Tye7 regulates yeast Ty1 retrotransposon sense and antisense transcription in response to adenylic nucleotides stress

Transposable elements play a fundamental role in genome evolution. It is proposed that their mobility, activated under stress, induces mutations that could confer advantages to the host organism. Transcription of the Ty1 LTR-retrotransposon of Saccharomyces cerevisiae is activated in response to a severe deficiency in adenylic nucleotides. Here, we show that Ty2 and Ty3 are also stimulated under these stress conditions, revealing the simultaneous activation of three active Ty retrotransposon families. We demonstrate that Ty1 activation in response to adenylic nucleotide depletion requires the DNA-binding transcription factor Tye7. Ty1 is transcribed in both sense and antisense directions. We identify three Tye7 potential binding sites in the region of Ty1 DNA sequence where antisense transcription starts. We show that Tye7 binds to Ty1 DNA and regulates Ty1 antisense transcription. Altogether, our data suggest that, in response to adenylic nucleotide reduction, TYE7 is induced and activates Ty1 mRNA transcription, possibly by controlling Ty1 antisense transcription. We also provide the first evidence that Ty1 antisense transcription can be regulated by environmental stress conditions, pointing to a new level of control of Ty1 activity by stress, as Ty1 antisense RNAs play an important role in regulating Ty1 mobility at both the transcriptional and post-transcriptional stages

French vascular physicians’ practices in indicating antiplatelet and anticoagulation therapy in venous thromboembolism

International audienceBackground: As antiplatelet therapy becomes widespread, physicians face the issue patients being treated with antiplatelet agents (APA) and anticoagulants for venous thromboembolism (VTE). Bleeding risk of this combination is increased 1.5-2.5-fold. The aim of this survey is to assess French vascular physician's management of this combination at the beginning of the treatment and at 6 months of treatment for VTE. Patients and methods: French vascular physicians were surveyed between September and December 2017, using 4 fictional scenarios regarding a VTE event diagnosed in a patient under antiplatelet therapy plus isolated questions in an online questionnaire, sent by the French Society of Vascular Medicine to its members. Out of 1812 physicians, 179 returned valid questionnaires: the response rate was 9.9%. Results: Firstly 97.2% of respondents acknowledged extra risk with this combination; and 63% ceased antiplatelet therapy when initiating anticoagulants; while 36% did not. Secondly, four strategies emerged: 31.4% ceased APA and prescribed full-dose anticoagulants at initiation and at 6 months; 32% associated reduced-dose anticoagulation with APA at 6 months, regardless of what they decided at initiation; 16.5% prescribed isolated full-dose anticoagulants at initiation and reduced-dose at 6 months; lastly 11.2% associated full-dose anticoagulant with antiplatelet therapy at initiation and at 6 months. Conclusions: French vascular physicians adopted different strategies according to estimated risk/benefit ratio. Prospective randomized controlled trials should compare these strategies in order to make recommendations

International Guidelines for Hypertension: Resemblance, Divergence and Inconsistencies

High blood pressure is the number one killer in the world. About 1.5 billion people suffered from hypertension in 2010, and these numbers are increasing year by year. The basics of the management of high blood pressure are described in the Canadian, American, International and European guidelines for hypertension. However, there are similarities and differences in the definition, measurement and management of blood pressure between these different guidelines. According to the Canadian guidelines, normal blood pressure is less than 140/90 mmHg (systolic blood pressure/diastolic blood pressure). The AHA and ESC estimate normal blood pressure to be less than 120/80 mmHg (systolic blood pressure/diastolic blood pressure). Regarding treatments, the AHA, ISH and ESC are also in agreement about dual therapy as the first-line therapy, while Canadian recommendations retain the idea of monotherapy as the initiation of treatment. When it comes to measuring blood pressure, the four entities agree on the stratification of intervention in absolute cardiovascular risk

International Guidelines for Hypertension: Resemblance, Divergence and Inconsistencies

High blood pressure is the number one killer in the world. About 1.5 billion people suffered from hypertension in 2010, and these numbers are increasing year by year. The basics of the management of high blood pressure are described in the Canadian, American, International and European guidelines for hypertension. However, there are similarities and differences in the definition, measurement and management of blood pressure between these different guidelines. According to the Canadian guidelines, normal blood pressure is less than 140/90 mmHg (systolic blood pressure/diastolic blood pressure). The AHA and ESC estimate normal blood pressure to be less than 120/80 mmHg (systolic blood pressure/diastolic blood pressure). Regarding treatments, the AHA, ISH and ESC are also in agreement about dual therapy as the first-line therapy, while Canadian recommendations retain the idea of monotherapy as the initiation of treatment. When it comes to measuring blood pressure, the four entities agree on the stratification of intervention in absolute cardiovascular risk

Epidemiology of heart failure in young adults: a French nationwide cohort study

International audienceAims Heart failure (HF) in young adults is uncommon, and changes in its incidence and prognosis in recent years are poorly described. Methods and results The incidence and prognosis of HF in young adults (18–50 years) were characterized using nationwide medico-administrative data from the French National Hospitalization Database (period 2013–2018). A total of 1,486 877 patients hospitalized for incident HF were identified, including 70 075 (4.7%) patients aged 18–50 years (estimated incidence of 0.44‰ for this age group). During the study period, the overall incidence of HF tended to decrease in the overall population but significantly increased by ∼0.041‰ in young adults (P < 0.001). This increase was notably observed among young men (from 0.51‰ to 0.59‰, P < 0.001), particularly those aged 36–50 years. In these young men, ischaemic heart disease (IHD) was the most frequently reported cause of HF, whereas non-ischaemic HF was mainly observed in patients ≤ 35 years old. In contrast to non-ischaemic HF, the incidence of IHD increased over the study period, which suggests that IHD-related HF is progressively affecting younger patients. Concordantly, young HF patients presented with high rates of traditional IHD risk factors, including obesity, smoking, hypertension, dyslipidaemia, or diabetes. Lastly, the rates of re-hospitalization (for HF or for any cause) within two years after the first HF event and in-hospital mortality were high in all groups, indicating a poor-prognosis population. Conclusion Strategies for the prevention of HF risk factors should be strongly considered for patients under 50 years old

The Use of Telemedicine in Nursing Homes: A Mixed-Method Study to Identify Critical Factors When Connecting with a General Hospital

Evaluating the use and impact of telemedicine in nursing homes is necessary to promote improvements in the quality of this practice. Even though challenges and opportunities of telemedicine are increasingly becoming well documented for geriatrics (such as improving access to healthcare, patient management, and education while reducing costs), there is still limited knowledge on how to better implement it in an inter-organizational context, especially when considering nursing homes. In this regard, this study aimed first to describe the telemedicine activity of nursing homes when cooperating with a general hospital; and then understand the behavioral differences amongst nursing homes while identifying critical factors when implementing a telemedicine project. We conducted a sequential, explanatory mixed-method study using quantitative then qualitative methods to better understand the results. Three years of teleconsultation data of twenty-six nursing homes (15 rural and 11 urban) conducting teleconsultations with a general hospital (Troyes Hospital, France) were included for the quantitative analysis, and eleven telemedicine project managers for the qualitative analysis. Between April 2018 and April 2021, 590 teleconsultations were conducted: 45% (n = 265) were conducted for general practice, 29% (n = 172) for wound care, 11% (n = 62) for diabetes management, 8% (n = 47) with gerontologist and 6% (n = 38) for dermatology. Rural nursing homes conducted more teleconsultations overall than urban ones (RR: 2.484; 95% CI: 1.083 to 5.518; p = 0.03) and included more teleconsultations for general practice (RR: 16.305; 95% CI: 3.505 to 73.523; p = 0.001). Our qualitative study showed that three critical factors are required for the implementation of a telemedicine project in nursing homes: (1) the motivation to perform teleconsultations (in other words, improving access to care and cooperation between professionals); (2) building a relevant telemedicine medical offer based on patients’ and treating physicians’ needs; and (3) it’s specific organization in terms of time and space. Our study showed different uses of teleconsultations according to the rural or urban localization of nursing homes and that telemedicine projects should be designed to consider this aspect. Triggered by the COVID-19 pandemic, telemedicine projects in nursing homes are increasing, and observing the three critical factors presented above could be necessary to limit the failure of such projects

Retrotransposons. An RNA polymerase III subunit determines sites of retrotransposon integration.

International audienceMobile genetic elements are ubiquitous. Their integration site influences genome stability and gene expression. The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae integrates upstream of RNA polymerase III (Pol III)-transcribed genes, yet the primary determinant of target specificity has remained elusive. Here we describe an interaction between Ty1 integrase and the AC40 subunit of Pol III and demonstrate that AC40 is the predominant determinant targeting Ty1 integration upstream of Pol III-transcribed genes. Lack of an integrase-AC40 interaction dramatically alters target site choice, leading to a redistribution of Ty1 insertions in the genome, mainly to chromosome ends. The mechanism of target specificity allows Ty1 to proliferate and yet minimizes genetic damage to its host

Atrial Fibrillation Detection With an Analog Smartwatch: Prospective Clinical Study and Algorithm Validation

BackgroundAtrial fibrillation affects approximately 4% of the world’s population and is one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity. It can be difficult to diagnose when asymptomatic or in the paroxysmal stage, and its natural history is not well understood. New wearables and connected devices offer an opportunity to improve on this situation. ObjectiveWe aimed to validate an algorithm for the automatic detection of atrial fibrillation from a single-lead electrocardiogram taken with a smartwatch. MethodsEligible patients were recruited from 4 sites in Paris, France. Electrocardiograms (12-lead reference and single lead) were captured simultaneously. The electrocardiograms were reviewed by independent, blinded board-certified cardiologists. The sensitivity and specificity of the algorithm to detect atrial fibrillation and normal sinus rhythm were calculated. The quality of single-lead electrocardiograms (visibility and polarity of waves, interval durations, heart rate) was assessed in comparison with the gold standard (12-lead electrocardiogram). ResultsA total of 262 patients (atrial fibrillation: n=100, age: mean 74.3 years, SD 12.3; normal sinus rhythm: n=113, age: 61.8 years, SD 14.3; other arrhythmia: n=45, 66.9 years, SD 15.2; unreadable electrocardiograms: n=4) were included in the final analysis; 6.9% (18/262) were classified as Noise by the algorithm. Excluding other arrhythmias and Noise, the sensitivity for atrial fibrillation detection was 0.963 (95% CI lower bound 0.894), and the specificity was 1.000 (95% CI lower bound 0.967). Visibility and polarity accuracies were similar (1-lead electrocardiogram: P waves: 96.9%, QRS complexes: 99.2%, T waves: 91.2%; 12-lead electrocardiogram: P waves: 100%, QRS complexes: 98.8%, T waves: 99.5%). P-wave visibility accuracy was 99% (99/100) for patients with atrial fibrillation and 95.7% (155/162) for patients with normal sinus rhythm, other arrhythmias, and unreadable electrocardiograms. The absolute values of the mean differences in PR duration and QRS width were <3 ms, and more than 97% were <40 ms. The mean difference between the heart rates from the 1-lead electrocardiogram calculated by the algorithm and those calculated by cardiologists was 0.55 bpm. ConclusionsThe algorithm demonstrated great diagnostic performance for atrial fibrillation detection. The smartwatch’s single-lead electrocardiogram also demonstrated good quality for physician use in daily routine care. Trial RegistrationClinicalTrials.gov NCT04351386; http://clinicaltrials.gov/ct2/show/NCT0435138

Cardiac performance in patients hospitalized with COVID‐19: a 6 month follow‐up study

Abstract Aims Myocardial injury is frequently observed in patients hospitalized with coronavirus disease 2019 (COVID‐19) pneumonia. Different cardiac abnormalities have been reported during the acute COVID‐19 phase, ranging from infra‐clinic elevations of myocardial necrosis biomarkers to acute cardiac dysfunction and myocarditis. There is limited information on late cardiac sequelae in patients who have recovered from acute COVID‐19 illness. We aimed to document the presence and quantify the extent of myocardial functional alterations in patients hospitalized 6 months earlier for COVID‐19 infection. Methods and results We conducted a prospective echocardiographic evaluation of 48 patients (mean age 58 ± 13 years, 69% male) hospitalized 6 ± 1 month earlier for a laboratory‐confirmed and symptomatic COVID‐19. Thirty‐two (66.6%) had pre‐existing cardiovascular risks factors (systemic hypertension, diabetes, or dyslipidaemia), and three patients (6.2%) had a known prior myocardial infarction. Sixteen patients (33.3%) experienced myocardial injury during the index COVID‐19 hospitalization as identified by a rise in cardiac troponin levels. Six months later, 60.4% of patients still reported clinical symptoms including exercise dyspnoea for 56%. Echocardiographic measurements under resting conditions were not different between patients with versus without myocardial injury during the acute COVID‐19 phase. In contrast, low‐level exercise (25W for 3 min) induced a significant increase in the average E/e′ ratio (10.1 ± 4.3 vs. 7.3 ± 11.5, P = 0.01) and the systolic pulmonary artery pressure (33.4 ± 7.8 vs. 25.6 ± 5.3 mmHg, P = 0.02) in patients with myocardial injury during the acute COVID‐19 phase. Sensitivity analyses showed that these alterations of left ventricular diastolic markers were observed regardless of whether of cardiovascular risk factors or established cardiac diseases indicating SARS‐CoV‐2 infection as a primary cause. Conclusions Six months after the acute COVID‐19 phase, significant cardiac diastolic abnormalities are observed in patients who experienced myocardial injury but not in patients without cardiac involvement

Cardiac performance in patients hospitalized with COVID‐19: a 6 month follow‐up study

International audienceAims: Myocardial injury is frequently observed in patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. Different cardiac abnormalities have been reported during the acute COVID-19 phase, ranging from infra-clinic elevations of myocardial necrosis biomarkers to acute cardiac dysfunction and myocarditis. There is limited information on late cardiac sequelae in patients who have recovered from acute COVID-19 illness. We aimed to document the presence and quantify the extent of myocardial functional alterations in patients hospitalized 6 months earlier for COVID-19 infection.Methods and results: We conducted a prospective echocardiographic evaluation of 48 patients (mean age 58 ± 13 years, 69% male) hospitalized 6 ± 1 month earlier for a laboratory-confirmed and symptomatic COVID-19. Thirty-two (66.6%) had pre-existing cardiovascular risks factors (systemic hypertension, diabetes, or dyslipidaemia), and three patients (6.2%) had a known prior myocardial infarction. Sixteen patients (33.3%) experienced myocardial injury during the index COVID-19 hospitalization as identified by a rise in cardiac troponin levels. Six months later, 60.4% of patients still reported clinical symptoms including exercise dyspnoea for 56%. Echocardiographic measurements under resting conditions were not different between patients with versus without myocardial injury during the acute COVID-19 phase. In contrast, low-level exercise (25W for 3 min) induced a significant increase in the average E/e' ratio (10.1 ± 4.3 vs. 7.3 ± 11.5, P = 0.01) and the systolic pulmonary artery pressure (33.4 ± 7.8 vs. 25.6 ± 5.3 mmHg, P = 0.02) in patients with myocardial injury during the acute COVID-19 phase. Sensitivity analyses showed that these alterations of left ventricular diastolic markers were observed regardless of whether of cardiovascular risk factors or established cardiac diseases indicating SARS-CoV-2 infection as a primary cause.Conclusions: Six months after the acute COVID-19 phase, significant cardiac diastolic abnormalities are observed in patients who experienced myocardial injury but not in patients without cardiac involvement