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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: 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]

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]

The purpose of this review is to provide a comprehensive resource for shoulder proprioception assessment and its integration into clinical decision making as well as targeted rehabilitation protocols. Data for this review were acquired from peer-reviewed articles from computerized online databases, namely PubMed and Medline, published between 1906 and 2021. The development of digital/smart phone goniometers can improve shoulder joint range of motion (ROM) measurements and demonstrate comparable measurement accuracy to the universal standard goniometer. The inclinometer offers a portable and cost-effective method for measuring shoulder joint angles and arcs of motion in the vertical plane. Two types of dynamometers, the computerized isokinetic machine and the handheld hydraulic dynamometer, are reliable tools for objective shoulder rotator cuff strength assessment. Motion analysis systems are highly advanced modalities that create three-dimensional models of motion arcs using a series of cameras and reflective beads, offering unparalleled precision in shoulder proprioception measurement; however, they require time-consuming calibration and skilled operators. Advancements in wearable devices and compact mobile technology such as iPhone applications may make three-dimensional motion analysis more affordable and practical for outpatient settings in the future. The complex interplay between proprioception and shoulder dysfunction is not fully understood; however, shoulder proprioception can likely both contribute to and be caused by shoulder pathology. In patients with rotator cuff tears, glenohumeral osteoarthritis, and shoulder instability, clinicians can track proprioception to understand a patient's disease progression or response to treatment. Finally, rehabilitation programs targeting shoulder proprioception have shown promising initial results in restoring function and returning athletes to play.

Introduction: The COVID-19 pandemic has caused unprecedented pressure on medical care resources and access. The aim of this study was to evaluate the time between the cancer symptoms' onset and the first ENT specialist consultation for patients with head and neck (HNC) and salivary glands cancers during the pandemic., Methods: The outcome measures evaluated were time to diagnosis, and time to treatment onset, as well as the COVID-19 impact on the proportion of both cancer patient groups: asymptomatic and advanced stages. This is single-centre retrospective cross-sectional study, including 473 patients who were treated in our University Hospital for HNC and salivary gland cancers, 171 in the COVID-19 pandemic group (C +), and 302 patients in the pre-pandemic group (C-)., Results: There were no significant between-group differences in the delays between cancer symptoms' onset and ENT consultation, diagnostic workup and initial treatment onset, respectively. There was a suggestive reduction in the number of diagnostic panendoscopy performed in the C + group (62%) compared to the C- group (73%) as well as a suggestive increase in the delay to adjuvant radiotherapy onset., Conclusion: The median delay between cancer symptoms' onset and ENT specialist consultation was not affected by the COVID-19 pandemic in our centre. Our results suggest an 11% decrease in diagnostic procedures performed independently, a decrease in the delay between the ENT consultation and surgical treatment onset and a 10-day increase in the delay to adjuvant radiotherapy onset., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Failure rates up to 14% have been reported after arthroscopic posterior capsulolabral repair. It is unknown if revision arthroscopic posterior capsulolabral stabilization has inferior restoration of stability and return to sport when compared with primary repair. Optimal management of failed posterior capsulolabral stabilization is unknown., Purpose: To report outcomes of revision posterior capsulolabral repair and factors that contribute to failure and to determine optimal management of failed posterior stabilization procedures., Study Design: Systematic review; Level of evidence, 4., Methods: A computerized search of the PubMed, EMBASE, and Web of Science databases and manual screening of selected article reference lists were performed in January 2022. Randomized controlled trial, cohort, case-control, and case series studies reporting clinical outcomes of revision arthroscopic posterior capsulolabral repair were eligible. Patient characteristics, indications for revision, intraoperative findings, surgical techniques, and patient-reported outcomes were recorded. Owing to heterogeneity of reported outcomes, data were summarized and presented without pooled statistics., Results: Only 3 of the 990 identified studies met inclusion criteria. The included studies encompassed 26 revision arthroscopic posterior capsulolabral repairs, with follow-up ranging from 2.3 to 5.3 years. The failed index procedure was arthroscopic capsulolabral repair with suture anchors (n = 22) or posterior thermal capsulorrhaphy (n = 4). The primary indications for revision were recurrent instability and pain. Six patients experienced recurrent instability after revision. Patient satisfaction ranged from 15% to 25%., Conclusion: This systematic review of 3 studies demonstrated that the incidence of persistent pain and recurrent instability after revision arthroscopic posterior shoulder stabilization is common, and despite slight improvement in patient-reported outcomes, many patients are dissatisfied with their clinical outcomes. Revision arthroscopic posterior shoulder stabilization appears to have a significant failure rate, and there is need for additional prospective studies to help determine the best intervention for these patients., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: E.B. has received grant support from DJO, education payments from Arthrex and Smith & Nephew, and hospitality payments from Stryker. R.W.W. has received royalties from Responsive Arthroscopy. J.D. has received education payments from Supreme Orthopedic Systems and nonconsulting fees from Arthrex. L.L. has received grant support from DJO and education payments from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Plasmalogens are a specific glycerophospholipid subtype characterized by a vinyl-ether bound at their sn- 1 moiety. Their biosynthesis is initiated in the peroxisome by dihydroxyacetone phosphate-acyltransferase (DHAPAT), which is encoded by the DAPAT gene. Previous studies have shown that plasmalogen-deficient mice exhibit major physiological dysfunctions including several eye defects, among which abnormal vascular development of the retina and a reactive activation of macroglial Müller cells. Interestingly, plasmalogen deficiency in mice is also associated with a reduced expression of brain connexin 43 (Cx43). Cx43 is the main connexin subtype of retinal glial cells and is involved in several cellular mechanisms such as calcium-based gap junction intercellular communication (GJIC) or cell migration. Thus, the aim of our work was 1) to confirm the alteration of Cx43 expression in the retina of plasmalogen-deficient DAPAT -/- mice and 2) to investigate whether plasmalogens are involved in crucial functions of Müller cells such as GJIC and cell migration. First, we found that plasmalogen deficiency was associated with a significant reduction of Cx43 expression in the retina of DAPAT -/- mice in vivo . Secondly, using a siRNA targeting DHAPAT in vitro , we found that a 50%-reduction of Müller cells content in plasmalogens was sufficient to significantly downregulate Cx43 expression, while increasing its phosphorylation. Furthermore, plasmalogen-depleted Müller cells exhibited several alterations in ATP-induced GJIC, such as calcium waves of higher amplitude that propagated slower to neighboring cells, including astrocytes. Finally, in vitro plasmalogen depletion was also associated with a significant downregulation of Müller cells migration. Taken together, these data confirm that plasmalogens are critical for the regulation of Cx43 expression and for characteristics of retinal Müller glial cells such as GJIC and cell migration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Karadayi, Mazzocco, Leclere, Buteau, Gregoire, Belloir, Koudsi, Bessard, Bizeau, Dubus, Fenech, Briand, Bretillon, Bron, Fioramonti and Acar.)

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Background: Stacked screws is a commonly used technique in single-stage revision anterior cruciate ligament (ACL) reconstruction in the setting of bone loss, but there are limited data to support its use., Hypothesis: Two configurations of a biocomposite stacked screws construct have similar fixation strength and linear stiffness as a primary ACL reconstruction construct in a biomechanical model., Study Design: Controlled laboratory study., Methods: A total of 30 porcine legs were divided into 3 groups. Group 1 underwent primary ACL reconstruction with a patellar tendon graft fixed into the femur, with an 8-mm biocomposite interference screw of beta-tricalcium phosphate and poly lactide-co-glycolide. For a revision ACL reconstruction model, groups 2 and 3 had bone tunnels created and subsequently filled with 12-mm biocomposite screws. New bone tunnels were drilled through the filler screw and the surrounding bone, and the patellar bone plug was inserted. Group 2 was fixed with 8-mm biocomposite screws on the side of the graft opposite the filler screw, while group 3 had the interference screw interposed between the graft and the filler screw. The construct was loaded at 1.5 mm/s in line with the tunnel until failure. Load to failure, linear stiffness, and mode of failure were recorded., Results: The mean pullout strength for groups 1, 2, and 3 was 626 ± 145 N, 653 ± 152 N, and 720 ± 125 N, respectively ( P = .328). The mean linear stiffness of the construct in groups 1, 2, and 3 was 71.4 ± 9.9 N/mm, 84.1 ± 11.1 N/mm, and 82.0 ± 10.8 N/mm, respectively. Group 2 was significantly stiffer than group 1 ( P = .037)., Conclusion: Two configurations of a biocomposite stacked screws construct for a single-stage revision ACL reconstruction in the setting of bone loss show a similar fixation strength and linear stiffness to a primary ACL reconstruction at time zero in a porcine model., Clinical Relevance: In the setting of bone loss from tunnel malpositioning, a single-stage revision ACL reconstruction using a stacked screws construct may provide adequate fixation strength and linear stiffness.

Background: Posterior glenohumeral instability is an increasingly recognized cause of shoulder instability, but little is known about the incidence or effect of posterior glenoid bone loss., Purpose: To determine the incidence, characteristics, and failure rate of posterior glenoid deficiency in shoulders undergoing isolated arthroscopic posterior shoulder stabilization., Study Design: Cohort study; Level of evidence, 3., Methods: All patients undergoing isolated posterior labral repair and glenoid-based capsulorrhaphy with suture anchors between 2008 and 2016 at a single institution were identified. Posterior bone deficiency was calculated per the best-fit circle method along the inferior two-thirds of the glenoid by 2 independent observers. Patients were divided into 2 groups: minimal (0%-13.5%) and moderate (>13.5%) posterior bone loss. The primary outcome was reoperation for any reason. The secondary outcomes were military separation and placement on permanent restricted duty attributed to the operative shoulder., Results: A total of 66 shoulders met the inclusion criteria, with 10 going on to reoperation after a median follow-up of 16 months (range, 14-144 months). Of the total shoulders, 86% (57/66) had ≤13.5% bone loss and 14% (9/66) had >13.5%. Patients with moderate posterior glenoid bone loss had significantly greater retroversion (-11.5° vs -4.3°; P = .01). Clinical failure requiring reoperation was seen in 10.5% of patients in the minimal bone deficiency group and 44.4% in the moderate group ( P = .024). There was no difference between groups in rate of military separation or restricted duty. Patients with moderate posterior glenoid bone deficiency were more likely to be experiencing instability instead of pain on initial presentation ( P < .001), were more likely to have a positive Jerk test result ( P = .05), and had increased glenoid retroversion ( P = .01)., Conclusion: In shoulders with moderate glenoid bone deficiency (>13.5%) and increased glenoid retroversion, posterior capsulolabral repair alone may result in higher reoperation rates than in shoulders without bone deficiency.

Communication between neurons and glia plays a major role in nervous tissue homeostasis. It is thought to participate in tuning cholesterol metabolism to cellular demand, which is a critical issue for neuronal health. Cholesterol is a membrane lipid crucial for nervous tissue functioning, and perturbed regulation of its metabolism has been linked to several neurodegenerative disorders. In the brain, 24(S)-hydroxycholesterol (24S-OHC) is an oxysterol synthesized by neurons to eliminate cholesterol, and 24S-OHC has been shown to regulate cholesterol metabolism in astrocytes, glial cells which provide cholesterol to neurons. In the retina, 24S-OHC is also an elimination product of cholesterol produced by neurons, especially the retinal ganglion cells. However, it is not known whether Müller cells, the major macroglial cells of the retina, play the role of cholesterol provider for retinal neurons and whether they respond to 24S-OHC signaling, similarly to brain glial cells. In the present study, primary cultures of rat Müller cells were treated with 0, 0.5 or 1.5 μM 24S-OHC for 48 hours. The levels of cholesterol, precursors and oxysterols were quantified using gas chromatography coupled to flame-ionization detection or mass spectrometry. In addition, the expression of key genes related to cholesterol metabolism was analyzed using RTq-PCR. Müller cells were shown to express many genes linked to cholesterol metabolism, including genes coding for proteins implicated in cholesterol biosynthesis (HMGCR), cholesterol uptake and export via lipoproteins (LDL-R, SR-BI, ApoE and ABACA1) and regulation of cholesterol metabolism (SREBP2 and LXRβ). Cholesterol and several of its precursors and oxidative products were present. CYP27A1, the main retinal enzyme implicated in cholesterol elimination via oxysterol production, was quantified at low transcript levels but neither of its two typical products were detected in Müller cells. Furthermore, our results demonstrate that 24S-OHC has a strong hypocholesterolemic effect in Müller cells, leading to cholesterol depletion (-37 % at 1.5 μM). This was mediated by a decrease in cholesterol synthesis, as illustrated by reduced levels of cholesterol precursors: desmosterol (-38 % at 1.5 μM) and lathosterol (-84 % at 1.5 μM), and strong downregulation of HMGCR gene expression (2.4 fold decrease at 1.5μM). In addition, LDL-R and SR-BI gene expression were reduced in response to 24S-OHC treatment (2 fold and 1.6 fold at 1.5 μM, respectively), suggesting diminished lipoprotein uptake by the cells. On the contrary, there was a dramatic overexpression of ABCA1 transporter (10 fold increase at 1.5 μM), probably mediating an increase in cholesterol efflux. Finally, 24S-OHC induced a small but significant upregulation of the CYP27A1 gene. These data indicate that Müller cells possess the necessary cholesterol metabolism machinery and that they are able to sharply adjust their cholesterol metabolism in response to 24S-OHC, a signal molecule of neuronal cholesterol status. This suggests that Müller cells could be major players of cholesterol homeostasis in the retina via neuron-glia crosstalk.

Background: MicroRNAs (MiRs) play an important role in the pathogenesis of chronic inflammatory diseases. This study is the first to investigate miR expression profiles in purified CD4 + T lymphocytes and CD14 + monocytes from patients with axial spondyloarthritis (axSpA) using a high-throughput qPCR approach., Methods: A total of 81 axSpA patients fulfilling the 2009 ASAS classification criteria, and 55 controls were recruited from October 2014 to July 2017. CD14 + monocytes and CD4 + T lymphocytes were isolated from peripheral blood mononuclear cells. MiR expression was investigated by qPCR using the Exiqon Human MiRnome panel I analyzing 372 miRNAs. Differentially expressed miRNAs identified in the discovery cohort were validated in the replication cohort., Results: We found a major difference in miR expression patterns between T lymphocytes and monocytes regardless of the patient or control status. Comparing disease-specific differentially expressed miRs, 13 miRs were found consistently deregulated in CD14 + cells in both cohorts with miR-361-3p, miR-223-3p, miR-484, and miR-16-5p being the most differentially expressed. In CD4 + T cells, 11 miRs were differentially expressed between patients and controls with miR-16-1-3p, miR-28-5p, miR-199a-5p, and miR-126-3p were the most strongly upregulated miRs among patients. These miRs are involved in disease relevant pathways such as inflammation, intestinal permeability or bone formation. Mir-146a-5p levels correlated inversely with the degree of inflammation in axSpA patients., Conclusions: We demonstrate a consistent deregulation of miRs in both monocytes and CD4 + T cells from axSpA patients, which could contribute to the pathophysiology of the disease with potential interest from a therapeutic perspective.

Glaucoma is a progressive and irreversible blinding neuropathy that is characterized by the loss of retinal ganglion cells (RGCs). Muller Glial Cell (MGC) activation is induced in retinal gliosis. MGCs are the most numerous glial cells in the retina and one of their roles is to sustain cholesterol homeostasis. 24S-hydroxycholesterol (24S-OHC) is one of the form of cholesterol elimination from the retina and is overexpressed during glaucoma. The objective of this study was to determine whether 24S-OHC triggers MGC membrane dynamics involving lipid rafts and contributes to gliosis at early and late time points. A proteomic analysis was carried out by nanoLC-MS/MS in raft and non-raft fractions from MGCs after treatment with 24S-OHC (10μM). The expression of structural and functional proteins was further analyzed by Western-blotting, as well as the levels of GM3 ganglioside by LC-MS. Cholesterol, sphingomyelin, saturated fatty acids and ganglioside GM3 are enriched in the rafts fractions in MGCs. Caveolin-1, flotillin-1, connexin-30 and -43 are localized in the MGCs rafts. Proteins implicated in adhesion or oxidative stress pathways in raft fractions were up and down-regulated by the treatment. Our data showed that 24S-OHC induced early changes in protein distribution in raft microdomains; however, further studies are needed to better characterize the surrounded mechanisms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Patella-femoral dislocations, although rare, can result in functionally limiting symptoms and limited return to prior activity levels. The purpose of this study is to report outcomes of a three-in-one patellar realignment surgery for treatment of recurrent patellar instability in a young, active duty military population., Methods: We conducted a retrospective chart review of all patients who underwent our senior author's three-in-one patellar realignment surgery for recurrent patellar instability in the setting of underlying anatomic malalignment. Our primary outcome measure was the rate of recurrent instability. Secondary outcome measures included rate of return to full unrestricted active duty military service and the functional outcome scores., Results: A total of 13 patients with an average follow-up of 16 months were included in this study. During the follow-up period, there were no reported instability events (either dislocation or subluxation). Three (23%) patients were separated secondary to issues with their operative knee and two additional patients were no longer on active duty at time of final follow-up. Six patients had paired (pre- and postoperative) Single Assessment Numerical Evaluation scores which showed a statistically significant improvement (p < 0.05) between the median pre- and postoperative Single Assessment Numerical Evaluation scores of 45 and 85, respectively., Conclusion: Our study demonstrates that the described patellar realignment procedure is effective at substantially reducing and possibly eliminating the symptoms of recurrent instability and allows a modest return to unrestricted active duty., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Background: Humeral avulsion of the glenohumeral ligament (HAGL) is an infrequent but significant contributor to shoulder dysfunction, instability, and functional loss., Purpose: To prospectively identify patients with HAGL lesions and then conduct retrospective evaluation of the clinical history, examination findings, and surgical outcomes of these patients., Study Design: Case series; Level of evidence, 4., Methods: Over a 6-year period (2006-2011), patients with shoulder dysfunction and a HAGL lesion that was confirmed via magnetic resonance arthrogram (MRA) were prospectively evaluated with a minimum 2-year follow-up. Patient demographics, presentation, examination, and surgical findings were documented. Outcomes of return to activity as well as Western Ontario Shoulder Instability Index (WOSI) and Single Assessment Numeric Evaluation (SANE) scores were recorded at final follow-up. Anterior HAGL (aHAGL) lesions were repaired with a partial subscapularis tenotomy approach, while reverse (rHAGL) lesions were repaired arthroscopically., Results: Of 28 patients, 27 (96%) completed the study requirements at a mean of 36.2 months (range, 24-68 months). The sample contained 12 females (44%) and 15 males (56%), who had a mean age of 24.9 years (range, 18-34 years). The chief complaint reported was pain in 23 patients (85%), while only 4 (15%) patients complained primarily of recurrent instability symptoms. Fourteen patients (52%) had aHAGL lesions, 10 patients (37%) had rHAGL lesions, and 3 patients (11%) had combined aHAGL and rHAGL lesions. Ten patients (37%) had concomitant HAGL lesions and labral tears, whereas 17 patients (63%) had isolated HAGL lesion without labral tear. The 17 patients (63%) with aHAGL lesions or combined lesions underwent a partial subscapularis tenotomy approach, while the remaining 10 patients (37%) with rHAGL lesions underwent arthroscopic surgical repair. After surgery, WOSI outcomes improved from 54% to 88% and SANE outcomes improved from 50% to 91% ( P < .01 for both), with no reports in recurrence of instability symptoms at final follow-up., Conclusion: This study demonstrated that patients with symptomatic HAGL lesions predominantly report shoulder pain and dysfunction, with few chief complaints of recurrent instability complaints. After surgery, patients showed predictable return to full activity, improvement in objective and patient-reported outcomes, and satisfaction with treatment outcome.

Circulating cell-free DNA (ccfDNA) bears great promise as biomarker for personalized medicine, but ccfDNA is present only at low levels in the plasma or serum of cancer patients. E-ice-COLD-PCR is a recently developed enrichment method to detect and identify mutations present at low-abundance in clinical samples. However, recent studies have shown the importance to accurately quantify low-abundance mutations as clinically important decisions will depend on certain mutation thresholds. The possibility for an enrichment method to accurately quantify the mutation levels remains a point of concern and might limit its clinical applicability. In the present study, we compared the quantification of KRAS mutations in ccfDNA from metastatic colorectal cancer patients by E-ice-COLD-PCR with two digital PCR approaches. For the quantification of mutations by E-ice-COLD-PCR, cell lines with known mutations diluted into WT genomic DNA were used for calibration. E-ice-COLD-PCR and the two digital PCR approaches showed the same range of the mutation level and were concordant for mutation levels below the clinical relevant threshold. E-ice-COLD-PCR can accurately detect and quantify low-abundant mutations in ccfDNA and has a shorter time to results making it compatible with the requirements of analyses in a clinical setting without the loss of quantitative accuracy., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pectoralis minor (PM) tightness has been linked to pain and dysfunction of the shoulder joint secondary to anterior tilt and internal rotation of the scapula, thus causing secondary impingement of the subacromial space., Purpose: To describe outcomes pertaining to nonoperative and operative treatment via surgical release of the PM tendon for pathologic PM tightness in an active population., Study Design: Case series; Level of evidence, 4., Methods: Over a 3-year period, a total of 46 patients were enrolled (mean age, 25.5 years; range, 18-33 years). Inclusion criteria consisted of symptomatic shoulder pain, limited range of overhead motion, inability to participate in overhead lifting activities, and examination findings consistent with scapular dysfunction secondary to a tight PM with tenderness to palpation of the PM tendon. All patients underwent a lengthy physical therapy and stretching program (mean, 11.4 months; range, 3-23 months), which was followed by serial examinations for resolution of symptoms and scapular tilt. Of the 46 patients, 6 (13%) were unable to adequately stretch the PM and underwent isolated mini-open PM release. Outcomes were assessed with scapula protraction measurements and pain scales as well as American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) scores., Results: Forty of the 46 patients (87%) resolved the tight PM and scapular-mediated symptoms with a dedicated therapy program (pre- and posttreatment mean outcome scores: 58 and 91 [ASES], 50 and 90 [SANE], 4.9 and 0.8 [VAS]; P < .01 for all), but 6 patients were considered nonresponders (mean score, 48 [ASES], 40 [SANE], 5.9 [VAS]) and elected to have surgical PM release, with improved scores in all domains (mean score, 89 [ASES], 90.4 [SANE], 0.9 [VAS]; P < .01) at final follow-up of 26 months (range, 25-30 months). Additionally, protraction of the scapula improved from 1.2 to 0.3 cm in a mean midline measurement from the chest wall preoperatively to postoperatively ( P < .01), similar to results in nonoperative responders. No surgical complications were reported, and all patients returned to full activities., Conclusion: In most patients, PM tightness can be successfully treated with a nonoperative focused PM stretching program. However, in refractory and pathologically tight PM cases, this series demonstrates predictable return to function with notable improvement in shoulder symptoms after surgical release of the PM. Additional research is necessary to evaluate the long-term efficacy of isolated PM treatment.

Modified forms of citrus pectin possess anticancer properties. However, their mechanism of action and the structural features involved remain unclear. Here, we showed that citrus pectin modified by heat treatment displayed cytotoxic effects in cancer cells. A fractionation approach was used aiming to identify active molecules. Dialysis and ethanol precipitation followed by HPLC analysis evidenced that most of the activity was related to molecules with molecular weight corresponding to low degree of polymerization oligogalacturonic acid. Heat-treatment of galacturonic acid also generated cytotoxic molecules. Furthermore, heat-modified galacturonic acid and heat-fragmented pectin contained the same molecule that induced cell death when isolated by HPLC separation. Mass spectrometry analyses revealed that 4,5-dihydroxy-2-cyclopenten-1-one was one cytotoxic molecule present in heat-treated pectin. Finally, we synthesized the enantiopure (4R,5R)-4,5-dihydroxy-2-cyclopenten-1-one and demonstrated that this molecule was cytotoxic and induced a similar pattern of apoptotic-like features than heat-modified pectin., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The lack of plasticity of neurons to respond to dietary changes, such as high fat and high fructose diets, by modulating gene and protein expression has been associated with functional and behavioral impairments that can have detrimental consequences. The inhibition of high fat-induced rewiring of hypothalamic neurons induced obesity. Feeding rodents with high fructose is a recognized and widely used model to trigger obesity and metabolic syndrome. However the adaptive response of the retina to short term feeding with high fructose is poorly documented. We therefore aimed to characterize both the functional and gene expression changes in the neurosensory retina of Brown Norway rats fed during 3 and 8 days with a 60%-rich fructose diet (n = 16 per diet and per time point). Glucose, insulin, leptin, triacylglycerols, total cholesterol, HDL-cholesterol, LDL-cholesterol and fructosamine were quantified in plasma (n = 8 in each group). Functionality of the inner retina was studied using scotopic single flash electroretinography (n = 8 in each group) and the individual response of rod and cone photoreceptors was determined using 8.02 Hz Flicker electroretinography (n = 8 in each group). Analysis of gene expression in the neurosensory retina was performed by Affymetrix genechips, and confirmed by RT-qPCR (n = 6 in each group). Elevated glycemia (+13%), insulinemia (+83%), and leptinemia (+172%) was observed after 8 days of fructose feeding. The cone photoreceptor response was altered at day 8 in high fructose fed rats (Δ = 0.5 log unit of light stimulus intensity). Affymetrix analysis of gene expression highlighted significant modulation of the pathways of eIF2 signaling and endoplasmic reticulum stress, regulation of eIF4 and p70S6K signaling, as well as mTOR signaling and mitochondrial dysfunction. RT-qPCR analysis confirmed the down regulation of Crystallins, Npy, Nid1 and Optc genes after 3 days of fructose feeding, and up regulation of End2. Meanwhile, a trend towards an increased expression of αA- and αB-crystallin proteins was observed at day 8. Our results are consistent with early alterations of the functioning and gene expression in the retina in a pro diabetogenic environment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)