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Oligodendrocytes are the myelin-forming cells of the vertebrate CNS. Little is known about the molecular control of region-specific oligoden-drocyte development. Here, we show that oligodendrogenesis in the mouse rostral hindbrain, which is organized in a metameric series of rhombomere-derived (rd) territories, follows a rhombomere-specific pattern, with extensive production of oligodendrocytes in the pontine territory (r4d) and delayed and reduced oligodendrocyte production in the prepontine region (r2d, r3d). We demonstrate that segmental organization of oligodendrocytes is controlled by Hox genes, namely Hoxa2 and Hoxb2. Specifically, Hoxa2 loss of function induced a dorsoven-tral enlargement of the Olig2/Nkx2.2-expressmg oligodendrocyte progenitor domain, whereas conditional Hoxa2 overexpression in the 0!ig2 domain inhibited oligodendrogenesis throughout the brain. In contrast, Hoxb2 deletion resulted in a reduction of the pontine oligodendrogenic domain. Compound Hoxa2-/-IHoxb2-/- mutant mice displayed the phenotype of Hoxb2-/- mutants in territories coexpressing Hoxa2 and Hoxb2 (rd3, rd4), indicating that Hoxb2 antagonizes Hoxa2 during rostral hindbrain oligodendrogenesis. This study provides the first in vivo evidence that Hox genes determine oligodendrocyte regional identity in the mammalian brain. [ABSTRACT FROM AUTHOR]

Perlecan (HSPG2), a basement membrane-type heparan sulfate proteoglycan, has been implicated in the development of aortic tissue. However, its role in the development and maintenance of the aortic wall remains unknown. Perlecan-deficient mice (Hspg2−/−-Tg: Perl KO) have been found to show a high frequency (15–35%) of aortic dissection (AD). Herein, an analysis of the aortic wall of Perl KO mice revealed that perlecan deficiency caused thinner and partially torn elastic lamina. Compared to the control aortic tissue, perlecan-deficient aortic tissue showed a significant decrease in desmosine content and an increase in soluble tropoelastin levels, implying the presence of immature elastic fibers in Perl KO mice. Furthermore, the reduced expression of the smooth muscle cell contractile proteins actin and myosin in perlecan-deficient aortic tissue may explain the risk of AD. This study showed that a deficiency in perlecan, which is localized along the elastic lamina and at the interface between elastin and fibrillin-1, increased the risk of AD, largely due to the immaturity of extracellular matrix in the aortic tissue. Overall, we proposed a new model of AD that considers the deficiency of extracellular molecule perlecan as a risk factor. [ABSTRACT FROM AUTHOR]

Highlights from the article: First, because only a few patients are admitted to ICU after an out-of-hospital cardiac arrest (around 17% in a previous study).[2] Second, the determination of the origin of cardiac arrest is very difficult in the pre-hospital setting without biochemical and imaging parameters. We agree that according to our results, the origin of cardiac arrest cannot be considered a prognostic factor in the entire cardiac arrest population. 3 J. Engdahl, A. Bång, B.W. Karlson, J. Lindqvist, J. Herlitz, Characteristics and outcome among patients suffering from out of hospital cardiac arrest of non-cardiac aetiology, Resuscitation, 57, 2003, 33-41.

Bisphenol A (BPA) and its main substitute, bisphenol S (BPS), are synthetic organic compounds found in various consumer products, in particular food and beverage containers. Numerous reports have shown a link between bisphenol exposure, human contamination and increased health problems. BPA, BPS and their metabolites are detectable in bodily fluids (blood, urine) and were reported to affect immune cells and their responses. Though, the impact of those chemicals on neutrophils, the most abundant leukocytes in the circulation, remains poorly described. Therefore, we examined the effects of BPA, BPS and their monoglucuronide conjugates on neutrophil energy metabolism and anti-microbial functions, mainly phagocytosis, superoxide anion generation and CXCL8/IL-8 chemokine production. We observed that short and prolonged exposures of neutrophils to these chemicals modulate the basal and the bacterium-derived peptide N-formyl-methionyl-leucyl-phenylalanine-induced glycolysis, with BPS causing the most alterations. The variation in energy metabolism was not associated with dysfunctions in cell cytotoxicity, phagocytosis, nor superoxide anion production upon exposure to bisphenols. In contrast, bisphenols significantly reduced the production of CXCL8/IL-8 by neutrophils, an effect found to be greater with the glucuronidated metabolites. Our study highlights that BPA, BPS and their glucuronidated metabolites alter the energy metabolism and certain anti-microbial responses of neutrophils, with possible health implications. Importantly, we found that BPS and the glucuronidated metabolites of BPA and BPS showed higher endocrine-disrupting potential than BPA. More studies on bisphenols, especially the less-documented BPS and bisphenol metabolites, are needed to fully determine their risks, allow better regulation of these compounds, and restrict their extensive usage. [Display omitted] • Bisphenols modulate neutrophil basal and fMLP-induced glycolysis. • Bisphenols do not affect neutrophil viability nor phagocytosis. • Bisphenols reduce the production of CXCL8/IL-8 chemokine in a non-monotonic way. • BPS and glucuronidated metabolites showed the highest endocrine-disrupting potential. [ABSTRACT FROM AUTHOR]

L'évolution des technologies de santé connectée dans la prise en charge du surpoids et de l'obésité nécessite de mieux connaître les raisons pour lesquelles certains patients adhèrent et d'autre pas. Les objectifs de cette revue des revues systématiques sont d'examiner comment l'adhésion aux interventions de santé connectée dans la gestion du poids est conceptualisée et d'identifier les facteurs qui influencent l'adhésion et comment ils l'influencent. Sept revues systématiques publiées entre 2010 et 2022 ont été incluses. Les définitions et les mesures de l'adhésion ainsi que les conceptions de l'intervention sont très hétérogènes dans la littérature existante, ce qui rend difficiles les conclusions sur les réels niveaux d'adhésion. Quatre composantes ont été identifiées comme favorisant l'adhésion aux interventions de gestion de poids auprès de patients en situation de surpoids ou d'obésité : (1) l'auto-surveillance dont la facilité et la rapidité d'emploi lui confèrent un bon niveau d'adhésion ; (2) l'entretien motivationnel avec une relation soignant-patient via la vidéo ou le téléphone qui favorise l'adhésion ; (3) la thérapie comportementale demandant surtout des échanges fréquents, au mieux hebdomadaires ; (4) et la personnalisation qui doit être effective tout au long de l'intervention pour rester pertinente au regard des objectifs du patient. Cependant, la complexité des phénomènes impliqués dans l'obésité impose une analyse plus fine de l'adhésion qui ne se focalise pas simplement sur l'outil, mais qui importe également de prendre en considération leurs appropriations dans des contextes variés et donc de l'étudier du point de vue des utilisateurs. The evolution of eHealth technologies in the management of overweight and obesity requires a better understanding of the reasons why some patients are engaged, and others are not. The objectives of this review of systematic reviews are to examine how adherence to eHealth interventions in weight management is conceptualized, to identify which factors influence adherence, and how they influence it. Seven systematic reviews published between 2010 and 2022 were included. Definitions, measures of adherence and intervention designs are highly heterogeneous in the existing literature, making it difficult to draw conclusions about actual adherence levels. Four designs have been identified as promoting adherence to weight management interventions with adult patients who are overweight or obese: (1) self-monitoring which ease and speed of use give a good level of adherence; (2) motivational interviewing with a caregiver-patient relationship via video or phone that promotes adherence; (3) behavioral therapy requiring especially frequent exchanges at best weekly; (4) and personalization that must be effective throughout the intervention to remain relevant to the patient's goals. However, the complexity of the phenomena involved in obesity requires a more detailed analysis of adherence that does not only focus on the tool, but also considers the point of view of the users and their appropriation in various contexts. [ABSTRACT FROM AUTHOR]

Background Aim Study design Results Conclusion Relevance to Clinical Practice Most children admitted to a paediatric intensive care unit (PICU) now survive because of improvements in care. Many studies have identified the psychological, functional, cognitive and social impact of PICU admission on a child and their family. However, expert recommendations on follow‐up are lacking.To identify the strategies of clinical follow‐up after PICU discharge performed from 2001 to 2021.This scoping review was undertaken between January and April 2021 using three databases: PubMed, EMBASE and CINAHL. The search strategy consisted of a combination of keywords, including PICU, post‐PICU discharge and follow‐up in articles published between 2001 and 2021. The results are reported according to PRISMA‐ScR guidelines.Six‐hundred and fifty‐two articles were identified and 68 were analysed. Median age was 4.5 years and the two main reasons for PICU admission were cardiorespiratory failure and sepsis. Median length of PICU stay was 8 days. Most follow‐up was carried out by research units (88%), while 6% of studies reported follow‐up by a multidisciplinary PICU team. The most common follow‐up schedule included an assessment at PICU discharge, and then at 3, 6 and 12 months. Follow‐up for >1 year was reported in 20% of studies. One third of studies focused on follow‐up quality of life and neurological outcomes. Parental emotional impact was assessed in 7% of studies.Follow‐up after PICU discharge was highly heterogeneous regarding timing, health care professionals involved and assessment methods. There is an urgent need for standardization and coordination of PICU follow‐up because of the increasing number of patients impacted by a PICU stay.Although most patients admitted to a paediatric intensive care unit (PICU) now survive; they may develop paediatric post‐intensive care syndrome (PICS‐P). To our knowledge, there are currently no clinical guidelines regarding follow‐up after PICU discharge. This review summarizes current approaches to follow‐up after PICU discharge, including how it is carried out, who is involved and what the main aims of assessment are. [ABSTRACT FROM AUTHOR]

Background: The term dermatoporosis (DP) is used to describe the clinical signs and functional consequences of age‐related extreme skin fragility. It is associated with potentially severe complications, including deep dissecting hematomas and extended skin lacerations. No studies have evaluated the prevalence and risk factors of DP in adults aged 75 and older. Methods: The aim of our study was to assess the prevalence, complications, and risk factors of DP in a cohort of older patients hospitalized in a rehabilitation center. A case–control, single‐center study was conducted between September and October 2020 in our rehabilitation ward, Rothschild Hospital, Paris, France. A senior dermatologist and a resident in geriatric medicine performed a systematic dermatological examination. The presence of DP, its stage, its location, and complications were collected, as were demographical data, comorbidities, past sun exposure, skin phototype, treatments, and biological data. Results: A total of 101 patients (62 women, median age 86 years [extreme values 75–104]) were included. The overall prevalence of DP was 27%. Stage 1 was the most frequent. DP was mainly located on the upper limbs. Ten (37%) patients had a DP complication: eight (30%) skin lacerations and two (7%) deep dissecting hematomas. Multivariate analysis revealed a significant association between DP and age (odds ratio [OR] 5.82, 95% confidence interval [CI] 1.67–24.92, p = 0.009), smoking (OR 8.67, 95% CI 2.59–34.85, p = 0.001), recreational sun exposure (OR 4.23, 95% CI 1.30–15.21, p = 0.02), and anticoagulant therapy (OR 4.53, 95% CI 1.32–17.26, p = 0.02). Conclusion: Our study is the first to analyze the prevalence and risk factors of DP in older adults in rehabilitation. Frequency of DP makes it relevant for the geriatrician and should be described more to prevent potential severe complications. A multicentric study, with inpatients and outpatients, could evaluate the prevalence of DP in a more representative older adult population. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is the most frequent hereditary systemic autoinflammatory syndrome. FMF is usually caused by biallelic mutations in the MEFV gene, encoding Pyrin. Conclusive genetic evidence lacks for about 30% of patients diagnosed with clinical FMF. Pyrin is an inflammasome sensor maintained inactive by two kinases (PKN1/2). The consequences of MEFV mutations on inflammasome activation are still poorly understood. Here, we demonstrate that PKC superfamily inhibitors trigger inflammasome activation in monocytes from FMF patients while they trigger a delayed apoptosis in monocytes from healthy donors. The expression of the pathogenic p.M694V MEFV allele is necessary and sufficient for PKC inhibitors (or mutations precluding Pyrin phosphorylation) to trigger caspase‐1‐ and gasdermin D‐mediated pyroptosis. In line with colchicine efficacy in patients, colchicine fully blocks this response in FMF patients' monocytes. These results indicate that Pyrin inflammasome activation is solely controlled by Pyrin (de)phosphorylation in FMF patients while a second control mechanism restricts its activation in healthy donors/non‐FMF patients. This study paves the way toward a functional characterization of MEFV variants and a functional test to diagnose FMF. Synopsis: Familial Mediterranean fever (FMF) is a systemic auto‐inflammatory disease associated with MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor. The link between MEFV mutations and the dysregulated activation of the Pyrin inflammasome observed in FMF patients is unclear. Pyrin dephosphorylation is insufficient to trigger full inflammasome activation in healthy donors'monocytes while it is sufficient in FMF patients monocytes.The pathogenic MEFV mutation most frequently observed in FMF patients triggers constitutive inflammasome activation only when combined to a phosphonull MEFV mutation.UCN‐01‐induced dephosphorylation of Pyrin triggers inflammasome activation in FMF patients' monocytes but not in monocytes from other patients paving the way to a functional diagnosis of FMF. [ABSTRACT FROM AUTHOR]

Aims Of the Study: Most interventional and observational studies include cardiac arrest from cardiac origin. However, an increasing proportion of cardiac arrest results from an extra-cardiac origin, mainly respiratory. The aim of our study was to compare the characteristics and outcome of cardiac arrest patients according to the presumed cardiac or respiratory causes.Methods: This retrospective multicenter observational study included out-of-hospital cardiac arrest patients from presumed cardiac and respiratory origin treated with therapeutic hypothermia. Demographic data (age, sex, initial rhythm as shockable or non-shockable, durations of no-flow and low-flow), clinical evolution in ICU, lactate and outcome (CPC scale at ICU discharge) were compared between patients according to the presumed cardiac or respiratory origin of the cardiac arrest.Results: Two hundred and fifty-one cardiac arrest patients were included, 156 from presumed cardiac origin (62%) and 95 from presumed respiratory origin (38%). Patients with presumed cardiac cause presented more frequently a shockable rhythm (68% vs. 5%, p < 0.001), received more defibrillations attempts (2 [1-5] vs. 0 [0-0], <0.001) and needed less adrenaline (3 mg [0-5] vs. 4 mg [2-7], p = 0.01). The arterial lactate concentration on admission was higher in patients with presumed respiratory causes (6.3 mmol/L [4.2-9.8] vs. 3.2 mmol/L [1.6-5.0], p < 0.001). The proportion of patients presenting a favorable outcome was higher in the population with presumed cardiac causes, compared to its respiratory counterpart (42% vs. 19%, p < 0.001).Conclusions: Compared to presumed cardiac origin, a worse outcome and a different mode of death are associated with the presumed respiratory origin, resulting from a greater insult preceding cardiac arrest. The presumed cause of cardiac arrest could be integrated in the multimodal prognostication process. [ABSTRACT FROM AUTHOR]

Effects of early mobilization are not well documented in patients with aneurysmal subarachnoid hemorrhage (aSAH). Only a few studies have investigated it through progressive mobilization protocols and suggested that it is safe and feasible. This study aimed to determine the impact of early out-of-bed mobilization (EOM) on 3-month functional outcome and cerebral vasospasm (CVS) occurrence in patients with aSAH. A retrospective review of consecutive patients admitted to the intensive care unit with a diagnosis of aSAH was performed. EOM was defined as out-of-bed (OOB) mobilization performed before or on day 4 after aSAH onset. The primary outcome was 3-month functional independence (i.e., a modified Rankin Scale below 3) and the occurrence of CVS. A total of 179 patients with aSAH met the inclusion criteria. Thirty-one patients constituted the EOM group, and 148 patients were in the delayed out-of-bed mobilization group. Functional independence was more frequent in the EOM group than in the delayed out-of-bed mobilization group (n = 26 [84%] vs. n = 83 [56%], P = 0.004). In a multivariable analysis, EOM was an independent predictor of functional independence (adjusted odds ratio = 3.11; 95% confidence interval, 1.11–10.36; P < 0.05). The delay between bleeding and first OOB mobilization was also identified as an independent risk factor for the occurrence of CVS (adjusted odds ratio = 1.12; 95% confidence interval = 1.06–1.18, P < 0.001). EOM was independently associated with favorable functional outcome after aSAH. The delay between bleeding and OOB mobilization was an independent risk factor for reduced functional independence and CVS occurrence. Prospective randomized trials are necessary to confirm these results and improve clinical practice. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The initial management of a trauma patient is a critical and demanding period. The use of extended focused assessment sonography for trauma (eFAST) has become more prevalent in trauma rooms, raising questions about the real 'added value' of chest X-rays (CXRs) and pelvic X-rays (PXR), particularly in haemodynamically stable trauma patients. The aim of this study was to evaluate the effectiveness of a management protocol integrating eFAST and excluding X-rays in stable trauma patients. Methods: This was a prospective, interventional, single-centre study including all primary blunt trauma patients admitted to the trauma bay with a suspicion of severe trauma. All patients underwent physical examination and eFAST (assessing abdomen, pelvis, pericardium and pleura) before a whole-body CT scan (WBCT). Patients fulfilling all stability criteria at any time in transit from the scene of the accident to the hospital were managed in the trauma bay without chest and PXR. Results: Amongst 430 patients, 148 fulfilled the stability criteria (stability criteria group) of which 122 (82 %) had no X-rays in the trauma bay. No diagnostic failure with an immediate clinical impact was identified in the stability criteria group (SC group). All cases of pneumothorax requiring chest drainage were identified by eFAST associated with a clinical examination before the WBCT scan in the SC group. The time spent in the trauma bay was significantly shorter for the SC group without X-rays compared to those who received any X-ray (25 [20; 35] vs. 38 [30; 60] min, respectively; p < 0.0001). An analysis of the cost and radiation exposure showed savings of 7000 Є and 100 mSv, respectively. Conclusions: No unrecognized diagnostic with a clinical impact due to the lack of CXR and PXR during the initial management of stable trauma patients was observed. The eFAST associated with physical examination provided the information necessary to safely complete the WBCT scan. It allowed a sensible cost and radiation saving. [ABSTRACT FROM AUTHOR]

Glycosylation is an important mechanism regulating various biological processes, including intercellular signaling and adhesion. α-1,6-fucosyltransferase (Fut8) belongs to a family of enzymes that determine the terminal structure of glycans. Fut8 is widely conserved from Caenorhabditis elegans to humans, and its mutants have been reported in humans, mice, and zebrafish. Although mutants show various symptoms, such as spinal deformity and growth retardation, its effects on skeletal muscles are unknown. We aimed to elucidate the function of Fut8 in skeletal muscle using zebrafish and C2C12 cells for evaluation. We observed that most fut8a morphants died at 2 days post-fertilization (dpf) or in earlier developmental stages even at low concentrations of morpholino oligonucleotides (MOs). Mutant juveniles also had small body sizes, and abnormal myocepta and sarcomere structures, suggesting that Fut8a plays important roles in myogenesis. Moreover, treatment of C2C12 cells with 2-fluorofucose (2FF), a fucosylation inhibitor, during cell differentiation dramatically reduced the expression of myogenic genes, such as Myomaker and other myogenic fusion genes, and inhibited myotube formation. These results indicate that Fut8 is an important factor in myogenesis, and myofusion in particular. [ABSTRACT FROM AUTHOR]

The myeloid inhibitory receptor CLEC12A negatively regulates inflammation. Reduced CLEC12A expression enhances inflammation in CLEC12A knock-out mice with collagen antibody-induced arthritis. Moreover, CLEC12A internalisation augments human neutrophil activation. We thus postulated that CLEC12A expression on circulating myeloid cells of rheumatoid arthritis patients is associated with disease manifestations. Cell-surface, CLEC12A receptor expression was determined on circulating neutrophils and monocytes of eRA patients and of healthy donors. Generalized estimating equations model, Student's t-test and Spearman's correlations were performed to compare CLEC12A expression between groups and test its association with disease activity and clinical parameters. Plasma cytokines were measured by multiplex immunoassay. Patients with reduced neutrophil or monocyte CLEC12A expression at baseline and at 3 months have an increased simple disease activity index. Low baseline CLEC12A expression also correlates with a higher SDAI at 6 months. In contrast, positive correlations were observed between baseline CLEC12A expression and several cytokines. Moreover, neutrophil and monocyte CLEC12A expression is significantly higher in early rheumatoid arthritis patients at baseline than healthy controls. Circulating neutrophil and monocyte CLEC12A expression correlates with disease activity at baseline and is predictive of SDAI at later stages of the disease indicative of a regulatory role for CLEC12A in RA. [ABSTRACT FROM AUTHOR]

Study Design: Electronic survey.Objective: The aim of this study was to identify the international nuances in surgical treatment patterns for severals lumbar degenerative conditions, specifically, to identify differences in responses in each country groupand different treatment trends across countries.Summary Of Background Data: Significant variations in treatment of lumbar degenerative conditions exist among spine surgeons, related to the lack of established consensus in the literature.Methods: An online survey with preformulated answers was submitted to 52 orthopedic surgeons, 50 neurosurgeons from four different countries (United States, France, Spain, and Germany) regarding five vignette-cases. Cases included: multilevel stenosis, monolevel stenosis, lytic spondylolisthesis, isthmic lysis, and degenerative scoliosis. The variability for each country was calculated according to the Index of Qualitative Variation (IQV = 0: no variability and 1: maximal variability). We used Fleiss kappa (range: from -1, poor agreement, to 1, almost perfect agreement) for assessing the reliability of agreement between the participants concerning specialties, countries, and age groups.Results: For the two stenosis cases, US surgeons were more likely to propose decompression (IQV multilevel = 0.47 and monolevel = 0.32) comparing with European countries more heterogeneous (all IQV >0.70) and more frequently proposing fusion. As regards degenerative scoliosis, all attitudes were extremely heterogeneous with IQV >0.8. Fusion for isthmic spondylolisthesis was more consensual (all IQV <0.63), but attitudes were more heterogeneous for isthmic lysis (IQV ranged from 0.48 to 0.76) with anterior approach proposed in France (37%) and United States (19.2%).The overall interrater agreement was equally slight not only for neurosurgeons (Fleiss Kappa = 0.04) and orthopedic surgeons (Kappa = 0.13), but also for countries (Kappa <0.13) and age groups (Kappa <0.1).Conclusion: In this study, we found substantial agreement for some spinal conditions but a high variability in some others: intranational and international variations were observed, reflecting the lack of literature consensus.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Résumé Les infections opportunistes (IO) sont rares en cas de sarcoïdose (1 à 10 %) et surviennent le plus souvent au cours de sarcoïdose connue ou, plus rarement, la révèlent. Les IO les plus fréquentes sont par ordre décroissant : l’aspergillose pulmonaire, la cryptococcose et les infections mycobactériennes. La corticothérapie systémique représente le facteur de risque le plus fréquent d’IO au cours de la sarcoïdose mais les immunosuppresseurs et les anti-TNFα peuvent aussi être en cause. Le plus souvent, la présentation clinique, le traitement et le devenir des patients ne diffèrent pas des autres conditions favorisant la survenue d’une IO. Néanmoins, certaines présentations atypiques d’IO peuvent mimer une exacerbation de la sarcoïdose et la confusion risque de conduire le clinicien à une intensification de l’immunosuppression, entraînant l’aggravation de l’IO. Le recueil minutieux des antécédents ainsi que la connaissance des indices permettant de différencier une IO d’une exacerbation de la sarcoïdose sont donc des facteurs clés dans la prise en charge de ces patients. Opportunistic infections (OI) are uncommon in sarcoidosis (1 to 10%) and mostly occur in patients with previously diagnosed disease or can rarely be the presenting manifestation. The most common OIs are, in descending order: aspergillosis, cryptococcosis, and mycobacterial infections. Treatment with corticosteroids is the most frequent risk factor for OI occurrence during sarcoidosis but immunosuppressive drugs and therapy with anti-TNFα are also risk factors. Overall, clinical presentation, treatment, and outcome are identical to that occur in other conditions complicated with the occurrence of OIs. However, some atypical presentations of OIs can mimic sarcoidosis exacerbation and misdiagnosis may lead clinicians to increase immunosuppression, causing worsening of the OI. The meticulous collection of patient's history along with factors differentiating OI from sarcoidosis exacerbation is key factor to optimally manage these patients. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical features, treatment, and outcome of autoimmune diseases (AD) in a cohort of patients with thymoma. Design Pathological records from three university hospitals, between 2005 and 2011, were reviewed to identify patients with thymoma. Patients with thymoma and AD were compared with patients with thymoma without AD. Results 47/85 (55%) cases of thymoma had AD, including myasthenia gravis (MG) (n = 33), Hashimoto's thyroiditis (n = 4), Isaac's syndrome (n = 3), Morvan syndrome (n = 2), pure red cell aplasia (n = 2), systemic lupus (n = 2), lichen planus (n = 2), and one case of each following conditions: aplastic anemia, autoimmune hemolytic anemia, Good's syndrome, pemphigus, autoimmune hepatitis, Graves' disease, limbic encephalitis, and inflammatory myopathy. Six patients (7%) presented at least 2 ADs. The median duration of follow-up after surgery was 60 months (40–78 months). In 32 patients, the diagnosis of AD preceded the diagnosis of thymoma, in 9 patients, thymoma was diagnosed at the same time as the AD and 7 patients had been operated on when they developed an AD. We found a significative difference on the Masaoka stage between the MG patients and the patients who present another AD (p = 0.028). No risk factor for developing an AD after thymectomy was identified. Conclusions We describe here the long-term follow-up of a large series of AD related to thymoma. Our results confirm previous data concerning AD occurrence in patients with thymoma and suggest that preexisting autoimmunity is not a risk factor for developing autoimmune manifestations after thymectomy. [ABSTRACT FROM AUTHOR]

Sarcoidosis is an inflammatory disease marked by a paradoxical immune status. The anergic state, which results from various immune defects, contrasts with the inflammatory formation of granulomas. Sarcoidosis patients may be at risk for opportunistic infections (OIs) and a substantial number of cases have been reported, even in untreated sarcoidosis. It is not clear how OIs in patients with sarcoidosis are different from other groups at risk. In this review, we discuss the most common OIs: mycobacterial infection (including tuberculosis), cryptococcosis, progressive multifocal leukoencephalopathy, and aspergillosis. Unlike peripheral lymphocytopenia, corticosteroids are a major risk factor for OIs but the occurrence of Ols in untreated patients suggests more complex predisposing mechanisms. Opportunistic infections presenting with extrapulmonary features are often misdiagnosed as new localizations of sarcoidosis. Aspergillomas mostly develop on fibrocystic lungs. Overall, physicians should be aware of the possible occurrence of OIs during sarcoidosis, even in untreated patients. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility and validity of ultrasonographic measurement of gastric antral cross-sectional area (usCSA) in critically ill patients to predict gastric volume and the use of computed tomography (CT) as a reference to measure gastric volume. Method: This single-center, prospective, cross-sectional study included 55 critically ill patients who had an abdominal CT scan. usCSA measurements were performed within the hour preceding the CT scan. Gastric volumes were measured on the CT scan using semiautomatic software. The feasibility rate, performing conditions (% 'good' and 'poor'), internal and external validity of antral usCSA measurements, performed by an ICU physician, were assessed to predict gastric volume. Results: Antral usCSA measurements were feasible in 95 % of cases and were positively correlated with gastric volume measured by the CT scan when performed in 'good' conditions (65 %) ( r = 0.43). There was good reproducibility of measurements (intraclass correlation coefficient of 0.97, CI 95 % 0.96-0.99) and there was clinically acceptable agreement between measurements performed by radiologists and intensivists (bias −0.12 cm). The receiver operating characteristic curve identified a cutoff value of 3.6 cm that discriminated an 'at-risk stomach' (volume >0.8 mL/kg) at a sensitivity of 76 % and a specificity of 78 %. Conclusions: Ultrasonographic measurement of antral CSA is feasible and reliable in the majority of critically ill patients. This technique could be useful to manage critically ill patients at risk of aspiration or with enteral feeding. [ABSTRACT FROM AUTHOR]

Cytokines play a central role in the pathophysiology of autoimmune and inflammatory diseases. Several cytokines signal through the JAK-STAT pathway, which is now recognized as a major target to inhibit the effect of a wide array of cytokines. JAK inhibitors are increasingly used in the setting of inflammatory and autoimmune diseases. While the currently approved drugs are panJAK inhibitors, more selective small molecules are being developed and tested in various rheumatic disorders. In this extensive review, we present evidence- or hypothesis-based perspectives for these drugs in various rheumatologic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, giant cell arteritis, and autoinflammatory diseases. • Several cytokines signal through the JAK-STAT pathway • JAK inhibition is an efficient strategy for multiple inflammatory or autoimmune diseases. • More selective small molecules are being developed and tested in various rheumatic disorders. [ABSTRACT FROM AUTHOR]

Introduction La fièvre méditerranéenne familiale (FMF) est le syndrome auto-inflammatoire le plus fréquent. Sa physiopathologie repose sur une dérégulation de l’inflammasome pyrine. Nous avons cherché à savoir si l’activation spécifique de la pyrine par des inhibiteurs de kinases permet de distinguer les patients FMF des autres patients. Patients et méthodes Ex vivo, les sécrétions d’interleukine (IL)-1β et les cinétiques de mort cellulaire des monocytes de donneurs sains ( n = 33), de patients FMF ( n = 26) et de patients atteints de pathologies inflammatoires ( n = 24) ont été analysées, en réponse à des inhibiteurs de kinase de la superfamille de la PKC. Les paramètres du test (sensibilité, spécificité, VPP, VPN) ont été calculés. Résultats La sécrétion d’IL-1β était significativement augmentée chez les patients FMF comparés aux donneurs sains et aux sujets atteints de pathologies inflammatoires ( p < 0,001). Parallèlement, la mort cellulaire survenait significativement plus précocement chez les patients FMF que chez les sujets des groupes contrôles ( p < 0,001). L’activation d’autres inflammasomes (NLRP3, NLRC4) ne produisait pas de différences significatives entre les groupes. Les différences de sécrétion d’IL-1β entre les groupes permettaient de discriminer les patients FMF des autres groupes avec une sensibilité de 89 %, une spécificité de 90 %, une VPP de 77 % et une VPN de 96 %. Les cinétiques de mort cellulaires permettaient de discriminer les patients FMF avec une sensibilité de 95 %, une spécificité de 94 %, une VPP de 88 % et une VPN de 98 %. Conclusion Notre test permet de distinguer les patients atteints de FMF avec une spécificité et une sensibilité élevées. Nos résultats ouvrent la voie au développement d’un diagnostic fonctionnel de la FMF qui pourrait être utilisé avant la génétique pour affiner le diagnostic ou après la génétique dans le cas de tests non concluants, qui représentent environ 25 % des cas actuellement. [ABSTRACT FROM AUTHOR]

Loss of oligodendrocytes causes severe neurological damage. Oligodendrogenesis is the production of new oligodendrocytes throughout life and includes several developmental stages starting from oligodendrocyte precursor cells (OPCs). The GPR17-expressing cell population, an important intermediate stage in oligodendrocyte development, acts as a reservoir responding to brain injury and ischemia. GPR17 plays a complex role in oligodendrocyte maturation and response to injury; its activation promotes differentiation into more mature phenotypes. However, our understanding of GPR17-expressing oligodendrocytes in vitro remains limited. No methods have been elucidated for studying these short-lived and changeable cell populations using culture systems. The extracellular matrix (ECM) plays an important role in regulating the proliferation and differentiation of these cells; however, conventional two-dimensional culture systems cannot reproduce the complex structure and environmental conditions of the ECM in vivo. Herein, a culture system with decellularized brain tissue that retains organized ECM scaffolds was introduced to better mimic the in vivo environment. This system enabled the study of interactions between OPCs, ECM, and other cell types. Neurospheres containing progenitor cells that differentiate into oligodendrocyte lineage cells, neurons, and astrocytes were transplanted into decellularized brain slices. The results showed that this method not only promoted stem cell differentiation but also significantly enhanced differentiation into oligodendrocytes when supplemented with oligo buffer. This model system provides a better understanding of the interaction between OPCs and the ECM and a novel approach for studying the differentiation of GPR17-expressing cells, which may be useful for future therapeutic strategies for promoting remyelination and central nervous system repair., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The spatial organization of various cell populations is critical for the major physiological and pathological processes in the kidneys. Most evaluation of these processes typically comes from a conventional 2D tissue cross-section, visualizing a limited amount of cell organization. Therefore, the 2D analysis of kidney biopsy introduces selection bias. The 2D analysis potentially omits key pathological findings outside a 1- to 10-μm thin-sectioned area and lacks information on tissue organization, especially in a particular irregular structure such as crescentic glomeruli. In this study, we introduce an easy-to-use and scalable method for obtaining high-quality images of molecules of interest in a large tissue volume, enabling a comprehensive evaluation of the 3D organization and cellular composition of kidney tissue, especially the glomerular structure. We show that CUBIC and ScaleS clearing protocols could allow a 3D analysis of the kidney tissues in human and animal models of kidney disease. We also demonstrate that the paraffin-embedded human biopsy specimens previously examined via 2D evaluation could be applicable to 3D analysis, showing a potential utilization of this method in kidney biopsy tissue collected in the past. In summary, the 3D analysis of kidney biopsy provides a more comprehensive analysis and a minimized selection bias than 2D tissue analysis. Additionally, this method enables a quantitative evaluation of particular kidney structures and their surrounding tissues, with the potential utilization from basic science investigation to applied diagnostics in nephrology., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Objectives: The mechanisms of mental and neurological diseases have been proposed to be related not only to disorders of the neurons but also to the environment surrounding neurons, such as glial cells and the extracellular matrix (ECM). The chondroitin sulfate (CS) chain, which comprises CS proteoglycans (CSPGs), is one of the major sulfated glycosaminoglycans in the brain. CSPGs play an important role in the development, aging, and pathological conditions of the central nervous system. In particular, CSPGs play critical roles in oligodendrocyte differentiation and cell activity. Conventional two-dimensional culture in a glass chamber hardly replicates the complexity of the ECM structure or mimics in vivo conditions. Therefore, to solve this issue, this study aimed to use a culture system with decellularized tissue as a scaffold of organized ECM, thereby enabling the observation of cell differentiation and interactions between cells and the surrounding ECM., Materials and Methods: We investigated the differentiation potential of the OLP6 cell line using decellularized brain tissue as the substrate., Results: We observed that OLP6 differentiated faster on decellularized brain tissues than on conventional 2D-coated surfaces. The relative mRNA expression levels of CNP , PNP , and MBP as well as CSPGs were increased under 3D culture conditions., Conclusions: Our study provides the first evidence of the advantages of cell culture on decellularized tissues for the investigation of oligodendrocyte differentiation and cell/ECM interactions., Competing Interests: The authors declare that there are no conflicts of interest. All experiments were conducted in compliance with the ARRIVE guidelines., (2023 ©The Juntendo Medical Society.)

Glycosylation is an important mechanism regulating various biological processes, including intercellular signaling and adhesion. α-1,6-fucosyltransferase (Fut8) belongs to a family of enzymes that determine the terminal structure of glycans. Fut8 is widely conserved from Caenorhabditis elegans to humans, and its mutants have been reported in humans, mice, and zebrafish. Although mutants show various symptoms, such as spinal deformity and growth retardation, its effects on skeletal muscles are unknown. We aimed to elucidate the function of Fut8 in skeletal muscle using zebrafish and C2C12 cells for evaluation. We observed that most fut8a morphants died at 2 days post-fertilization (dpf) or in earlier developmental stages even at low concentrations of morpholino oligonucleotides (MOs). Mutant juveniles also had small body sizes, and abnormal myocepta and sarcomere structures, suggesting that Fut8a plays important roles in myogenesis. Moreover, treatment of C2C12 cells with 2-fluorofucose (2FF), a fucosylation inhibitor, during cell differentiation dramatically reduced the expression of myogenic genes, such as Myomaker and other myogenic fusion genes, and inhibited myotube formation. These results indicate that Fut8 is an important factor in myogenesis, and myofusion in particular.