ 0.001). The HR (log2) for every doubling of creatinine was 7.7 (95% CI 3–19.8; p < 0.001), for every doubling of urea 2.5 (95% CI 1.5–4.3; p < 0.001), and for every bisection of eGFR 5.3 (95% CI 2.4–11.6; p < 0.001). Conclusions: This study provides evidence that in patients with LVNC impairment in renal function is associated with an increased risk of death and heart transplantation suggesting that kidney function assessment should be standard in risk assessment of LVNC patients

A systematic review of contamination (aerosol, splatter and droplet generation) associated with oral surgery and its relevance to COVID-19

IntroductionThe current COVID-19 pandemic caused by the SARS-CoV-2 virus has impacted the delivery of dental care globally and has led to re-evaluation of infection control standards. However, lack of clarity around what is known and unknown regarding droplet and aerosol generation in dentistry (including oral surgery and extractions), and their relative risk to patients and the dental team, necessitates a review of evidence relating to specific dental procedures. This review is part of a wider body of research exploring the evidence on bioaerosols in dentistry and involves detailed consideration of the risk of contamination in relation to oral surgery.MethodsA comprehensive search of Medline (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, Scopus, Web of Science, LILACS and ClinicalTrials.Gov was conducted using key terms and MeSH (Medical Subject Headings) words relating to the review questions. Methodological quality including sensitivity was assessed using a schema developed to measure quality aspects of studies using a traffic light system to allow inter- and intra-study overview and comparison. A narrative synthesis was conducted for assessment of the included studies and for the synthesis of results.ResultsEleven studies on oral surgery (including extractions) were included in the review. They explored microbiological (bacterial and fungal) and blood (visible and/or imperceptible) contamination at the person level (patients, operators and assistants) and/or at a wider environmental level, using settle plates, chemiluminescence reagents or air samplers; all within 1 m of the surgical site. Studies were of generally low to medium quality and highlighted an overall risk of contaminated aerosol, droplet and splatter generation during oral surgery procedures, most notably during removal of impacted teeth using rotatory handpieces. Risk of contamination and spread was increased by factors, including proximity to the operatory site, longer duration of treatment, higher procedural complexity, non-use of an extraoral evacuator and areas involving more frequent contact during treatment.ConclusionA risk of contamination (microbiological, visible and imperceptible blood) to patients, dental team members and the clinical environment is present during oral surgery procedures, including routine extractions. However, the extent of contamination has not been explored fully in relation to time and distance. Variability across studies with regards to the analysis methods used and outcome measures makes it difficult to draw robust conclusions. Further studies with improved methodologies, including higher test sensitivity and consideration of viruses, are required to validate these findings

Coffee, Alcohol, Smoking, Physical Activity and QT Interval Duration: Results from the Third National Health and Nutrition Examination Survey

Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration.We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988-1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview.In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were -1.2 ms (95% CI -4.4 to 2.0) for coffee, and -2.0 ms (-11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (-0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (-0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (-2.9 to 5.2) and 1.7 ms (-2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was -0.8 ms (-3.0 to 1.4).Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity

Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry

Aims: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). Methods and results: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50\u20133.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78\u20131.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. Conclusion: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.The International Takotsubo Registry was supported by the Biss Davies Charitable Trust. Dr. Scheitz has been supported by the Corona Foundation. Dr. Templin has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation.info:eu-repo/semantics/publishedVersio

Ethnic comparison in takotsubo syndrome : novel insights from the International Takotsubo Registry

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.Open Access funding provided by Universität Zürich. CT has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. has been supported by EU HORIZON 2020 (SILICOFCM ID777204). J.R.G has received a grant “Filling the gap” from the University of Zurich. The InterTAK Registry is supported by The Biss Davies Charitable Trust.info:eu-repo/semantics/publishedVersio

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Cardiac arrest in takotsubo syndrome: Results from the InterTAK Registry

Aims: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS).Methods and results: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P Conclusions: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.</p