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Mitochondrial dynamics, such as fusion and fission, play a critical role in maintaining cellular metabolic homeostasis. The molecular mechanisms underlying these processes include fusion proteins (Mitofusin 1 [MFN1], Mitofusin 2 [MFN2], and optic atrophy 1 [OPA1]) and fission mediators (mitochondrial fission 1 [FIS1] and dynamin-related protein 1 [DRP1]), which interact with each other to ensure mitochondrial quality control. Interestingly, defects in these proteins can lead to the loss of mitochondrial DNA (mtDNA) integrity, impairment of mitochondrial function, a severe alteration of mitochondrial morphology, and eventually cell death. Emerging evidence has revealed a causal relationship between dysregulation of mitochondria dynamics and age-associated type 2 diabetes, a metabolic disease whose rates have reached an alarming epidemic-like level with the majority of cases (59%) recorded in men aged 65 and over. In this sense, fragmentation of mitochondrial networks is often associated with defects in cellular energy production and increased apoptosis, leading, in turn, to excessive reactive oxygen species release, mitochondrial dysfunction, and metabolic alterations, which can ultimately contribute to beta-cell dysfunction and insulin resistance. The present review discusses the processes of mitochondrial fusion and fission and their dysfunction in type 2 diabetes, with special attention given to the therapeutic potential of targeting mitochondrial dynamics in this complex metabolic disorder.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociacion Latinoamericana de Torax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results: 1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians. © 2022 by the American Thoracic Society

BACKGROUND AND OBJECTIVES: The prevalence of atrial fibrillation (AF) and ischaemic heart disease (IHC) increases with age. They coexist in up to 20% of octogenarian patients, a situation that poses a therapeutic challenge. Trials that have addressed this scenario, which included a low percentage of octogenarians, showed that double therapy (single antiplatelet+anticoagulation) compared to triple therapy (double antiplatelet+anticoagulation) was associated with less bleeding events, especially with direct oral anticoagulants. These studies did not have sufficient power to detect differences in ischaemic events. On the other hand, prevalent characteristics in the elderly, such as geriatric syndromes, were not assessed in these studies, and are not usually evaluated in clinical practice. Accordingly, their prognostic impact remains unknown in this clinical context. METHODS: Observational, prospective, and multicentre study that will include patients =80 years with AF and IHC in Spain. Baseline characteristics and geriatric syndromes will be assessed, as well as the choice of antithrombotic treatment. The primary endpoint is cardiovascular and overall mortality at one and three years follow-up. RESULTS: This study will assess both characteristics and prognosis of octogenarian patients with AF and IHC in Spain, the factors involved in the choice of antithrombotic treatment, and the incidence of ischaemic and haemorrhagic events during the short- and long-term follow-up. CONCLUSION: This study will contribute to improve the knowledge in terms of safety and efficacy of the different therapeutic options in older patients with AF and IHC, as well as their prognostic impact.

The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy. (C) 2020 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

International audience; We sought datasets with granular age distributions of rotavirus-positive disease presentations among children

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic beta-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

During the last few years, the number of patients receiving anticoagulant and antiplatelet therapy has increased worldwide. Since this is a chronic treatment, patients receiving it can be expected to need some kind of surgery or intervention during their lifetime that may require treatment discontinuation. The decision to withdraw antithrombotic therapy depends on the patient's thrombotic risk versus hemorrhagic risk. Assessment of both factors will show the precise management of anticoagulant and antiplatelet therapy in these scenarios. The aim of this consensus document, coordinated by the Cardiovascular Thrombosis Working Group of the Spanish Society of Cardiology, and endorsed by most of the Spanish scientific societies of clinical specialities that may play a role in the patient-health care process during the perioperative or periprocedural period, is to recommend some simple and practical guidelines with a view to homogenizing daily clinical practice. Full English text available from: www.revespcardiol.org/en (C) 2018 Sociedad Espafiola de Cardiologia. Published by Elsevier Espania, S.L.U. All rights reserved.

Background: Several bleeding risk scores have been validated in patients with atrial fibrillation (AF). The ORBIT score has been recently proposed as a simple score with the best ability to predict major bleeding. The present study aimed to test the hypothesis that the ORBIT score was superior to the HAS-BLED score for predicting major bleeding and death in "real world" anticoagulated AF patients. Methods and Results: We analyzed the predictive performance for bleeding and death of 406 AF patients who underwent 571 electrical cardioversion procedures and 1,276 patients with permanent/persistent AF from the FANTASIIA registry. In the cardioversion population, 21 patients had major bleeding events and 26 patients died. The predictive performance for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.77 (95% CI 0.66-0.88) and 0.82 (95% CI 0.77-0.93), respectively; P=0.080). For the FANTASIIA population, 46 patients had major bleeding events and 50 patients died. The predictive performances for major bleeding of HASBLED and ORBIT were not significantly different (c-statistics 0.63 (95% CI 0.56-0.71) and 0.70 (95% CI 0.62-0.77), respectively; P=0.116). For death, the predictive performances of HAS-BLED and ORBIT were not significantly different in both populations. The ORBIT score categorized most patients as "low risk". Conclusions: Despite the original claims in its derivation paper, the ORBIT score was not superior to HAS-BLED for predicting major bleeding and death in a "real world" oral anticoagulated AF population.

BackgroundVitamin K antagonists (VKA) have a narrow therapeutic range, and literature analysis reveals poor quality of anticoagulation control. We sought to assess the prevalence of poor anticoagulant control in patients under VKA treatment in the prevention of stroke for atrial fibrillation (AF). HypothesisControl of anticoagulation with VKA is inadequate in a high percentage of patients with AF. MethodsPatients with AF under VKA treatment were prospectively recruited in this observational registry. The sample comprised 948 patients. The estimated time spent in the therapeutic range (TTR) was calculated, and variables related with a TTR >65% were analyzed. ResultsMean age was 73.8 9.4 years, and 42.5% of the patients were women. Mean TTR was 63.77% +/- 23.80% for the direct method and 60.27% +/- 24.48% for the Rosendaal method. Prevalence of poor anticoagulation control was 54%. Variables associated with good anticoagulation control were university studies (odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.08-3.64), chronic hepatic disease (OR: 8.15, 95% CI: 1.57-42.24), low comorbidity expressed as Charlson index (OR: 0.87, 95% CI: 0.76-0.99), no previous cardiac disease (OR: 0.64, 95% CI: 0.41-0.98), lower risk of bleeding assessed as hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly age, and use of drugs or alcohol (HAS-BLED; OR: 0.81, 95% CI: 0.69-0.95), and lower heart rate (OR: 0.99, 95% CI: 0.98-0.99). Conclusions Patients who receive VKA to prevent stroke for AF spend less than half the time within therapeutic range.

BackgroundVitamin K antagonists (VKA) have a narrow therapeutic range, and literature analysis reveals poor quality of anticoagulation control. We sought to assess the prevalence of poor anticoagulant control in patients under VKA treatment in the prevention of stroke for atrial fibrillation (AF). HypothesisControl of anticoagulation with VKA is inadequate in a high percentage of patients with AF. MethodsPatients with AF under VKA treatment were prospectively recruited in this observational registry. The sample comprised 948 patients. The estimated time spent in the therapeutic range (TTR) was calculated, and variables related with a TTR >65% were analyzed. ResultsMean age was 73.8 9.4 years, and 42.5% of the patients were women. Mean TTR was 63.77% +/- 23.80% for the direct method and 60.27% +/- 24.48% for the Rosendaal method. Prevalence of poor anticoagulation control was 54%. Variables associated with good anticoagulation control were university studies (odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.08-3.64), chronic hepatic disease (OR: 8.15, 95% CI: 1.57-42.24), low comorbidity expressed as Charlson index (OR: 0.87, 95% CI: 0.76-0.99), no previous cardiac disease (OR: 0.64, 95% CI: 0.41-0.98), lower risk of bleeding assessed as hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly age, and use of drugs or alcohol (HAS-BLED; OR: 0.81, 95% CI: 0.69-0.95), and lower heart rate (OR: 0.99, 95% CI: 0.98-0.99). Conclusions Patients who receive VKA to prevent stroke for AF spend less than half the time within therapeutic range.

Automatic quantification of cardiac muscle properties in tissue sections might provide important information related to different types of diseases. Second harmonic generation (SHG) imaging provides a stain-free microscopy approach to image cardiac fibers that, combined with our methodology of the automated measurement of the ultrastructure of muscle fibers, computes a reliable set of quantitative image features (sarcomere length, A-band length, thick-thin interaction length, and fiber orientation). We evaluated the performance of our methodology in computer-generated muscle fibers modeling some artifacts that are present during the image acquisition. Then, we also evaluated it by comparing it to manual measurements in SHG images from cardiac tissue of fetal and adult rabbits. The results showed a good performance of our methodology at high signal-to-noise ratio of 20 dB. We conclude that our automated measurements enable reliable characterization of cardiac fiber tissues to systematically study cardiac tissue in a wide range of conditions.

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure.

The nutrition of athletes has been of interest to scientists for decades and since the origins of sports competitions the questions about what to eat and what to drink in order to improve performance have been raised. Today there are scientific proofs that an adequate dietary habits influences in a large extent to an athlete's health, body composition, and energetic pathways during the activity as well as during the competition or recovery. Athletes should be well informed about the food groups, caloric intake, and daily meal schedule. As the previous investigations showed, the athletes obtain most of their knowledge about nutrition from their coaches, especially physical conditioning coaches (Burns et al, 2004 ; Jacobsson et al., 2001). The major aim of this study would be determination of the level of knowledge about nutrition and dietary habits, especially healthy way of eating in tennis coaches. Also the aim is to establish the relations between knowledge about nutrition and dietary habits. The sample consisted of 49 tennis coaches from Croatia. The knowledge about the sports nutrition and their dietary habits were tested by means of questionnaires. The questionnaires were constructed based on the results of previous studies conducted at the Faculty of Kinesiology (Mišigoj-Duraković et al, 2005) and the results from international studies (Conkle and Tischler, 1992 ; Parmenter and Wardle, 1999 ; Turconi et al., 2003 ; Paugh, 2005.). The questionnaire that provided information about knowledge in sports nutrition consisted of items determining the general knowledge about nutrition, nutritional ingredients needed for providing adequate energy level in sports, items about supplements, meal schedule before training and competition and recovery, and of items testing the knowledge about importance of liquids, dehydration and rehydration during and after training and competition. Dietary habits of the subjects were determined by items regarding the number of meals per day, skipping the meals, intake of particular food subgroups based on the food pyramid, liquid intake and vitamin and mineral supplements intake, specially those used usually in sports. Surveys were anonymous and the data obtained were analysed by statistical software STATISTICA for WINDOWS. The correlations between nutritional knowledge and dietary habits were tested by Pearson correlation coefficient. According to the results obtained we concluded that the level of knowledge about nutrition and dietary habits of tennis coaches are inadequate and that the source of information for nutritional facts that they use are not always scientifically justified. Positive relationship was found between dietary habits and nutritional knowledge. Good level of knowledge potentially could indicate good dietary habits.