Sleep apnoea and the heart

Sleep apnoea is associated with significant daytime functioning impairment and marked cardiovascular morbidities, leading to a significant increase in mortality. Sympathetic activation, oxidative stress and systemic inflammation have been shown to be the main intermediary mechanisms associated with sleep apnoea and intermittent hypoxia. There are now convincing data regarding the association between hypertension, arrhythmias, coronary heart disease, heart failure, increased cardiovascular mortality and sleep apnoea. This has been evidenced in sleep apnoea patients and is supported by experimental data obtained in intermittent hypoxia. Whether treating sleep apnoea enables chronic cardiovascular consequences to be reversed is not fully established as regard coronary heart disease, arrhythmias and heart failure. In this late condition, complex bidirectional relationships occur, with obstructive sleep apnoea being a risk factor for heart failure whilst central sleep apnoea mainly appears as a consequence of heart failure. It remains to be established in adequately designed studies, i.e. large randomised controlled trials, whether treating sleep apnoea can improve heart failure morbidity and mortality

Toll-Like Receptor-4 Mediated Inflammation Is Involved in the Cardiometabolic Alterations Induced by Intermittent Hypoxia

Objective. Intermittent hypoxia (IH) is a major component of sleep apnea syndrome as its cardiometabolic complications have been mainly attributed to IH. The pathophysiology is still poorly understood but there are some similarities with the obesity-associated cardiometabolic complications. As the latter results from inflammation involving toll-like receptor-4 (TLR4) signaling, we assessed this pathway in the cardiometabolic consequences of IH. Methods. Lean adult male TLR4-deficient (TLR4−/−) mice and their controls (C57BL/6 mice) were exposed to either IH (FiO2 21-5%, 1 min cycle, 8 h/day) or air (normoxic mice) for 4 weeks. Animals were assessed at 1-week exposure for insulin tolerance test and after 4-week exposure for morphological and inflammatory changes of the epididymal fat and thoracic aorta. Results. IH induced insulin resistance, morphological and inflammatory changes of the epididymal fat (smaller pads and adipocytes, higher release of TNF-α and IL-6) and aorta (larger intima-media thickness and higher NFκB-p50 activity). All these alterations were prevented by TLR4 deletion. Conclusion. IH induces metabolic and vascular alterations that involve TLR4 mediated inflammation. These results confirm the important role of inflammation in the cardiometabolic consequences of IH and suggest that targeting TLR4/NFκB pathway could represent a further therapeutic option for sleep apnea patients

Exploring the Onset of a Male-Biased Interpretation of Masculine Generics Among French Speaking Kindergarten Children

In French, and other gender marked languages, there are two ways to interpret a grammatical masculine form when used to refer to social roles or occupations [e.g., les magiciens (the magiciansmasculine)]. It can refer to a group composed of only men (specific use of the masculine form), or one composed of both women and men (generic use). Studies of adults revealed that the rule that masculine forms can be interpreted as inclusive of either gender is not readily applied. To gain a better understanding of the processes shaping this phenomenon, we present a follow-up study (N = 52) to Lévy et al. (2016) to explore how French-speaking kindergarten children (3–5 years of age) resolve the semantic ambiguity of the grammatical masculine form when presented with role or occupation nouns. In a paradigm where participants’ gazes were monitored, children were presented with pictures of a pair of two boys and a pair of one girl and one boy and were prompted to Look at the [role nounmasculinepluralform]. First, the results suggest a stereotype effect in that children more strongly directed their gaze toward the boy-boy picture for stereotypical male role nouns, but toward the girl-boy picture for stereotypical female role nouns. Second, in the non-stereotypical/neutral condition we did not find an indication of any own-sex preference (as in Lévy et al., 2016), but of an influence of the role nouns’ grammatical gender, in that children more strongly directed their gaze toward boy-boy pictures than toward girl-boy pictures. We suggest that a specific interpretation of masculine forms might already start to emerge between 3 and 5 years of age, while gender stereotypes are still activated

Mission sur l’écosystème de la recherche et de l’innovation 14 propositions pour engager le processus de rénovation et de simplification de l’écosystème national Rapport à Madame la Ministre de l’Enseignement supérieur et de la Recherche

Mme la Ministre Sylvie Retailleau a confié à M. Philippe Gillet cette mission par lettre en date du 1er décembre 2022 (voir annexe). Après une phase de cadrage, les travaux ont été menés par l’ensemble du groupe de travail composé de Mmes Christine Cherbut et Véronique Perdereau et MM. Yves Caristan et Patrick Lévy de janvier à mai 2023. Les membres de la mission ont été appuyés par un inspecteur général de l’éducation, du sport et de la recherche, M. Charles Persoz. Cette mission s’est inscrite dans un contexte évolutif : la LPR a eu des conséquences récentes, plusieurs programmes stratégiques ont été initiés quelques mois ou quelques semaines avant le démarrage de la mission, comme les PEPR, les PUI, le programme de recherche à risque

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

ERS/ESH TASK FORCE REPORT Recommendations for the management of patients with obstructive sleep apnoea and hypertension

on behalf of the EU COST Action B26 members ABSTRACT: This article is aimed at addressing the current state-of-the-art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnoea (OSA) in cardiovascular (in particular hypertensive) patients, as well as for the management of cardiovascular diseases (in particular arterial hypertension) in OSA patients. The present document is the result of work performed by a panel of experts participating in the European Union COST (Cooperation in Scientific and Technological research) Action B26 on OSA, with the endorsement of the European Respiratory Society and the European Society of Hypertension. In particular, these recommendations are aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are also aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night

Self-assembly of liquid crystal block copolymer PEG-b-smectic polymer in pure state and in dilute aqueous solution

A series of amphiphilic LC block copolymers, in which the hydrophobic block is a smectic polymer poly(4-methoxyphenyl 4-(6-acryloyloxy-hexyloxy)-benzoate) (PA6ester1) and the hydrophilic block is polyethyleneglycol (PEG), were synthesized and characterized. The self-assembly of one of them in both the pure state and the dilute aqueous solution was investigated in detail. Nano-structures in the pure state were studied by SAXS and WAXS on samples aligned by a magnetic field. A hexagonal cylindrical micro-segregation phase was observed with a lattice distance of 11.2 nm. The PEG blocks are in the cylinder, while the smectic polymer blocks form a matrix with layer spacing 2.4 nm and layer normal parallel to the long axis of the cylinders. Faceted unilamellar polymer vesicles, polymersomes, were formed in water, as revealed by cryo-TEM. In the lyotropic bilayer membrane of these polymersomes, the thermotropic smectic order in the hydrophobic block is clearly visible with layer normal parallel to the membrane surface

International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club

Background: Patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. Methods: The international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. Results: In the following domains there was strong consensus: (1) the risk of pancreatic cancer in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations is high enough to justify surveillance; (2) the risk of pancreatic cancer in patients with CP associated with SPINK1 p. N34S is not high enough to justify surveillance; (3) surveillance should be undertaken in pancreatic specialist centers; (4) surveillance should only be introduced after the age of 40 years and stopped when the patient would no longer be suitable for surgical intervention. All patients with CP should be advised to lead a healthy lifestyle aimed at avoiding risk factors for progression of CP and pancreatic cancer. There was only moderate or weak agreement on the best methods of screening and surveillance in other types of environmental, familial and genetic forms of CP. Conclusions: Patients with inherited PRSS1 mutations should undergo surveillance for pancreatic cancer, but the best methods for cancer detection need further investigation

Ann Intensive Care

Unlike for septic shock, there are no specific international recommendations regarding the management of cardiogenic shock (CS) in critically ill patients. We present herein recommendations for the management of cardiogenic shock in adults, developed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF)), with the participation the French Society of Anesthesia and Intensive Care (SFAR), the French Cardiology Society (SFC), the French Emergency Medicine Society (SFMU), and the French Society of Thoracic and Cardiovascular Surgery (SFCTCV). The recommendations cover 15 fields of application such as: epidemiology, myocardial infarction, monitoring, vasoactive drugs, prehospital care, cardiac arrest, mechanical assistance, general treatments, cardiac surgery, poisoning, cardiogenic shock complicating end-stage cardiac failure, post-shock treatment, various etiologies, and medical care pathway. The experts highlight the fact that CS is a rare disease, the management of which requires a multidisciplinary technical platform as well as specialized and experienced medical teams. In particular, each expert center must be able to provide, at the same site, skills in a variety of disciplines, including medical and interventional cardiology, anesthesia, thoracic and vascular surgery, intensive care, cardiac assistance, radiology including for interventional vascular procedures, and a circulatory support mobile unit