Sex-Based Difference in Aortic Dissection Outcomes: A Multicenter Study

Background: Type A Acute Aortic Dissection (TAAAD) repair is a surgical emergency associated with high morbidity and mortality. Registry data have noted several sex-specific differences in presentation with TAAAD which may account for the differences in men and women undergoing surgery for this condition. Methods: A retrospective review of data from three departments of cardiac surgery (Centre Cardiologique du Nord, Henri-Mondor University Hospital, San Martino University Hospital, Genoa) between January 2005 and 31 December 2021 was conducted. Confounders were adjusted using doubly robust regression models, a combination of regression models with inverse probability treatment weighting by propensity score. Results: 633 patients were included in the study, of which 192 (30.3%) were women. Women were significantly older with reduced haemoglobin levels and pre-operative estimated glomerular filtration rate compared to men. Male patients were more likely to undergo aortic root replacement and partial or total arch repair. Operative mortality (OR 0.745, 95% CI: 0.491–1.130) and early postoperative neurological complication results were comparable between the groups. The adjusted survival curves using IPTW by propensity score confirmed the absence of a significant impact of gender on long-term survival (HR 0.883, 95% CI 0.561–1.198). In a subgroup analysis of women, preoperative levels of arterial lactate (OR 1.468, 95% CI: 1.133–1.901) and mesenteric ischemia after surgery (OR 32.742, 95% CI: 3.361–319.017) were significantly associated with increased operative mortality. Conclusions: The advancing age of female patients alongside raised preoperative level of arterial lactate may account for the increasing preponderance among surgeons to perform more conservative surgery compared to their younger male counterparts although postoperative survival was similar between the groups

A double blind randomized trial of wound infiltration with ropivacaine after breast cancer surgery with axillary nodes dissection

<p>Abstract</p> <p>Background</p> <p>The effect of local infiltration after breast surgery is controversial. This prospective double blind randomized study sought to document the analgesic effect of local anaesthetic infiltration after breast cancer surgery.</p> <p>Methods</p> <p>Patients scheduled for mastectomy or tumorectomy and axillary nodes dissection had immediate postoperative infiltration of the surgical wound with 20 ml of ropivacaine 7.5 mg.ml^-1or isotonic saline. Pain was assessed on a visual analogue scale at H2, H4, H6, H12, H24, H72, and at 2 month, at rest and on mobilization of the arm. Patient'comfort was evaluated with numerical 0-3 scales for fatigue, quality of sleep, state of mood, social function and activity.</p> <p>Results</p> <p>Twenty-two and 24 patients were included in the ropivacaine and saline groups respectively. Postoperative pain was lower at rest and on mobilization at 2, 4 and 6 hour after surgery in the ropivacaine group. No other difference in pain intensity and patient 'comfort scoring was documented during the first 3 postoperative days. Patients did not differ at 2 month for pain and comfort scores.</p> <p>Conclusion</p> <p>Single shot infiltration with ropivacaine transiently improves postoperative pain control after breast cancer surgery.</p> <p>Trial registration number</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01404377">NCT01404377</a></p

The immunobiology of the mammalian epididymis: the black box is now open!

International audienceSpermatozoa represent an immunologic challenge for the mammalian males. They are produced long after the establishment of the immune library of the individual and harbor specific spermatic antigens that are found nowhere else in other organs, tissues and cells. Consequently, spermatozoa are somehow "foreign" to the male adaptive immune system. In order not to elicit autoimmune responses that would be detrimental for male fertility, spermatozoa should be either physically separated from the adaptive immune response and/or, the immune system challenged by spermatic antigens must be efficiently silenced. Within the mammalian male genital tract it becomes more and more obvious that a range of strategies are at stake to ensure that the immune-stranger spermatozoa do not constitute an immunological issue. In this review the focus will be on the immune status of the epididymis tubule, in which spermatozoa that have left the testes will mature for approximately 2 weeks and may be stored for prolonged period of time. How the epididymal immune environment compares to that of the testis and what are the immune regulatory processes at work in the epididymal compartment will only be briefly described. Instead, this review will focus on recent data that highlight epididymal immune regulatory actors that partly explain/illustrate the rather complicated, fragile but nevertheless robust immune environment of the epididymis

Identification of Arvicola terrestris scherman Sperm Antigens for Immune Contraceptive Purposes

International audienceThe cyclical proliferation of the wild fossorial rodent Arvicola terrestris scherman (ATS) is critical in mid-mountain ecosystems of several European countries. Our goal is to develop an immunocontraceptive vaccine to control their fertility, as a sustainable alternative to chemical poisons currently used. Indeed, these chemicals cause the death of ATS predators and animals sharing their ecosystem, and current laws progressively limit their use, making the development of a targeted vaccination strategy an interesting and efficient alternative. In order to identify species-specific sperm antigens, male and female ATS received subcutaneous injections of whole ATS spermatozoa to elicit an immune response. The analysis of the immune sera led to the identification of 120 immunogenic proteins of sperm cells. Of these, 15 were strictly sperm-specific and located in different regions of the male gamete. Some of these antigens are proteins involved in molecular events essential to the reproductive process, such as sperm-egg interaction, acrosomal reaction, or sperm motility. This approach not only identified a panel of immunogenic proteins from ATS sperm cells, but also demonstrated that some of these proteins trigger an immune response in both male and female ATS. These spermatic antigens are good candidates for the development of a contraceptive vaccine

Ecological Monitoring and Management App (EMMA) for Older Adults With Chronic Pain: Protocol for a Design and Feasibility Study

Background: Chronic pain is a complex problem for many older adults that affects both physical functioning and psychological well-being. Mobile health (mHealth) technologies have shown promise in supporting older persons in managing chronic conditions. Cognitive behavior therapy (CBT) is recommended for older people with chronic pain. However, online treatment programs for chronic pain are not aimed at the needs of older people and offer standard therapies without providing tailored treatment for this population. To address this problem, we will develop a psychological internet-based intervention based on ecological monitoring of daily life experiences with chronic pain, called EMMA to support self-management of chronic pain in older adults. Method: The key clinical and engagement features of the intervention were established through the integration of evidence-based material from cognitive behavioral therapy for the treatment of chronic pain in older adults. The development process uses a CoDesign approach and actively involves the end- users in the design process by incorporating feedback from focus groups with older adults in order to inform a user centered intervention design. For the CoDesign process, we will include 10 older adults with chronic pain that will discuss the requirements in workshops in order to ensure suitability for older adults with chronic pain. In order to test the feasibility and acceptability of the intervention, we will include a sample of 30 older adults with chronic pain that will test all features of the intervention for a period of eight consecutive weeks. After the trial period, validated instruments to assess usability and acceptability, as well as influence on pain levels and associated physical and psychological symptoms will be filled out by the participants. Participants will be invited to take part in a semi-structured telephone interview after the trial period to explore their experiences using the app. Results: Required changes to assure usability and acceptability will afterwards directly implemented in the application. The digitalization of the pain diary and psychotherapeutic content has started. Recruitment of participants for the co-design workshops will start as soon as we have a functioning prototype of the electronic pain diary and EMMA intervention which is to be expected in September 2021. The feasibility study will start as soon as the co-design process is finished and all required changes implemented into the pain diary and the EMMA intervention. We expect to start the feasibility study at the beginning of 2022

An Ecological Monitoring and Management App (EMMA) for Older Adults With Chronic Pain: Protocol for a Design and Feasibility Study

Background: Chronic pain is a complex problem for many older adults that affects both physical functioning and psychological well-being. Mobile health (mHealth) technologies have shown promise in supporting older persons in managing chronic conditions. Cognitive behavior therapy is recommended for older people with chronic pain. However, web-based treatment programs for chronic pain are not aimed at the needs of older people and offer standard therapies without providing tailored treatment for this population. Objective: To address this problem, we aim to develop a psychological web-based intervention for ecological monitoring of daily life experiences with chronic pain called EMMA to support self-management of chronic pain in older adults. Methods: The key clinical and engagement features of the intervention were established through the integration of evidence-based material from cognitive behavioral therapy for the treatment of chronic pain in older adults. The development process uses a co-design approach and actively involves end-users in the design process by incorporating feedback from focus groups with older adults in order to inform a user-centered intervention design. For the co-design process, we will include 10 older adults with chronic pain, who will discuss the requirements for the app in workshops in order to ensure suitability of the app for older adults with chronic pain. In order to test the feasibility and acceptability of the intervention, we will include a sample of 30 older adults with chronic pain who will test all features of the intervention for a period of 8 consecutive weeks. After the trial period, validated instruments will be used to assess usability and acceptability, as well as influence on pain levels and associated physical and psychological symptoms. Participants will be invited to take part in a semistructured telephone interviews after the trial period to explore their experiences using the app. Results: Digitalization of the pain diary and psychotherapeutic content has started. Recruitment of participants for the co-design workshops will start as soon as we have a functioning prototype of the electronic pain diary and EMMA intervention, which is expected to be in September 2021. The feasibility study will start as soon as the co-design process is finished and required changes have been implemented into the pain diary and the EMMA intervention. We expect to start the feasibility study early in 2022. Conclusions: Required changes to assure usability and acceptability will be directly implemented in the app. EMMA brings together a strong body of evidence using cognitive behavioral and self-management theory with contemporary mHealth principles, allowing for a cost-effective intervention that can be used to target chronic pain anywhere and anytime by older adults. Given the ubiquity of mHealth interventions for chronic conditions, the results of this study may serve to inform the development of tailored self-management interventions

GPX5, the selenium-independent glutathione peroxidase-encoding single copy gene is differentially expressed in mouse epididymis

International audienc

Phénotypage des animaux modèles : L'invalidation du gène hspb1 pour comprendre les mécanismes de tendreté de la viande bovine

La qualité sensorielle de la viande bovine est un critère important d’appréciation par lesconsommateurs qui demeurent insatisfaits en particulier de la tendreté. Celle-ci a une origine complexeet multifactorielle, qui la rend difficilement maîtrisable par la filière bovine. À l’issue de plusieurs annéesde recherche, notre équipe a établi une liste de marqueurs de la tendreté de la viande. Dans cetteliste, les Heat Shock Proteins (Hsp) figurent à des « carrefours » biologiques dans l’interactomemusculaire lié à la tendreté. Parmi elles, la Hsp27 est différentiellement exprimée entre des musclesde tendreté extrême. Comprendre le rôle de Hsp27 et de ses interacteurs dans l’établissement de latendreté est un des enjeux des recherches en production de viande.Afin d’atteindre cet objectif, l’invalidation du gène hspb1 (codant la protéine Hsp27) a été réalisée parrecombinaison homologue (KO) chez la souris (en collaboration avec l'IGFL et le PBES Lyon). Cemodèle a permis d’analyser les conséquences de l’invalidation de hspb1 sur le développement et lescaractéristiques des tissus liés à la qualité (muscle et tissus adipeux), ainsi que sur la fonctionnalité del’interactome "tendreté". Ce travail s’insérait dans l’Action Incitative du Département Phase« Phénotypage des animaux modèles » (2009-2012).Les souris KO hspb1-/- sont viables et fertiles, ne présentent aucune anomalie apparente mais ont unformat plus petit que celui de leurs témoins (Kammoun et al, 2013a). Au niveau plasmatique, uneinteraction génotype x âge x sexe a été révélée pour 16 paramètres biologiques sur les 36 indicateursmétaboliques mesurés. Les principales différences détectées entre KO et témoins suggèrent desdifférences de métabolismes hépatique et lipidique chez les mâles et de métabolisme du glucose et del’acide urique chez les femelles. Aucune différence n'a été observée pour les paramètresreprésentatifs du métabolisme musculaire. La structure musculaire des animaux a été analysée defaçon complémentaire par microscopie optique et électronique à transmission. La première approche n'a pas permis de révéler de différences dans les caractéristiques des fibres musculaires (typecontractile et métabolique, forme, périmètre, surface de section) à l'exception d'une tendance pour uneproportion plus élevée de fibres de petite taille chez les souris KO. Toutefois, l'analyse des profilsélectrophorétiques des isoformes de chaînes lourdes de myosine suggèrent un retard de maturationmusculaire chez les souris KO. Au niveau ultrastructural, les fibres des animaux KO sont caractérisées,comparativement à celle des témoins, par un appareil contractile musculaire moins organisé (Figure 1)qui devient très déstructuré 72h post-mortem . Ainsi le phénotype musculaire fin des souris KO estaltéré.Une analyse bioinformatique a été réalisée dans l'objectif de compléter la liste des interacteurs de laprotéine Hsp27 et des gènes cibles de l’invalidation d’hspb1 susceptibles de participer à desdifférences de structure du muscle et de la tendreté. Les partenaires ou cibles prédits de Hsp27 sontdes protéines impliquées dans différentes fonctions, comme des Hsps (Hsp20, Cryab, Hsp70a1a etHsp90aa1), des régulateurs de l'apoptose (Fas, Chuk, et caspase-3), des facteurs de traduction(Eif4E et Eif4G1), des protéines du cytosquelette (Desmine) et des antioxydants (Sod1). Lesabondances de 15 protéines ont été quantifiées par Western blot dans deux muscles de souris KO etde leurs témoins. Elles sont modifiées chez les souris dépourvues de Hsp27 principalement dans lemuscle le plus oxydatif (Kammoun et al., 2012, 2013b). Cette étude démontre l'existence de liensfonctionnels entre Hsp27 et ses cibles prédites.L'ensemble des données issues de cette étude réalisée dans une espèce modèle apporte desconnaissances nouvelles sur les mécanismes moléculaires impliqués dans l’établissement de latendreté de la viande bovine. Elle suggère que le statut en Hsp, les processus apoptotiques et laprotection contre le stress oxydatif contribue à l'évolution de l'ultrastructure post-mortem des muscleset à la tendreté de la viande. Ces données seront complétées par les résultats d'une analyseprotéomique en cours. Ces nouvelles connaissances seront validées ultérieurement sur muscle bovin

Regulation of the Aldo-Keto Reductase Gene akr1b7 by the Nuclear Oxysterol Receptor LXRα (Liver X Receptor-α) in the Mouse Intestine: Putative Role of LXRs in Lipid Detoxification Processes

International audienc