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The emerging understanding of gut microbiota as ‘metabolic machinery’ influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to ‘healthy’ controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

PURPOSE:COVID-19 challenged medical practice and graduate medical education. Building on previous initiatives, we describe and reflect on the formative process and goals of the Hematology-Oncology Collaborative Videoconferencing Learning Initiative, a trainee-led multi-institutional virtual COVID-19 learning model.METHODS:Clinical fellows and faculty from 13 US training institutions developed consensus needs, goals, and objectives, recruited presenters, and generated a multidisciplinary COVID-19 curriculum. Weekly Zoom conferences consisted of two trainee-led instructional segments and a trainee-moderated faculty Q&A panel. Hematology-oncology training program faculty and trainees were the targeted audience. Leadership evaluations consisted of anonymized baseline and concluding mixed methods surveys. Presenter evaluations consisted of session debriefs and two structured focus groups. Conference evaluations consisted of attendance, demographics, and pre- or postmultiple-choice questions on topic learning objectives.RESULTS:In 6 weeks, the initiative produced five conferences: antivirals, anticoagulation, pulmonology, provider resilience, and resource scarcity ethics. The average attendance was 100 (range 57-185). Among attendees providing both pre- and postconference data, group-level knowledge appeared to increase: antiviral (n = 46) pre-/postcorrect 82.6%/97.8% and incorrect 10.9%/2.2%, anticoagulation (n = 60) pre-/postcorrect 75%/93.3% and incorrect 15%/6.7%, and pulmonary (n = 21) pre-/postcorrect 66.7%/95.2% and incorrect 33.3%/4.8%. Although pulmonary management comfort appeared to increase, comfort managing of antivirals and anticoagulation was unchanged. At the conclusion of the pilot, leadership trainees reported improved self-confidence organizing multi-institutional collaborations, median (interquartile range) 58.5 (50-64) compared with baseline 34 (26-39), but did not report improved confidence in other educational or leadership skills.CONCLUSION:During crisis, trainees built a multi-institutional virtual education platform for the purposes of sharing pandemic experiences and knowledge. Accomplishment of initiative goals was mixed. Lessons learned from the process and goals may improve future disaster educational initiatives.

μ-Crystallin, encoded by the CRYM gene, binds the thyroid hormones, T3 and T4. Because T3 and T4 are potent regulators of metabolism and gene expression, and CRYM levels in human skeletal muscle can vary widely, we investigated the effects of overexpression of Crym. We generated transgenic mice, Crym tg, that expressed Crym protein specifically in skeletal muscle at levels 2.6–147.5 fold higher than in controls. Muscular functions, Ca2+ transients, contractile force, fatigue, running on treadmills or wheels, were not significantly altered, although T3 levels in tibialis anterior (TA) muscle were elevated ~190-fold and serum T4 was decreased 1.2-fold. Serum T3 and thyroid stimulating hormone (TSH) levels were unaffected. Crym transgenic mice studied in metabolic chambers showed a significant decrease in the respiratory exchange ratio (RER) corresponding to a 13.7% increase in fat utilization as an energy source compared to controls. Female but not male Crym tg mice gained weight more rapidly than controls when fed high fat or high simple carbohydrate diets. Although labeling for myosin heavy chains showed no fiber type differences in TA or soleus muscles, application of machine learning algorithms revealed small but significant morphological differences between Crym tg and control soleus fibers. RNA-seq and gene ontology enrichment analysis showed a significant shift towards genes associated with slower muscle function and its metabolic correlate, β-oxidation. Protein expression showed a similar shift, though with little overlap. Our study shows that μ-crystallin plays an important role in determining substrate utilization in mammalian muscle and that high levels of μ-crystallin are associated with a shift toward greater fat metabolism., Graphical abstract Image, Highlights • μ-Crystallin (Crym) is expressed specifically in transgenic skeletal muscle at highly elevated levels. • T3 is increased ~190 fold in the Tibialis anterior muscle of Crym tg mice. • Small but significant changes in gene and protein expression in tg muscle towards a slow twitch, oxidative phenotype. • Metabolic studies show that Crym tg mice increase their use of fat as an energy source. • Female Crym tg mice gain weight faster on high fat or simple carbohydrate diets than controls.

BACKGROUND Despite high rates of alcohol abstinence, Alaska Native and American Indian (ANAI) people experience a disproportionate burden of alcohol-related morbidity and mortality. Lack of culturally relevant resources, combined with limited treatment access and privacy concerns regarding peer-support programs in rural areas, poses particular treatment barriers for ANAI people. OBJECTIVE Objective: This study was the first phase of a feasibility study of a culturally tailored version of an off-the-shelf smartphone app to aid ANAI people in managing or reducing their use of alcohol. Its goal was to gather insights and preferences from ANAI people and ANAI-serving healthcare providers to guide feature development and cultural adaptation. METHODS In October 2018 – September 2019, we conducted semi-structured interviews with 24 ANAI patients and 8 providers in a Tribal healthcare organization in southcentral Alaska. RESULTS Participants generally endorsed the usefulness of a smartphone app for alcohol self-management, citing anonymity, 24/7 access, peer support, and patient choice as key attributes. Desired cultural adaptations included ANAI and land-themed design elements, cultural content (e.g., stories from Elders), and spiritual resources. CONCLUSIONS ANAI patients and their providers were receptive to the idea of a culturally adapted smartphone app for sobriety support. They considered an app especially useful for rural-dwelling ANAI people, as well as those who lack timely access to treatment services or prefer to work toward managing their alcohol use outside the clinical setting. These results are guiding the next phase of the study.

In recent years, the aviation industry has taken a leading role in the integration of composite structures to develop lighter and more fuel efficient aircraft. Among the leading concepts to achieve this goal is the Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) concept. The focus of most PRSEUS studies has been on developing an hybrid wing body structure, with only a few discussing the application of PRSEUS to a tube-wing fuselage structure. Additionally, the majority of investigations for PRSEUS have focused on experimental validation of anticipated benefits rather than developing a methodology to capture the behavior of stitched structure analytically. This paper presents an overview of a numerical methodology capable of accurately describing PRSEUS’ construction and how it may be implemented in a barrel fuselage platform resorting to high-fidelity mesoscale modeling techniques. The methodology benefits from fresh user defined strategies developed in a commercially available finite element analysis environment. It further proposes a new approach for improving the ability to predict deformation in stitched composites, allowing for a better understanding of the intricate behavior and subtleties of stitched aerospace structures.

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Brain metastases account for the majority of malignant brain tumors and as newer cancer treatments improve patient survival, the reported incidence of brain metastases is increasing. Lung cancer is the most frequent origin of metastases to the brain, and this diagnosis is associated with significant morbidity as well as decreased quality of life and a worse prognosis. The treatment for brain metastases in NSCLC has historically been local therapy, either surgery or radiation, as many chemotherapies have limited efficacy in the brain. These strategies are highly effective but can be a source of morbidity themselves. Newer systemic therapies, including targeted small molecule drugs and immunotherapy, have shown promise in treating NSCLC associated CNS disease either alone or in combination with local therapies. Increasing evidence for this strategy is accumulating as more clinical trials allow the inclusion of patients with untreated asymptomatic brain metastases. This chapter summarizes the current use of systemic therapy in the treatment of brain metastases in NSCLC.

INTRODUCTION Dysferlin-deficient murine muscle sustains severe damage after repeated eccentric contractions. METHODS With a robotic dynamometer, we studied the response of dysferlin-sufficient and dysferlin-deficient mice to 12 weeks of concentrically or eccentrically biased contractions. We also studied whether concentric contractions before or after eccentric contractions reduced muscle damage in dysferlin-deficient mice. RESULTS After 12 weeks of concentric training, there was no net gain in contractile force in dysferlin-sufficient or dysferlin-deficient mice, whereas eccentric training produced a net gain in force in both mouse strains. However, eccentric training induced more muscle damage in dysferlin-deficient vs dysferlin-sufficient mice. Although concentric training produced minimal muscle damage in dysferlin-deficient mice, it still led to a prominent increase in centrally nucleated fibers. Previous exposure to concentric contractions conferred slight protection on dysferlin-deficient muscle against damage from subsequent injurious eccentric contractions. DISCUSSION Concentric contractions may help dysferlin-deficient muscle derive the benefits of exercise without inducing damage.

Resume Objectifs Ce travail vise a argumenter l’hypothese psychosomatique de l’etiologie des vulvodynies spontanees et d’en deduire des axes therapeutiques adaptes. Methodologie Les donnees de ce travail sont essentiellement issues de l’experience clinique des auteurs, notamment dans le cadre d’une consultation multidisciplinaire de pathologie vulvaire. Les hypotheses emises sont confirmees par des travaux scientifiques cites en reference. Discussion La definition de la vulvodynie ne semble plus aujourd’hui remise en question. Il s’agit cependant d’un ensemble de situations assez heteroclites, parmi lesquelles les vulvodynies generalisees spontanees (GVD) posent incontestablement le plus de problemes diagnostiques et therapeutiques. Diverses explications physiopathologiques ont ete avancees. De nombreux arguments permettent aux auteurs de ce travail de penser que l’hypothese psychosomatique doit etre privilegiee. Pour apparaitre, la GVD y suppose la conjonction de 3 parametres : d’une part, une personnalite dominee par l’anxiete, voire la depression, d’autre part, un facteur declenchant, local ou psychologique, et enfin une problematique sexologique sous-jacente. Cette symptomatologie altere toujours de maniere importante la qualite de vie de la patiente et genere a son tour une angoisse considerable, a fortiori dans la mesure ou la plupart des praticiens ne la connaissent pas bien, et ne peuvent ni l’expliquer, ni proposer un traitement logique et efficace. Aucune approche therapeutique simple n’a fait la preuve de son efficacite et, pour les auteurs, ne pourra jamais le faire. Cette approche therapeutique est necessairement complexe, multidisciplinaire, et fait notamment appel a une prise en charge psychosexologique qui integrera un travail sur le corps. Conclusion La GVD ne doit plus rester une symptomatologie mysterieuse qui altere de maniere majeure la qualite de vie de la patiente et interpelle le corps medical. Cependant, il s’agit d’une maladie complexe, dont la prise en charge est multidisciplinaire, chronophage, et qui doit prendre en consideration une dimension psychosexologique determinante.

Ibuprofen, a nonsteroidal anti-inflammatory drug, and nitric oxide (NO) donors have been reported to reduce the severity of muscular dystrophies in mice associated with the absence of dystrophin or α-sarcoglycan, but their effects on mice that are dystrophic due to the absence of dysferlin have not been examined. We have tested ibuprofen, as well as isosorbide dinitrate (ISDN), a NO donor, to learn whether used alone or together they protect dysferlin-null muscle in A/J mice from large strain injury (LSI) induced by a series of high strain lengthening contractions. Mice were maintained on chow containing ibuprofen and ISDN for 4 weeks. They were then subjected to LSI and maintained on the drugs for 3 additional days. We measured loss of torque immediately following injury and at day 3 postinjury, fiber necrosis, and macrophage infiltration at day 3 postinjury, and serum levels of the drugs at the time of euthanasia. Loss of torque immediately after injury was not altered by the drugs. However, the torque on day 3 postinjury significantly decreased as a function of ibuprofen concentration in the serum (range, 0.67-8.2 µg/ml), independent of ISDN. The effects of ISDN on torque loss at day 3 postinjury were not significant. In long-term studies of dysferlinopathic BlAJ mice, lower doses of ibuprofen had no effects on muscle morphology, but reduced treadmill running by 40%. Our results indicate that ibuprofen can have deleterious effects on dysferlin-null muscle and suggest that its use at pharmacological doses should be avoided by individuals with dysferlinopathies.

B6.A-Dysfprmd /GeneJ (BLAJ) mice model human limb-girdle muscular dystrophy 2B (LGMD2B), which is linked to mutations in the dysferlin (DYSF) gene. We tested the hypothesis that, the calcium ion (Ca2+ ) channel blocker diltiazem (DTZ), reduces contraction-induced skeletal muscle damage, in BLAJ mice. We randomly assigned mice (N = 12; 3-4 month old males) to one of two groups - DTZ (N = 6) or vehicle (VEH, distilled water, N = 6). We conditioned mice with either DTZ or VEH for 1 week, after which, their tibialis anterior (TA) muscles were tested for contractile torque and susceptibility to injury from forced eccentric contractions. We continued dosing with DTZ or VEH for 3 days following eccentric contractions, and then studied torque recovery and muscle damage. We analyzed contractile torque before eccentric contractions, immediately after eccentric contractions, and at 3 days after eccentric contractions; and counted damaged fibers in the injured and uninjured TA muscles. We found that DTZ improved contractile torque before and immediately after forced eccentric contractions, but did not reduce delayed-onset muscle damage that was observed at 3 days after eccentric contractions.

Resume Objectifs Ce travail vise a relancer le debat quelque peu abandonne sur certains questionnements ethiques qui concernent la sexologie et les sexologues en France. Methodologie Les donnees de ce travail sont essentiellement issues des 35 annees d’exercice de la sexologie de l’auteur, et des 20 annees d’enseignement de la discipline ; quelques references bibliographiques illustrent certains des themes abordes. Discussion Si, en theorie, il reste souvent delicat de distinguer l’ethique de la morale, en pratique c’est a propos de ce qui devrait etre la norme que l’avis du sexologue est souvent sollicite. Mais est-il possible d’envisager que des normes sexuelles puissent un jour etre etablies ? Est-ce le role du sexologue de les edicter ? Est-il possible de preciser un cadre ethique pour l’exercice de la sexologie ? Est-il utile de demander aux soignants de s’engager par une adhesion a un code d’ethique ? Quels outils est-il indispensable de leur fournir pour echapper a certains pieges de la relation therapeutique, et de ses consequences ethiquement injustifiables ? Echapper aux risques nes d’un usage abusif du savoir ou du pouvoir sur le patient ? N’est-il pas urgent que l’enseignement donne au corps medical integre enfin concretement les notions elementaires a connaitre pour assurer la prise en charge des problematiques sexuelles les plus frequentes ? Aucune de ces questions ne peut evidemment esperer une reponse simple et rapide, mais les elements avances de ce travail esperent alimenter la reflexion a leur propos. Conclusion Selon l’auteur, la mise au devant de la scene des questionnements ethiques sur la sexologie est indispensable, d’une part, pour aider les sexologues dans leur exercice, d’autre part, asseoir la credibilite de cette discipline et esperer dans les annees a venir une veritable reconnaissance.

Resume Introduction L’industrie pornographique est omnipresente chez les adolescents qui sont pratiquement tous exposes via Internet, volontairement ou non, et a un âge plus ou moins precoce. Existe-t-il un lien entre l’exposition a la pornographie et certaines conduites a risque ? Methode Huit cent douze etudiants lillois ont repondu anonymement a un questionnaire propose a l’occasion d’une consultation en centre de sante. L’analyse statistique a ete menee a l’aide de regressions logistiques et lineaires. Resultats L’exposition a la pornographie concerne pratiquement tous les hommes et 80 % des femmes. L’âge moyen de la premiere exposition est de 15,2 ans. La precocite d’exposition est liee a une activite sexuelle plus precoce, a une recherche de partenaires occasionnel(le)s plus frequente et a une consommation de cannabis plus frequente. L’âge d’exposition ne semble pas en revanche influencer le nombre de partenaires sexuel(le)s, le fait de pratiquer la penetration anale, la consommation d’alcool ou de tabac, l’utilisation de contraceptifs et la prise de risque vis-a-vis des infections sexuellement transmissibles. Le fait de regarder frequemment des images pornographiques est lie a une activite sexuelle plus precoce, a un plus grand nombre de partenaires sexuel(le)s, au fait de rechercher des partenaires occasionnel(le)s, a une pratique de la penetration anale, a une moindre prevention des infections sexuellement transmissibles et des grossesses non desirees et enfin a une augmentation des consommations d’alcool et de cannabis. En conclusion, ces resultats doivent interpeller et amener tous les acteurs de sante sexuelle et d’education a la sexualite a renforcer l’information donnee aux adolescents.

Summary Introduction The pornography industry is a pervasive influence on adolescents, nearly all of whom are exposed to it via the internet, either willingly or unwillingly and at a more or less premature age. Is there an association between exposure to pornography and some forms of risk behaviour? Method Eight hundred and twelve Lille students responded anonymously to a questionnaire given to them on the occasion of a consultation at a health centre. Logistic and linear regressions were used for statistical analysis. Findings Nearly all men and 80% of women had been exposed to pornography. The average age of initial exposure was 15.2 years. Exposure at a premature age is associated with sexual activity at a younger age and with a greater inclination to seek out casual partners and use cannabis more frequently. The age of exposure does not on the other hand appear to have any influence on the number of sexual partners, the practice of anal penetration, alcohol or tobacco consumption, contraceptive use and taking risks in terms of sexually transmitted infections. Frequent viewing of pornographic images is associated with sexual activity at a younger age, a larger number of sexual partners, an inclination to seek out casual partners, the practice of anal penetration, a lower level of prevention of sexually transmitted infections and unwanted pregnancies and finally, a higher consumption of alcohol and cannabis. In conclusion, these findings should be taken into account, and should lead those involved in sexual health and sex education to increase the amount of information they provide to adolescents.