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Background: Epicutaneous immunotherapy (EPIT) is a promising method for treating food allergies. In animal models, EPIT induces sustained unresponsiveness and prevents further sensitization mediated by Tregs. Here, we elucidate the mechanisms underlying the therapeutic effect of EPIT, by characterizing the kinetics of DNA methylation changes in sorted cells from spleen and blood and by evaluating its persistence and bystander effect compared to oral immunotherapy (OIT). Methods: BALB/c mice orally sensitized to peanut proteins (PPE) were treated by EPIT using a PPE‐patch or by PPE‐OIT. Another set of peanut‐sensitized mice treated by EPIT or OIT were sacrificed following a protocol of sensitization to OVA. DNA methylation was analyzed during immunotherapy and 8 weeks after the end of treatment in sorted cells from spleen and blood by pyrosequencing. Humoral and cellular responses were measured during and after immunotherapy. Results: Analyses showed a significant hypermethylation of the Gata3 promoter detectable only in Th2 cells for EPIT from the 4th week and a significant hypomethylation of the Foxp3 promoter in CD62L+ Tregs, which was sustained only for EPIT. In addition, mice treated with EPIT were protected from subsequent sensitization and maintained the epigenetic signature characteristic for EPIT. Conclusions: Our study demonstrates that EPIT leads to a unique and stable epigenetic signature in specific T‐cell compartments with downregulation of Th2 key regulators and upregulation of Treg transcription factors, likely explaining the sustainability of protection and the observed bystander effect. EPIT induces sustained hypermethylation of Gata3 in Th2 cells and demethylation of Foxp3 in CD62L+ Tregs. The epigenetic signature is unique compared to OIT. Gata3 hypermethylation and Foxp3 demethylation correlate with biologic effects, particularly the protection against further sensitizations. [ABSTRACT FROM AUTHOR]

Background: All-soft suture anchors (ASSAs) are commonly used for shoulder labral repair and capsulorrhaphy in patients with shoulder instability. While these anchors may have some specific advantages over other types of suture anchors, little is known about the prevalence and time-dependence of bone cyst formation and tunnel expansion after implantation of ASSAs. The aim of this study was to quantify the proportions of cyst formation and tunnel expansion around ASSAs and to characterize and test for differences in abnormalities observed at different postoperative time points.Methods: Thirty patients who were treated with arthroscopic shoulder stabilization surgery with ASSAs (1.4 mm; JuggerKnot, Biomet) underwent a computed tomography (CT) scan of the operatively treated shoulder at 1 month (10 patients), 6 months (10 patients), or 12 months (10 patients) postoperatively. Demographic and operative data were collected, and CT scans were evaluated for cyst formation, tunnel expansion, and tunnel volume measured in cubic millimeters. Statistical analyses were performed to detect differences in these outcomes among the follow-up groups. All shoulders were stable at all time points of the study, and there were no incidents of recurrent instability during the study period.Results: Ninety-one suture anchors were evaluated in 30 patients. Tunnel expansion was identified in the large majority of patients in the 6-month and 12-month follow-up groups, with a significant increase in these proportions compared with the 1-month follow-up group (p = 0.002). Mean tunnel volumes also significantly increased over the study period (p < 0.001). The presence of cyst formation was negligible in all 3 follow-up cohorts.Conclusions: This study demonstrated low rates of cyst formation but a significantly increased tunnel volume 6 and 12 months after shoulder labral surgery with ASSAs. There was no association with the initial tunnel location. Additional well-controlled studies with longer follow-up are needed to identify potential associations among tunnel expansion, intraoperative technique, and clinical outcomes.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Symptomatic pan-labral or circumferential (360°) tears of the glenohumeral labrum are an uncommon injury. The purpose of the present study was to report the results of surgical treatment of circumferential lesions of the glenoid labrum with use of validated outcome instruments.Methods: From July 2003 to May 2006, forty-one shoulders in thirty-nine patients (thirty-four men and five women) with a mean age of 25.1 years were prospectively enrolled in a multicenter study and were managed for a circumferential (360°) lesion of the glenoid labrum. All patients had a primary diagnosis of pain and recurrent shoulder instability, and all underwent arthroscopic repair of the circumferential labral tear with a mean of 7.1 suture anchors. The outcomes for thirty-nine of the forty-one shoulders were assessed after a mean duration of follow-up of 31.8 months on the basis of the rating of pain and instability on a scale of 0 to 10, a physical examination, and three outcome instruments (the Single Assessment Numeric Evaluation score, the modified American Shoulder and Elbow Surgeons score, and the Short Form-12 score).Results: Significant improvement was noted in terms of the mean pain score (from 4.3 to 1.1), the mean instability score (from 7.3 to 0.2), the mean modified American Shoulder and Elbow Surgeons score (from 55.5 to 89.6), the mean Short Form-12 score (from 75.7 to 90.0), and the mean Single Assessment Numeric Evaluation score (from 36.7 to 88.5). Six shoulders required revision surgery because of recurrent instability (two), recalcitrant biceps tendinitis (two), or postoperative tightness (two). All patients returned to their preinjury activity level.Conclusions: Pan-labral or circumferential lesions are an uncommon yet extensive injury of the glenohumeral joint that may result in recurrent instability and pain. The present study demonstrates that arthroscopic capsulolabral repair with suture anchor fixation can restore the stability of the glenohumeral joint and can provide a reliable improvement in subjective and objective outcome measures. [ABSTRACT FROM AUTHOR]

To study the influence on lipid metabolism and platelet aggregation of the fatty acid isomerization that occurs during heat treatment, weanling rats were fed for 8 wk a diet enriched with 5% isomerized (experimental group) or normal (control group) canola oil. Geometrical isomers of alpha-linolenic acid representing 0.2 g/100 g of the experimental diet were incorporated into liver, platelets, aorta and heart, at the expense of their cis homologue and of 18:2(n-6). The major isomer, 9c,12c,15t-18:3, was also metabolized to 5c,8c,11c,14c,17t-20:5 and to an unknown compound, found in liver, platelets and aorta, which has been identified tentatively as 7c, 10c,13c,16c,19t-22:5. The greater 20:4(n-6)/18:2(n-6) ratio in the liver, platelets and heart of the experimental group than the control group indicated an enhancement of desaturation activities. This induced a higher content of long-chain (n-6) fatty acids in the experimental group. Platelet aggregation tended to be slightly higher (P: = 0.065) in the experimental group. We conclude that 0.2 g of trans isomers of alpha-linolenic acid per 100 g of diet was sufficient to be incorporated and metabolized, thus altering the fatty acid profile of rat tissues. [ABSTRACT FROM AUTHOR]

Introduction L’immunothérapie épicutanée sur peau intacte (EPIT) est une voie thérapeutique des allergies alimentaires en cours de développement. Dans les modèles animaux, la désensibilisation obtenue par l’EPIT est maintenue après arrêt du traitement (tolérance) et prévient de sensibilisations à d’autres allergènes. Le but de ce travail était d’évaluer, dans un modèle de souris sensibilisées, la cinétique des modifications épigénétiques étayant l’effet thérapeutique de l’EPIT et l’induction de tolérance. Méthodes Des souris BALB/c femelles sensibilisées à l’arachide ont été traitées par EPIT ou immunothérapie orale (OIT) ou non traitées pendant 8 semaines. Les prélèvements de rate et sang ont été réalisés aux semaines 1, 2, 4 et 8 du traitement et 8 semaines après arrêt du traitement. Un autre panel de groupes de souris a été analysé après une phase de sensibilisation à un autre allergène, l’ovalbumine. La méthylation de l’ADN a été analysée par pyroséquençage dans les cellules CD4+ purifiées de la rate et du sang. Résultats Dans les cellules CD4+ (rate et sang), une hyperméthylation des îlots CpG associés au promoteur de Gata3 apparaît dès la 4 e semaine d’EPIT, persiste jusqu’à la fin du traitement ( p < 0,05) et se maintient après arrêt du traitement ( p < 0,01). Ce changement n’est pas observé pour les souris traitées avec l’OIT. Une déméthylation des îlots CpG de Foxp3 est observé dans les cellules CD4+ de la rate et du sang, effet persistant jusqu’à la fin de l’EPIT ( p < 0,01) et maintenu après arrêt du traitement ( p < 0,05). Pour l’OIT, la déméthylation atteint un niveau similaire qu’au cours de l’EPIT mais l’effet n’est pas maintenu après l’arrêt du traitement. Dans les souris traitées par EPIT et protégées d’une sensibilisation à l’ovalbumine, la signature épigénétique de l’EPIT est conservée, à savoir l’hyperméthylation de Gata3 et la déméthylation de Foxp3. Conclusion L’EPIT comparée à l’OIT conduit à une signature épigénétique unique et stable permettant une régulation négative de l’expression des gènes de la voie du Th2 et une activation des cellules T régulatrices. Ces mécanismes seraient impliqués dans l’induction de tolérance par EPIT. [ABSTRACT FROM AUTHOR]

Purpose Oxidative Stress (OS) plays a critical role in the pathogenesis of age‐related macular degeneration (AMD), especially by targeting the retinal pigment epithelium (RPE). Dietary habits with high consumption of docosahexaenoic acid (DHA) have been shown to prevent the development and evolution of AMD. Nevertheless, it is still unclear how DHA affects AMD. Our study aimed to investigate the involvement of the PI3K/Akt and m‐TOR/p70‐p85S6K pathways in human RPE cells after induction of OS, and then to assess the effect of DHA in the signaling pathways and in the protection against RPE cell death. Methods For this purpose, we used ARPE‐19 cells exposed to the prooxidant agent, tert‐butyl hydroperoxide (t‐BHP). Results We found that exposing cells to t‐BHP (400µM) showed complete inhibition of Akt and p70/p85S6K active forms. However in cells enriched with DHA (20µM) and then exposed to t‐BHP (400µM), we demonstrated that Akt and p85S6K, but not p70S6K, remained phosphorylated for a longer time after stress. In addition there was a 2.6‐fold decrease in the number of necrotic cells after 48hours of t‐BHP treatment, as assessed by flow cytometry. Conclusion Our study suggests that 1/ PI3K/Akt and m‐TOR/P70‐p85S6K pathways play an important role in OS, 2/DHA protects RPE cells from apoptosis and necrosis triggered by OS by enhancing the phosphorylation of Akt and p85S6K. [ABSTRACT FROM AUTHOR]

Purpose Plasmalogens are particular phospholipids characterized by the presence of a polyunsaturated fatty acid (PUFA) at sn‐2 position of glycerol. Plasmalogen deficiency in mouse leads to developmental abnormalities in retinal vasculature. We propose that liberation of PUFA by the specific calcium‐independent phospholipase A2 (iPLA2), is involved in the mechanism by which plasmalogens control retinal vascular development. To confirm this hypothesis, we performed a comparative study of retinal vascular development in a mouse model of retinal iPLA2 inhibition and a model of plasmalogen deficiency. Methods Vessel and astrocyte networks were visualized on flat‐mounted retinas through immunostaining methods. Results Similar abnormalities were observed in retina of both mouse models. They consisted in an increased number of vessel ramifications at PN14, and in an abnormal glial cells migration from the optic nerve, at PN14 and at PN21. An activation of microglial cells was also observed at adult age. Conclusion These results confirm the implication of plasmalogen in the control of retinal vessel development through PUFA release from their sn‐2 position. [ABSTRACT FROM AUTHOR]

Introduction: La mesure post-prandiale de glycémie capillaire est difficilement réalisée en pratique journalière. Pour recueillir l’information sur les glycémies post-prandiales (GPP), on peut favoriser la réalisation de peu de tests pendant un temps long ou de beaucoup de tests pendant un temps court. Notre but était de comparer, par une étude randomisée, sur une durée de 4 semaines, deux stratégies différentes permettant d’optimiser le recueil des glycémies post-prandiales. Patients et méthodes: Nous avons évalué, chez 60 patients diabétiques nécessitant un contrôle de la GPP, 2 méthodes différentes : [–] Stratégie concentrée- C- (1 glycémie post-prandiale/jour à horaire variable 3 semaines avant la consultation). [–] Stratégie étalée- E- (3 glycémies post-prandiales/jour la semaine précédent la consultation). L’objectif principal de notre étude était d’apprécier le nombre de sujets « observants » avec la stratégie C vs E (nombre de sujets nécessaires : 58 ; puissance de l’étude : 80 %). L’observance se définit par la réalisation pour un sujet d’au moins 50 % des glycémies pré-prandiales et 80 % de glycémies post-prandiales dans les 3 semaines précédant la consultation finale. Résultats: Deux sujets ne sont venus qu’à la consultation initiale et sont non évaluables. Nous avons inclus 29 sujets dans chaque groupe. Les sujets ne différaient pas pour le sexe (C : 17 hommes vs E : 13 hommes), l’âge (C : 62,1±9,9 vs E : 64,4±10,4 ans), l’HbA1c (C : 9,0±1,5 vs E : 8,4±1,6 %) ou le traitement insulinique du diabète (C : 21 sujets vs E : 20 sujets). Le nombre de sujets observants ne différait pas significativement entre les 2 groupes (C : 19 sujets vs E : 22 sujets ; p=0,387). Il n’y avait pas de différence entre les 2 stratégies pour le nombre de GPPréalisées (C : 32±14 vs E : 30±16 ; p=0,626) ou le nombre de glycémies pré-prandiales réalisées (C : 74±15 vs 75±13 ; p=0,756). Conclusion: Les deux stratégies testées sont également performantes pour le recueil des glycémies post-prandiales. [Copyright &y& Elsevier]

Objectives: To determine the outcomes scores of military patients who initially present with a variety of shoulder conditions, identify which scores demonstrate the highest correlation per diagnosis, and determine if a difference exists for patients who went onto surgery.Methods: Two-hundred and seventy five consecutive patients with mean age of 36.5 +/- 12.9 at presentation completed baseline outcomes assessments that included Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons (ASES) Score, Western Ontario Shoulder Instability Index (WOSI), Western Ontario Rotator Cuff Index (WORC), the Simple Shoulder Test (SST), and the Disabilities of the Arm, Shoulder, and Hand Index (DASH). The patients were grouped by clinical, radiographic, and surgical findings into 10 diagnostic categories.Outcomes: The initial mean outcomes scores were SANE 48.8, ASES 50.1, WOSI 1279 (40% normal), WORC 1122.4 (47% normal), SST 6.7, and DASH 33.1. Patients with superior labrum anterior-posterior tears demonstrated the lowest mean scores, followed by instability and rotator cuff tear patients. For all conditions, scores were lower for patients who went onto surgery compared with those managed nonoperatively (p = 0.008).Conclusions: Our findings may be utilized as a baseline to compare and track patient-derived disability across multiple shoulder conditions and serve to define mean diagnosis-specific shoulder patient preoperative scores. [ABSTRACT FROM AUTHOR]