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Most known thioredoxin-type proteins (Trx) participate in redox pathways, using two highly conserved cysteine residues to catalyze thiol-disulfide exchange reactions. Here we demonstrate that the so far unexplored Trx2 from African trypanosomes (Trypanosoma brucei) lacks protein disulfide reductase activity but functions as an effective temperature-activated and redox-regulated chaperone. Immunofluorescence microscopy and fractionated cell lysis revealed that Trx2 is located in the mitochondrion of the parasite. RNA-interference and gene knock-out approaches showed that depletion of Trx2 impairs growth of both mammalian bloodstream and insect stage procyclic parasites. Procyclic cells lacking Trx2 stop proliferation under standard culture conditions at 27°C and are unable to survive prolonged exposure to 37°C, indicating that Trx2 plays a vital role that becomes augmented under heat stress. Moreover, we found that Trx2 contributes to the in vivo infectivity of T. brucei. Remarkably, a Trx2 version, in which all five cysteines were replaced by serine residues, complements for the wildtype protein in conditional knock-out cells and confers parasite infectivity in the mouse model. Characterization of the recombinant protein revealed that Trx2 can coordinate an iron sulfur cluster and is highly sensitive towards spontaneous oxidation. Moreover, we discovered that both wildtype and mutant Trx2 protect other proteins against thermal aggregation and preserve their ability to refold upon return to non-stress conditions. Activation of the chaperone function of Trx2 appears to be triggered by temperature-mediated structural changes and inhibited by oxidative disulfide bond formation. Our studies indicate that Trx2 acts as a novel chaperone in the unique single mitochondrion of T. brucei and reveal a new perspective regarding the physiological function of thioredoxin-type proteins in trypanosomes.

Among the lifestyle interventions, the physical activity (PA) has emerged as an adjuvant non-pharmacological treatment improving mental and physical health in patients with schizophrenia (SZPs) and increasing the hippocampus (HCP) volume. Previously investigated PA programs have been face-to-face, and not necessary adapted to patients' physiological fitness. We propose an innovative 16-week adapted PA program delivered by real-time videoconferencing (e-APA), allowing SZPs to interact with a coach and to manage their physical condition. The primary goal was to demonstrate a greater increase of total HCP volumes in SZPs receiving e-APA compared to that observed in a controlled group. The secondary objectives were to demonstrate the greater effects of e-APA compared to a controlled group on HCP subfields, cardiorespiratory fitness, clinical symptoms, cognitive functions, and lipidic profile. Thirty-five SZPs were randomized to either e-APA or a controlled group receiving a health education program under the same conditions (e-HE). Variables were assessed at pre- and post-intervention time-points. The dropout rate was 11.4%. Compared to the e-HE group, the e-APA group did not have any effect on the HCP total volumes but increased the left subiculum volume. Also, the e-APA group significantly increased cardiorespiratory fitness (VO 2 max), improved lipidic profile and negative symptoms but not cognitive functions. This study demonstrated the high feasibility and multiple benefits of a remote e-APA program for SZPs. e-APA may increase brain plasticity and improve health outcomes in SZPs, supporting that PA should be an add-on therapeutic intervention. ClinicalTrial.gov on 25 august 2017 (NCT03261817)., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess rates of traversing barriers to care to access optimal clinical outcomes in people with migraine internationally., Background: People in need of medical care for migraine should consult a health care professional knowledgeable in migraine management, obtain an accurate diagnosis, and receive an individualized treatment plan, which includes scientific society guideline-recommended treatments where appropriate., Methods: The Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study was a cross-sectional, web-based survey conducted from July 2021 through March 2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States (US). Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria for migraine and had Migraine Disability Assessment Scale (MIDAS) scores of ≥ 6 (i.e., mild, moderate, or severe disability) were deemed to need medical care and were included in this analysis. Minimally effective treatment required that participants were currently consulting a health care professional for headache (barrier 1), reported an accurate diagnosis (barrier 2), and reported use of minimally appropriate pharmacologic treatment (barrier 3; based on American Headache Society 2021 Consensus Statement recommendations). Proportions of respondents who successfully traversed each barrier were calculated, and chi-square tests were used to assess overall difference among countries., Results: Among 14,492 respondents with migraine, 8,330 had MIDAS scores of ≥ 6, were deemed in need of medical care, and were included in this analysis. Current headache consultation was reported by 35.1% (2926/8330) of respondents. Compared with the US, consultation rates and diagnosis rates were statistically significantly lower in all other countries except France where they were statistically significantly higher. Total appropriate treatment rates were also statistically significantly lower in all other countries compared with the US except France, which did not differ from the US. All 3 barriers were traversed by only 11.5% (955/8330) of respondents, with differences among countries (P < 0.001)., Conclusions: Of people with migraine in need of medical care for migraine, less than 15% traverse all 3 barriers to care. Although rates of consultation, diagnosis, and treatment differed among countries, improvements are needed in all countries studied to reduce the global burden of migraine., Trial Registration: NA., (© 2024. The Author(s).)

Drivers of poor sexual health outcomes among Black heterosexual man are poorly understood. Previous research has identified a need to understand Black men's behavioral experiences and motivators in the UK. This study aimed to address this gap through a phenomenological exploration of the sexual health experiences and motivators of Black heterosexual men with experience of higher-risk sexual behaviors living in London. Semi-structured interviews were conducted with 10 participants (18-58 years) recruited through barbershops. Reflexive thematic analysis was used to analyze the data. Five themes were generated. For relevance, three themes are discussed in this paper: 1) The Black Man's Battle; 2) Sexual Socialization; and 3) Sexual Behaviors, Relationships, and Health. Race and gender combined to shape experience of sexual socialization. Exposure to explicit media content from a young age promoted multiple sexual partners. Racist sexual stereotypes exposed participants to fetishization and created pressure to meet sexual expectations. Condom use motivators were complex and multifaceted. Experience of institutional racism created a lack of trust in services. However, actual experiences with sexual health services were positive and counteracted the mistrust created by racism. Sexual health services should better tailor their work to Black heterosexual men and diversify their offer. Services should collaborate with Black community organizations to deliver services outside clinical settings.

Background: Few studies of migraine have evaluated migraine disability across multiple countries using the same methodology., Methods: This cross-sectional, web-based survey was conducted in 2021-2022 in Canada, France, Germany, Japan, UK and USA. Respondents with migraine were identified based on modified International Classification of Headache Disorders, 3rd edition, criteria. Headache features (Migraine Symptom Severity Score (MSSS, range: 0-21), presence of allodynia (Allodynia Symptom Checklist, ASC-12)) and migraine burden (Patient Health Questionnaire-4 (PHQ-4), Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1), Work Productivity and Activity Impairment (WPAI) questionnaire) were evaluated., Results: Among 14,492 respondents with migraine across countries, the mean ± SD MSSS was 15.4 ± 3.2 and 48.5% (7026/14,492) of respondents had allodynia based on ASC-12. Of all respondents living with migraine, 35.5% (5146/14,492) reported moderate to severe anxiety and/or depression symptoms. Mean ± SD MSQ v2.1 Role Function-Restrictive, Role Function-Preventive and Emotional Function domain scores were 60.7 ± 22.9, 71.5 ± 23.0 and 65.1 ± 27.2, respectively. The WPAI mean ± SD percentages of respondents who missed work or worked impaired as a result of migraine were 6.8 ± 18.1% and 41.0 ± 30.1%, respectively., Conclusions: For every country surveyed, migraine was associated with high levels of symptom severity, with allodynia and with substantial burden., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Zaza Katsarava, MD, has been a speaker and/or consultant for, and/or received research support from Allergan, Amgen/Novartis, Eli Lilly, Merck and Teva. Dawn C. Buse, PhD, has received grant support and honoraria from AbbVie, Amgen, Biohaven, Collegium, Eli Lilly, Lundbeck, Teva and Theranica and for work on the editorial board of Current Pain and Headache Reports and is the national principal investigator in the United States for the CaMEO-I Study. Elizabeth Leroux, MD, has received speaker fees and consulting fees from Allergan, Eli Lilly and Teva Neuroscience; consulting fees from Aralez Pharmaceuticals, McKesson Canada and Medscape; speaking fees, consulting fees and reimbursement for travel from Novartis; and reimbursement for travel from IHS-GPAC. Michel Lanteri-Minet, MD, reports personal fees for advisory boards, speaker panels, or investigation studies from Allergan, Amgen, Astellas, ATI, BMS, Boehringer, Boston Scientific, CoLucid, Convergence, GlaxoSmithKline, Grunenthal, IPSEN, Lilly, Lundbeck, Medtronic, Menarini, MSD, Novartis, Orion Pharma, Pfizer, Reckitt Benckiser, Saint-Jude, Salvia BioElectronics, Sanofi-Aventis, Teva, UCB, UPSA and Zambon. Fumihiko Sakai, MD, is a consultant, speaker or scientific advisor for Amgen, Eisai, Eli Lilly, Otsuka and Teva, and the national principal investigator in Japan for the CaMEO-I Study. Manjit Matharu, MD, serves on the advisory board for Abbott, AbbVie, Eli Lilly, Lundbeck, Medtronic, Pfizer, Salvia and Teva; has received payment for the development of educational presentations from AbbVie, electroCore, Eli Lilly, Novartis and Teva; and is the national principal investigator in the United Kingdom for the CaMEO-I Study. Aubrey Manack Adams, PhD, and Karen Carr, PhD, are employees of AbbVie and may hold AbbVie stock. Kristina M. Fanning, PhD, is managing director of MIST Research, which has received research funding from AbbVie, Allay Lamp, NYC Langone Health, Juva Health and GlaxoSmithKline via grants to the National Headache Foundation. Richard B. Lipton, MD, receives research support from the Marx Foundation, the National Headache Foundation, the National Institutes of Health and the US Food and Drug Administration. He serves as a consultant or advisory board member for or has received honoraria or research support from AbbVie/Allergan, Amgen, Biohaven, Dr Reddy's Laboratories (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Teva, Vector and Vedanta Research; receives royalties from Informa and Wolff's Headache, 8th edition (Oxford University Press, 2009); holds stock/options in Axon, Biohaven, CoolTech and Manistee; and is the overall principal investigator for the CaMEO-I Study.

Schizophrenia is associated with changes in white matter (WM) integrity and with reduced life expectancy, in part because of the cardiometabolic side effects of antipsychotics. Physical activity (PA) has emerged as a candidate lifestyle intervention that is safe and effective. The study aimed to assess how an adapted PA program delivered remotely by web (e-APA) improved WM integrity in patients with schizophrenia (SZPs) and healthy controls (HCs) and to evaluate associations among WM integrity, cardiorespiratory fitness, and symptom severity. This longitudinal study was conducted over 16 weeks with 31 participants (18 SZPs and 13 HCs). Diffusion tensor imaging and tract-based spatial statistics were employed to assess WM integrity. Cardiorespiratory fitness was measured by maximal oxygen uptake (VO 2 max), and assessments for clinical symptoms included the Positive and Negative Syndrome Scale, Self-evaluation of Negative Symptoms and the Brief Negative Syndrome Scale (BNSS). Only the SZPs had significantly increased WM integrity after the e-APA program, with increased fractional anisotropy and decreased radial diffusivity in fasciculi involved in motor functions and language process. Furthermore, decreased negative symptoms assessed with BNSS were associated with greater WM integrity following the program. These findings suggest that e-APA may improve WM integrity abnormalities and support e-APA as a promising therapeutic strategy.

Objective: This study evaluated the frequency and clinical impact of thromboembolic complications after frozen elephant trunk aortic arch repair using the Thoraflex device (Terumo Aortic)., Methods: A total of 128 consecutive patients (mean age 67.9 ± 13.7 years, 31.0% female) underwent frozen elephant trunk aortic arch repair using the Thoraflex device between September 2014 and May 2021 in 4 Canadian centers. Patient baseline characteristics, intraoperative details, and frozen elephant trunk thromboembolic complications were collected retrospectively and analyzed., Results: Fifteen patients (11.7%) had thrombus visualized within the frozen elephant trunk stent graft on imaging (n = 8; 53.3%) or had a thromboembolic event (n = 9; 60.0%) before hospital discharge. Sites of embolism were mesenteric (n = 8; 88.9%), renal (n = 4; 44.4%), and iliofemoral (n = 1; 11.1%). Patients who experienced thromboembolic complications were more likely to have a history of autoimmune disease (n = 3; 20.0% vs n = 2; 1.8%; P = .01) and implantation of a longer frozen elephant trunk stent graft (150 mm vs 100 mm) (n = 13; 86.7% vs n = 45; 39.8%; P < .001). All patients with thromboembolic complications received therapeutic anticoagulation, and a smaller proportion required an open surgical (n = 5; 33.3%) or an endovascular (n = 2; 13.3%) intervention. Radiographic resolution of thromboembolic complications was observed in 86.7% of patients (n = 13). In-hospital mortality occurred in 1 patient, stroke occurred in 1 patient, and transient spinal cord injury occurred in 1 patient., Conclusions: Thromboembolic complications occur more often than previously recognized after frozen elephant trunk aortic arch repair using the Thoraflex device and are associated with increased rates of surgical and endovascular reintervention. Prevention and management of these complications require further study., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Individuals with migraine frequently experience pre- and post-headache symptoms. This analysis aimed to characterize the relative frequency and burden of pre- and post-headache symptoms in people with migraine using data collected through the Chronic Migraine Epidemiology and Outcomes - International Study., Methods: This cross-sectional, observational, web-based survey was conducted in 2021-2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States. Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria were offered the opportunity to participate. Information collected included migraine-related disability, depression/anxiety symptoms, cutaneous allodynia, activity limitations, and acute treatment optimization. Respondents indicated how often they had pre- or post-headache symptoms using a 5-point scale, ranging from 0 to 4, with a rating of 2 or higher classified as a pre- or post-headache symptom case. Modeling was used to examine relationships with monthly headache days (MHDs) and activity limitations during pre-headache and post-headache phases., Results: Among a total of 14,492 respondents, pre-headache symptoms were reported by 66.9%, while post-headache symptoms were reported by 60.2%. Both pre-headache and post-headache symptoms were reported by 49.5% of respondents, only pre-headache by 17.4%, only post-headache by 10.7%, and neither pre- nor post-headache symptoms by 22.4%. Compared with respondents who experienced only pre- or post-headache symptoms, respondents who experienced both pre- and post-headache symptoms had the highest rates of 4-7, 8-14, and ≥ 15 monthly headache days (23.1%, 14.1%, and 10.9%, respectively). Of respondents with both pre- and post-headache symptoms, 58.5% reported moderate-to-severe disability, 47.7% reported clinically significant symptoms of depression, 49.0% reported clinically significant symptoms of anxiety, and 63.8% reported cutaneous allodynia with headache (ASC-12). Moderate-to-severe activity limitations were reported during the pre-headache (29.5%) and post-headache phases (27.2%). For all outcomes modeled, after controlling for covariates, having pre-headache symptoms, post-headache symptoms, or both were associated with worse outcomes than having neither., Conclusions: Pre- and post-headache phases of migraine are common, carry unrecognized burden, and may be a target for treatment., (© 2023. The Author(s).)

Skeletal muscles are large syncytia made up of many bundled myofibers that produce forces and enable body motion. Drosophila is a classical model to study muscle biology. The combination of both Drosophila genetics and advanced omics approaches led to the identification of key conserved molecules that regulate muscle morphogenesis and regeneration. However, the transcriptional dynamics of these molecules and the spatial distribution of their messenger RNA within the syncytia cannot be assessed by conventional methods. Here we optimized an existing single-molecule RNA fluorescence in situ hybridization (smFISH) method to enable the detection and quantification of individual mRNA molecules within adult flight muscles and their muscle stem cells. As a proof of concept, we have analyzed the mRNA expression and distribution of two evolutionary conserved transcription factors, Mef2 and Zfh1/Zeb. We show that this method can efficiently detect and quantify single mRNA molecules for both transcripts in the muscle precursor cells, adult muscles, and muscle stem cells.

Background: The Chronic Migraine Epidemiology and Outcomes-International study provides insight into people with migraine in multiple countries., Methods: This cross-sectional, observational, web-based cohort study was conducted in Canada, France, Germany, Japan, United Kingdom, and United States. An initial Screening Module survey solicited general healthcare information from a representative sample and identified participants with migraine based on modified International Classification of Headache Disorders-3 criteria; those with migraine completed a detailed survey based on validated migraine-specific assessments., Results: Among 90,613 people who correctly completed the screening surveys, 76,121 respondents did not meet the criteria for migraine, while 14,492 did. Among respondents with migraine, mean age ranged from 40 to 42 years. The median number of monthly headache days ranged from 2.33 to 3.33 across countries, while the proportion of respondents with moderate-to-severe disability (measured by Migraine Disability Assessment) ranged from 30% (Japan) to 52% (Germany). The proportion of respondents with ≥15 monthly headache days ranged from 5.4% (France) to 9.5% (Japan). Fewer than half of respondents with migraine in each country reported having received a migraine diagnosis., Conclusion: These results demonstrated high rates of migraine-related disability and underdiagnosis of migraine across six countries. This study will characterize country-level burden, treatment patterns, and geographical differences in care.

Tauopathies are neurodegenerative disorders involving the accumulation of tau isoforms in cell subpopulations such as astrocytes. The origins of the 3R and 4R isoforms of tau that accumulate in astrocytes remain unclear. Extracellular vesicles (EVs) were isolated from primary neurons overexpressing 1N3R or 1N4R tau or from human brain extracts (progressive supranuclear palsy or Pick disease patients or controls) and characterized (electron microscopy, nanoparticle tracking analysis (NTA), proteomics). After the isolated EVs were added to primary astrocytes or human iPSC-derived astrocytes, tau transfer and mitochondrial system function were evaluated (ELISA, immunofluorescence, MitoTracker staining). We demonstrated that neurons in which 3R or 4R tau accumulated had the capacity to transfer tau to astrocytes and that EVs were essential for the propagation of both isoforms of tau. Treatment with tau-containing EVs disrupted the astrocytic mitochondrial system, altering mitochondrial morphology, dynamics, and redox state. Although similar levels of 3R and 4R tau were transferred, 3R tau-containing EVs were significantly more damaging to astrocytes than 4R tau-containing EVs. Moreover, EVs isolated from the brain fluid of patients with different tauopathies affected mitochondrial function in astrocytes derived from human iPSCs. Our data indicate that tau pathology spreads to surrounding astrocytes via EVs-mediated transfer and modifies their function.

During development of a drug, the requirement of evaluating the proarrhythmic risk and delayed repolarization needs to be fulfilled. Would it be possible to create an alternative to a thorough QT (TQT) study or is there a need to perform a dedicated TQT study? How is an alternative approach generated, what information is available, and which instructions are considered missing today to generate such an approach? This tutorial describes the considerations and path followed to create an early and feasible alternative to a TQT study using experience-based insights from a successful application to the US Food and Drug Administration for GLPG1972, an ADAMTS-5 inhibitor, and discusses the approach used in light of the current guidelines and literature., (© 2022 Galapagos NV. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: To assess real-world effectiveness, safety, and usage of erenumab in Canadian patients with episodic and chronic migraine with prior ineffective prophylactic treatments., Background: In randomized controlled trials, erenumab demonstrated efficacy for migraine prevention in patients with ≤4 prior ineffective prophylactic migraine therapies. The "Migraine prevention with AimoviG: Informative Canadian real-world study" (MAGIC) assessed real-world effectiveness of erenumab in Canadian patients with migraine., Methods: MAGIC was a prospective open-label, observational study conducted in Canadian patients with chronic migraine (CM) and episodic migraine (EM) with two to six categories of prior ineffective prophylactic therapies. Participants were administered 70 mg or 140 mg erenumab monthly based on physician's assessment. Migraine attacks were self-assessed using an electronic diary and patient-reported outcome questionnaires. The primary outcome was the proportion of subjects achieving ≥50% reduction in monthly migraine days (MMD) after the 3-month treatment period., Results: Among the 95 participants who mostly experienced two (54.7%) or three (32.6%) prior categories of ineffective prophylactic therapies and who initiated erenumab, treatment was generally safe and well tolerated; 89/95 (93.7%) participants initiated treatment with 140 mg erenumab. At week 12, 32/95 (33.7%) participants including 17/64 (26.6%) CM and 15/32 (48.4%) EM achieved ≥50% reduction in MMD while 30/86 (34.9%) participants including 19/55 (34.5%) CM and 11/31 (35.5%) EM achieved ≥50% reduction in MMD at week 24. Through patient-reported outcome questionnaires, 62/95 (65.3%) and 45/86 (52.3%) participants reported improvement of their condition at weeks 12 and 24, respectively. Physicians observed improvement in the condition of 78/95 (82.1%) and 67/86 (77.9%) participants at weeks 12 and 24, respectively., Conclusion: One-third of patients with EM and CM achieved ≥50% MMD reduction after 3 months of erenumab treatment. This study provides real-world evidence of erenumab effectiveness, safety, and usage for migraine prevention in adult Canadian patients with multiple prior ineffective prophylactic treatments., (© 2022 Novartis Pharmaceuticals Canada Inc. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be potential shuttles. We assessed this in humans by preparing vesicles from fluids (brain-derived enriched EVs [BD-EVs]). These latter were isolated from different brain regions in various tauopathies, and their seeding potential was assessed in vitro and in vivo. We observed considerable heterogeneity among tauopathies and brain regions. The most striking evidence was coming mainly from Alzheimer's disease where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. The results support the hypothesis that BD-EVs participate in the prion-like propagation of tau pathology among tauopathies, and there may be implications for diagnostic and therapeutic strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

GLPG1972/S201086 is a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5) inhibitor in development as an osteoarthritis disease-modifying therapy. We report the safety, tolerability, pharmacokinetics, and pharmacodynamics (turnover of plasma/serum ARGS-aggrecan neoepitope fragments [ARGS]) of GLPG1972 in 3 randomized, double-blind, placebo-controlled phase 1 trials. Study A, a first-in-human trial of single (≤2100 mg [fasted] and 300 mg [fed]) and multiple (≤1050 mg once daily [fed]; 14 days) ascending oral (solution) doses, investigated GLPG1972 in healthy men (N = 41; NCT02612246). Study B investigated multiple ascending oral (tablet) doses of GLPG1972 (≤300 mg once daily [fed]; 4 weeks) in male and female participants with osteoarthritis (N = 30; NCT03311009). Study C investigated single (Japanese: ≤1500 mg; White: 300 mg [fasted]) and multiple (Japanese, ≤1050 mg once daily; White, 300 mg once daily [fed]; 14 days) ascending oral (tablet) doses of GLPG1972 in healthy Japanese and White men (N = 88). The pharmacokinetic profile of GLPG1972 was similar between healthy participants and participants with osteoarthritis, with low to moderate interindividual variability. GLPG1972 was rapidly absorbed (median time to maximum concentration, 4 hours), and eliminated with a mean apparent terminal elimination half-life of ≈10 hours. Steady state was achieved within 2 days of dosing, with minimal accumulation. Steady-state plasma exposure after 300 mg of GLPG1972 showed no or minor differences between populations. Area under the plasma concentration-time curve (56.8-67.6 μg · h/mL) and time to maximum concentration (4 hours) were similar between studies. Urinary excretion of GLPG1972 (24 hours) was low (<11%). Multiple dosing significantly reduced ARGS levels vs baseline at all time points for all doses vs placebo. GLPG1972 was generally well tolerated at all doses., (© 2021 Galapagos NV. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Case Presentation: A 64-year-old man with a history of a 5.5-centimeter (cm) abdominal aortic aneurysm (AAA) presented to the emergency department (ED) complaining of severe back pain after climbing over a fence and falling a distance of eight feet. Prior to arrival, the prehospital paramedics reported that the patient did not have palpable pulses in either lower extremity. The initial physical examination in the ED was significant for absent dorsalis pedis pulses bilaterally as well as absent posterior tibialis pulses bilaterally and cold, insensate lower extremities. Point-of-care ultrasound identified an approximate 7-cm infrarenal AAA with a mural thrombus present. After receiving several computed tomography (CT) studies including CT head without contrast and CT angiography of the chest, abdomen and pelvis, the patient was diagnosed with acute thrombosis of AAA and associated thromboembolic occlusion of both his right and left distal iliac vessels causing bilateral acute limb ischemia. He immediately received unfractionated heparin and was admitted to the hospital for embolectomy and intra-arterial tissue plasminogen activator., Discussion: Acute thrombosis of AAA and subsequent thromboembolic events are a rare but significant complication that can occur in patients with a history of AAA. Thromboembolic events may occur spontaneously or in the setting of blunt abdominal trauma. Common presenting signs and symptoms include distal limb ischemia and absent femoral pulses. Timely management and recognition of this rare complication is vital as this condition can ultimately result in limb loss or death if not treated in a timely manner. Heparinization after confirmation of non-ruptured AAA as well as vascular surgery, and therapeutic and vascular interventional radiology consultations are key steps that should be taken to decrease patient morbidity and mortality.

Objective: Psychotherapy is the recommended first line of treatment for depression among youth; however, few youth seek professional support. This study compares barriers and facilitators to seeking psychotherapy among both youth who have and have not seen a psychotherapist. The study further explores reasons youth discontinue psychotherapy., Methods: A concurrent mixed methods study design was used. Eligible participants completed a survey (N=104) and a subset of participants completed a semi-structured interview (N=60). The survey and interview data were analyzed concurrently using a triangulation design., Results: Surveys were conducted among youth who had experienced psychotherapy (N=53) and youth who had not (N=51). The majority of participants were female. Common reasons for not seeking psychotherapy included wanting to handle their problems on their own (87.6%), thinking their problems would improve on its own (87.6%), and not knowing who to see (74.3%). Several barriers were common across the two groups, including stigma, concerns about the therapeutic relationship, and a preference for self-management. Common facilitators included improving coping skills and addressing functional impairment. There was some overlap between the barriers to seeking psychotherapy and the reasons for discontinuing, although aging out of youth-oriented service also constituted a termination factor., Conclusions: : As this study highlights the multiple factors that influence youth's psychotherapy-seeking behavior, a widespread, multi-level approach is needed to address barriers and facilitators at the individual level, but also at the community, policy, and organizational levels. Strategies such as increasing service availability and quality are needed to increase service seeking and improve retention., Competing Interests: Conflicts of Interest The authors have no financial relationships to disclose., (Copyright © 2021 Canadian Academy of Child and Adolescent Psychiatry.)

Background and Objective: Erenumab is the first migraine-specific preventive therapy approved by Health Canada since the approval of onabotulinumtoxinA 10 years ago. It is one of four calcitonin gene-related peptide antagonist monoclonal antibodies that have been commercialized worldwide for use in the headache pipeline. The objective of our study was to determine real-life efficacy of monthly erenumab for the prevention of migraine in a small case series of difficult-to-treat patients followed at a tertiary headache clinic from the Canadian province of Québec., Methods: We performed a retrospective chart audit of patients having failed four or more conventional migraine oral preventive therapies and who were treated with monthly self-administered subcutaneous erenumab (70 or 140 mg/mL dose) over a 1-year period. We assessed the patients' baseline characteristics, response to treatment, and tolerability., Results: A total of 18 patients with a diagnosis of high-frequency episodic migraines or chronic migraine met criteria (83.3% female; mean age: 48.7 years; mean duration of migraine condition: 32.9 years). Patients self-administered erenumab using a prefilled disposable autoinjector on a monthly basis; 16 patients received a 140 mg/mL dosage, two patients received a 70 mg/mL dosage. At 1 year follow-up, 50% of patients reported ≥ 50% reduction in migraine frequency and were deemed responders. Patients attempted six doses of erenumab therapy prior to discontinuation for non-response, except for two patients with other concomitant chronic pain conditions, who required ten doses to reach a 50% response. For the overall cohort, there was a decrease of 5.2 monthly migraine days; 9 days for responders and 1.3 days for non-responders (t-test (df = 16) = - 2.77, p = 0.014). There was an additional decrease of 7 monthly non-migraine days amongst patients with unremitting daily headaches; 8 days for responders and 5 days for non-responders (p > 0.05). There was a decrease of 5.4 monthly days using acute analgesics; 8.9 days for responders and 2 days for non-responders (T(16) = - 2.33, p = 0.033). The overall mean reduction in disability using the Headache Impact Test (HIT-6) score was 5.6 points; only responders showed a reduction in HIT-6 severity category (p > 0.05). The most commonly reported adverse event was constipation (16.7%), which did not lead to treatment discontinuation and was successfully managed in all patients with early counselling and intervention., Conclusion: This study supports the efficacy of erenumab in a case series of therapy-resistant migraine patients from the region of Québec. A high rate of previously failed preventive oral agents and medication overuse did not predict response in our patient cohort. In the presence of real-world complexity factors, such as psychological distress, regular opioid consumption and concomitant chronic pain conditions, a longer therapy trial may be warranted in obtaining optimal response., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Case Presentation: A 64-year-old man presented to the emergency department with a chief complaint of left shoulder pain after a mechanical fall from standing. Plain radiography revealed a displaced fracture of the inferior glenoid rim. A computed tomography further characterized the fracture and the patient was taken emergently by an orthopedic surgeon for open reduction and internal fixation., Discussion: Scapula fractures, especially isolated glenoid rim fractures, are rare and most typical of high-energy mechanism traumas. A missed or delayed diagnosis can result in long-term suffering and disability. Awareness of radiographic as well as physical findings and the subsequent classification system described below can optimize outcomes for trauma patients with glenoid fractures.

Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients. This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae , Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection. 300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection. The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF., Competing Interests: Conflict of interest: C. Marguet has nothing to disclose. Conflict of interest: V. Houdouin has nothing to disclose. Conflict of interest: I. Pin reports a presentation honorarium and travel grants from Novartis, and travel grants from AstraZeneca and AGIRadom, outside the submitted work. Conflict of interest: P. Reix has nothing to disclose. Conflict of interest: F. Huet has nothing to disclose. Conflict of interest: M. Mittaine has nothing to disclose. Conflict of interest: S. Ramel has nothing to disclose. Conflict of interest: N. Wizla-Derambure has nothing to disclose. Conflict of interest: M. Abely has nothing to disclose. Conflict of interest: M-L. Dalphin has nothing to disclose. Conflict of interest: M. Fayon has nothing to disclose. Conflict of interest: T. Bihouée reports fees for a commercial article from Vertex, personal fees for speaker bureaus from Novartis and Mylan, and travel support and registration for a congress from Teva, outside the submitted work. Conflict of interest: M. Le Bourgeois has nothing to disclose. Conflict of interest: E. Deneuville has nothing to disclose. Conflict of interest: H. Corvol has nothing to disclose. Conflict of interest: M. Laurens has nothing to disclose. Conflict of interest: L. Couderc has nothing to disclose. Conflict of interest: L. Lémée has nothing to disclose., (Copyright ©ERS 2021.)

Patients with schizophrenia (SZ) have a high level of cardiovascular morbidity and some clinical symptoms of illness remain resistant to pharmacological approaches. A large number of studies support the effectiveness of physical activity (PA) in SZ. The aims of this trial is to assess the effects of a remote, web-based adapted PA program (e-APA) compared to a health education program (e-HE) on brain plasticity in SZ and healthy volunteers (HV) and on psychiatric, neurocognitive, circadian and physical variables. The study is an interventional, multicenter, randomized open-label trial. Forty-two SZ will be randomized to either the active group (e-APA, N = 21) or nonactive group (e-HE, N = 21), and 21 HV will be matched to SZ according to age, gender, and level of PA in both e-APA and e-HE groups. Interventions will consist of 32 sessions (2 × 60 min/week, for 16 weeks) via supervised home-based videoconferencing. Cerebral magnetic resonance imaging, psychiatric symptoms, neurocognitive and circadian rhythms assessments as well as physical tests and biological analyses will be assessed at baseline and 16 weeks after the intervention. To our knowledge, this is the first study aiming to evaluate the efficacy of APA delivered by supervised home-based videoconferencing in SZ. Moreover, using multimodal MRI, this study could clarify the pathophysiological mechanisms underlying the efficacy of APA. Finally, this innovative approach might also increase participation in long-term PA since PA-based programs are known to have low adherence and early dropout. Trial registration: ClinicalTrials.gov identifier: NCT03261817. Registered on 16 August 2017.

Whether the etiology of schizophrenia remains unknown, its multifactorial aspect is conversely now well admitted. However, most preclinical models of the disease still rely on a mono-factorial construction and do not allow discover unequivocal treatments, particularly for negative and cognitive symptoms. The main interaction factors that have been implicated in schizophrenia are a genetic predisposition and unfavorable environmental factors. Here we propose a new animal model combining a genetic predisposition (1st hit: partial deletion of MAP-6 (microtubule-associated protein)) with an early postnatal stress (2nd hit: 24 h maternal separation at post-natal day 9), and a late cannabinoid exposure during adolescence (3rd hit: tetrahydrocannabinol THC from post-natal day 32 to 52; 8 mg/kg/day). The 2-hit mice displayed spatial memory deficits, decreased cortical thickness and fractional anisotropy of callosal fibers. The 3-hit mice were more severely affected as attested by supplementary deficits such a decrease in spontaneous activity, sociability-related behavior, working memory performances, an increase in anxiety-like behavior, a decrease in hippocampus volume together with impaired integrity of corpus callosum fibers (less axons, less myelin). Taken together, these results show that the new 3-hit model displays several landmarks mimicking negative and cognitive symptoms of schizophrenia, conferring a high relevance for research of new treatments. Moreover, this 3-hit model possesses a strong construct validity, which fits with gene x environment interactions hypothesis of schizophrenia. The 2-hit model, which associates maternal separation with THC exposure in wild-type mice gives a less severe phenotype, and could be useful for research on other forms of psychiatric diseases., Competing Interests: Declaration of competing interest The authors have declared that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To evaluate secondary outcomes including changes in functioning and disability associated with galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, in patients with chronic migraine., Methods: Patients randomly received galcanezumab (120 mg n = 278, 240 mg n = 277) or placebo (n = 558) during 3 months of double-blind treatment, followed by a 9-month open-label extension. The Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQv2.1) measured the impact of migraine on patient functioning. The Migraine Disability Assessment (MIDAS) quantified headache-related disability. Changes from baseline were analyzed with mixed model repeated measures or analysis of covariance., Results: Total MSQ score at baseline was 44.88 ± 18.02 (mean ± SD), indicating significant functional impairment. At Month 3, least squares (LS) mean change ± SE in total MSQ for galcanezumab-treated patients were 20.51 ± 1.49 (120 mg) and 20.49 ± 1.49 (240 mg), both statistically significantly greater vs placebo-treated patients (14.55 ± 1.21; both P < 0.001). Total MIDAS score at baseline was 67.24 ± 57.31 (mean ± SD). At Month 3, LS mean change ± SE from baseline in total MIDAS for galcanezumab-treated patients was statistically significantly greater than placebo for 120 mg group (placebo: - 11.53 ± 3.38 vs 120 mg: - 20.27 ± 4.07; P < 0.05) but not for 240 mg group (- 17.02 ± 4.05). At Month 12, within-group mean changes from baseline for total MSQ (28.56 ± 1.19 previous placebo; 29.53 ± 1.51 previous 120 mg; 25.83 ± 1.49 previous 240 mg) and MIDAS scores (- 28.47 ± 2.95 previous placebo; - 31.47 ± 3.69 previous 120 mg; - 31.13 ± 3.62 previous 240 mg) were statistically significant (P < 0.001) for the open-label treatment population regardless of previous double-blind treatment assignment., Conclusions: Galcanezumab-treated patients with chronic migraine reported statistically significant improvements in functioning and disability, representing a clinically significant change., Trial Registration: ClinicalTrials.gov registry: NCT02614261. Registered 25 November 2015.

Introduction: Use of triptans for acute treatment of migraine is associated with insufficient efficacy and/or tolerability in approximately 30-40% of people. We conducted a systematic literature review (SLR) to synthesize definitions, terminology, subsequent treatment outcomes, and characteristics associated with this subpopulation., Methods: A comprehensive SLR was conducted to identify studies, published from Jan 1995 to May 2019, which focused on insufficient efficacy and/or tolerability to triptans., Results: Thirty-five publications were identified, of which 22 described randomized controlled trials and open-label studies, and 13 described observational studies. Across studies, multiple objectives and a high amount of variability in methodologies and outcomes were noted. The most commonly applied measures of efficacy were headache pain freedom and pain relief at 2 h. Ten studies assessed efficacy of switching or optimizing treatment in patients with historical insufficient efficacy or tolerability to previous triptan treatment and demonstrated varying levels of success. Factors associated with increased risk of triptan insufficient efficacy included severe baseline headache severity, photophobia, phonophobia, nausea, and depression., Conclusions: Irrespective of the methodology or definition used to identify people with insufficient efficacy and/or tolerability to triptans, study results support the assertion that a high unmet need remains for effective acute treatment of migraine.

NonInvasive Brain Stimulation (NIBS) is a potential therapeutic tool with growing interest, but neuronavigation-guided software and tools available for the target determination are mostly either expensive or closed proprietary applications. To address these limitations, we propose GeodesicSlicer, a customizable, free, and open-source NIBS therapy research toolkit. GeodesicSlicer is implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. GeodesicSlicer uses cortical stimulation target from either functional or anatomical images to provide functionality specifically designed for NIBS therapy research. The provided algorithms are tested and they are accessible through a convenient graphical user interface. Modules have been created for NIBS target determination according to the position of the electrodes in the 10-20 system electroencephalogram and calculating correction factors to adjust the repetitive Transcranial Magnetic Stimulation (rTMS) dose for the treatment. Two illustrative examples are processing with the module. This new open-source software has been developed for NIBS therapy: GeodesicSlicer is an alternative for laboratories that do not have access to neuronavigation system. The triangulation-based MRI-guided method presented here provides a reproducible and inexpensive way to position the TMS coil that may be used without the use of a neuronavigation system.

Purpose: Applications of deep learning to histopathology have proven capable of expert-level performance, but approaches have largely focused on supervised classification tasks requiring context-specific training and deployment. More generalizable workflows that can be easily shared across subspecialties could help accelerate and broaden adoption. Here, we hypothesized that histology-optimized feature representations, generated by a convolutional neural network (CNN) during supervised learning, are transferable and can resolve meaningful differences in large-scale, discovery-type unsupervised analyses., Methods: We used a CNN, previously trained to recognize brain tumor histomorphologies, to extract 512 feature representations from > 550 digital whole-slide images (WSIs) of renal cell carcinomas (RCCs) from The Cancer Genome Atlas and other previously unencountered tumors. We use these extracted feature vectors to conduct unsupervised image-set clustering and analyze the clinical and biologic relevance of the intra- and interpatient subgroups generated., Results: Within individual WSIs, feature-based clustering could reliably segment tumor regions and other relevant histopathologic subpatterns (eg, adenosquamous and poorly differentiated regions). Across the larger RCC cohorts, clustering extracted features generated subgroups enriched for clinically relevant subtypes (eg, papillary RCC) and outcomes (eg, survival). Importantly, individual feature activation mapping highlighted salient subtype-specific patterns and features of malignancies (eg, nuclear grade, sarcomatous change) contributing to subgroupings. Moreover, some proposed clusters were enriched for recurring, human-based RCC-subtype misclassifications., Conclusion: Our data support that CNNs, pretrained on large histologic datasets, can extend learned representations to novel scenarios and resolve clinically relevant intra- and interpatient tissue-pattern differences without explicit instruction or additional optimization. Repositioning of existing histology-educated networks could provide scalable approaches for image classification, quality assurance, and discovery of unappreciated patterns and subgroups of disease.

In 2017, the International Headache Society convened a Global Patient Advocacy Summit (GPAS-1) to begin a collaborative effort involving patients, patient advocates, patient advocacy organizations, healthcare professionals, scientists, professional pain, neurology, and headache societies, pharmaceutical manufacturers, and regulatory agencies to advance issues of importance to patients affected by headache worldwide. In September 2019, the second Global Patient Advocacy Summit (GPAS-2) was convened to revisit issues from the inaugural meeting, assess the progress of the International Headache Society Global Patient Advocacy Coalition (IHS-GPAC) in meeting the goals set forth therein, and discuss strategies for achieving established goals and supporting future development. Short- and long-term mandates from the first Summit were realized, including publishing the Vancouver Declaration on Global Headache Patient Advocacy 2018, determining the governing and operational structures of the IHS-GPAC, and helping to facilitate the first World Federation of Neurology World Brain Day dedicated to migraine. Another short-term mandate, creating a unified advocacy strategy, was fulfilled by the Coalition's decision to focus on encouraging support from employers and implementing employee support programs for people with migraine. To help execute the strategy, the Coalition is developing an employer engagement toolkit that will educate employers and employees about the impact of migraine in the workplace, reduce stigma directed toward employees with migraine, and facilitate the care of employees with migraine to reduce the burden of illness and improve workplace productivity. Coalition members will disseminate the toolkit and encourage the adoption of migraine workplace programs by employers worldwide. The Coalition has established an alliance with two global, multinational employers to expand migraine awareness and support among policy makers and other stakeholders around the world. The IHS-GPAC met many of the goals established at GPAS-1, and it has initiated a global strategy focused on the psychosocial and economic toll of headache disorders, especially migraine, in the workplace. Ongoing and future activities will explore a range of opportunities with employers and across the full spectrum of advocacy goals.

Objective: In healthy individuals, the visuospatial attentional network consists of frontoparietal bundles; however, the anatomical organization of this network in persons with schizophrenia remains largely unknown. Using diffusion tensor imaging-based tractography, the authors investigated the white matter integrity and volume of frontoparietal and frontotemporo-occipital bundles in the right and left hemispheres and studied their structural asymmetry in persons with schizophrenia and in healthy individuals., Methods: This study included 34 participants with schizophrenia and 69 healthy individuals. Integrity parameters and volume were calculated in the three branches of the superior longitudinal fasciculus (SLF I, II, and III), the inferior longitudinal fasciculus, and the inferior fronto-occipital fasciculus in both hemispheres., Results: In the SLF II and SLF III of the right hemisphere, healthy individuals showed greater integrity, compared with participants with schizophrenia. Both groups presented increased integrity in the SLF III of the right hemisphere, compared with the SLF III of the left hemisphere, but only healthy individuals had this pattern regarding the SLF II. Bundle volumes did not differ between groups., Conclusions: This study is the first to describe the structural hemispheric lateralization and organization of the visuospatial attentional network in persons with schizophrenia. The main findings indicate loss of integrity in the SLF II, associated with loss of asymmetry in participants with schizophrenia, compared with healthy individuals, suggesting a potential substrate of attentional deficits.

Corpus callosum (CC) volume and surface (macrostructural) studies remain controversial and have not considered the illness duration (ID) systematically. Regardless of ID, some CC macrostructural studies have shown no difference between SZ patients and healthy controls (HC), whereas others have reported macrostructural abnormalities in SZ. Conversely, CC microstructural studies are more in agreement with alterations in CC integrity regardless of the patients' ID, but the direction and degree of these abnormalities over time remain unknown. Moreover, no study has explored both the micro- and macrostructure of the CC in SZ by considering the stage of disease. Both CC micro- and macrostructural data were investigated in 43 SZ patients and compared between two patient groups (21 patients with a short ID and 22 with a long ID) and HC (23 participants) using diffusion tensor and structural imaging. CC microstructural alterations were detected in both SZ groups compared to the HC group, without differences between the SZ groups. In contrast, CC macrostructural alterations were only found in the long ID group. CC microstructural alterations might be detected in schizophrenia at an early stage, without an increase of magnitude thereafter, while CC macrostructural alterations might become apparent at later stages of the illness., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To evaluate changes from baseline in patient-reported outcomes for measures of functioning and disability among patients with migraine treated with galcanezumab or placebo., Methods: Patients with episodic migraine (4-14 monthly migraine headache days) were treated with either galcanezumab (Evaluation of LY2951742 in the Prevention of Episodic Migraine [EVOLVE]-1: 120 mg n = 210, 240 mg n = 208; EVOLVE-2: 120 mg n = 226, 240 mg n = 220) or placebo (EVOLVE-1 n = 425; EVOLVE-2 n = 450) during 6 months of treatment. Migraine-Specific Quality of Life Questionnaire v2.1 (MSQv2.1) measured the effect of migraine on patient functioning (physical and emotional) in 3 domains, and the Migraine Disability Assessment (MIDAS) quantified headache-related disability associated with missed or reduced productivity at work or home and social events. Both were collected at baseline and during the treatment period (MSQv2.1 = monthly; MIDAS = months 3 and 6 only)., Results: Differences in MSQv2.1 total score least squares (LS) mean change from baseline (month 4-6) for galcanezumab (120 and 240 mg, respectively) were superior to placebo (EVOLVE-1 = 7.3 and 6.7 [both p < 0.001]; EVOLVE-2 = 8.5 and 7.3 [both p < 0.001]). Differences were similar for all domain scores ( p < 0.001 for both galcanezumab doses compared with placebo), were observed as early as month 1, and were sustained for 6 months for most domains. Differences of MIDAS LS mean change from baseline (month 6) for galcanezumab (120 and 240 mg, respectively) compared with placebo were: EVOLVE-1 = -6.3 ( p < 0.001) and -5.2 ( p = 0.002); EVOLVE-2 = -9.2 and -8.2 (both p < 0.001)., Conclusions: Patients with episodic migraine treated with galcanezumab reported significant and clinically meaningful improvements in daily functioning and decreased disability compared with patients who received placebo., Classification of Evidence: This study provides Class II evidence that for patients with migraine, galcanezumab (120 mg or 240 mg) given once monthly improved functioning and reduced disability., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose of Review: Heterotopic ossification (HO) in hip arthroscopy is a common post-operative complication. This review was undertaken to provide an update (2014 present) on the current literature regarding HO in hip arthroscopy., Recent Findings: Risk factors for HO post-hip arthroscopy include male gender, mixed impingement, picture, and the size of CAM resection. HO prophylaxis with NSAIDs has been proven to decrease the rate of HO post-hip arthroscopy; however, there is inherent risk to long-standing NSAIDs therapy. HO post-hip arthroscopy is not uncommon as a radiological finding, but symptomatic HO post-hip arthroscopy requiring revision surgery is a rare event, at < 1%. The outcomes for revision surgery for HO excision have fair outcomes. The hip arthroscopist should stratify their patients based on known risk factors, and determine whether NSAIDs prophylaxis is warranted.

Neuroimaging studies have revealed brain regions involved in social cognition, which reportedly show functional alterations in schizophrenia. However, the social neural network has not been investigated with regards to language perception and social interactions in daily life. Here we developed and validated an integrative fMRI task to explore the neural basis of social cognition with regards to language perception in schizophrenia. The task comprised listening to film extracts and inferring mental states to characters. We first identified the functional network activated during the task in 28 healthy controls (HC). Next, we evaluated the reproducibility of Blood-Oxygen-Level Dependent (BOLD) variations in 14 HC participants. Finally, we investigated network impairment in 20 patients with schizophrenia (SZ) compared to HC. The HC group exhibited bilateral activation in the superior and middle temporal gyri (including the poles and the temporo-parietal junction). Overall, our novel integrative task induced activation of a functional network with good reproducibility and involved in language conveying social information. Compared to the HC group, the SZ group showed decreased recruitment of the right temporo-parietal junction. These findings may be useful for testing the impact of remediation on the brain, particularly on the network of language conveying social information., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: The present study aimed to assess the influence of dental occlusion on body posture and the competitive performance of young elite rowers., Method: Dental occlusion disturbance devices were used to simulate dental malocclusions. We assessed the influence of malocclusion on the body balance, paravertebral muscle contraction symmetry, and muscular power of young elite rowers. A nonparametric permutation test for repeated measures ANOVA, a Cochran's Q test for paired data and a paired Student's t-test were used in order to statistically evaluate the influence of artificial occlusal disturbance on each factor. A force platform and a Dyno Concept 2 machine were used as measuring instruments., Results: A total of 7 members of the "Pôle France Aviron" (age range of 15-17 years) were enrolled in the study. None of the body balance parameters was significantly influenced by the artificial occlusal disturbance. The interposition of an occlusal silicone splint significantly increased the proportion of athletes presenting asymmetric muscular contractions from 14.3% to 85.7% (p=0.025) and induced a significant 17.7% decrease in the athletes' muscular power (p=0.030)., Conclusions: This study shows the negative impacts of an occlusal disturbance on the athletic performance of young elite rowers. The detection of malocclusion traits by regular occlusal monitoring would be of great interest in this population.

Long-latency auditory event potentials (LLAEPs) involving local and global auditory processes have been investigated to examine the impact of low-frequency (LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of the temporal cortex. We hypothesized that both stimulation frequencies have the same modulation effect, in accordance with clinical data showing a reduction in auditory verbal hallucinations (AVHs) after LF and HF temporal rTMS in patients with schizophrenia. With 30 right-handed healthy volunteer participants enrolled in a crossover trial, we analyzed LLAEPs before and after LF- and HF-rTMS of the left temporal cortex. While we observed no changes in latencies, we did observe a similar inhibitory action of both rTMS frequencies on LLAEP amplitudes. Analysis of surface potential maps and cortical generators revealed some differences regarding auditory processes: HF-rTMS produced earlier, more diffuse, and more right-lateralized effects than LF-rTMS. Beyond a local impact, rTMS exerted a remote modulation influence on the frontal cortex that might be involved in attentional processes. This association could explain the therapeutic effect of temporal HF-rTMS on AVH., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The fronto-striato-thalamic circuitry is a key network in patients with schizophrenia (SZPs). We use diffusion tensor imaging (DTI) to investigate the integrity of white matter (WM) pathways involved in this network in SZPs relative to healthy controls (HCs). We also evaluate the differential impact of chronic exposure to clozapine as well as other atypical and typical antipsychotics. 63 HCs and 41 SZPs were included. Of the SZPs, 16 were treated with clozapine (SZPsC), 17 with atypical antipsychotics (SZPsA), and 8 with typical antipsychotics (SZPsT). Three tracts were reconstructed in the left hemisphere using tractography: one fronto-subcortical tract, one prefronto-subcortical tract, and one prefronto-frontal tract. Diffusion parameters were individually extracted in each tract. SZPs exhibited lower integrity in both the fronto-subcortical and prefronto-subcortical tracts relative to HCs, and SZPsT showed altered integrity compared to SZPsC. There were no WM integrity differences in the prefronto-frontal tract between SZP groups or between SZPs and HCs. SZPs exhibit structural connectivity abnormalities in the prefronto-fronto-subcortical network that are specifically and differentially impacted by the type of antipsychotic treatment. Additional studies are needed to separate the contributions of clozapine-mediated neuroprotection, neurotoxicity related to typical antipsychotics, and the illness itself to observed differences., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation., Methods: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS)., Results: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14., Discussion: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

Background: Occipital nerve stimulation (ONS) has been used for the treatment of neuropathic pain conditions and could be a therapeutic approach for refractory cervicogenic headache (CeH)., Aim: The aim of this study is to assess the efficacy and safety of unilateral ONS in patients suffering from refractory CeH., Methods: We conducted a retrospective chart review on patients implanted from 2011 to 2013 at CHUM. The primary outcome was a 50% reduction in headache days per month. Secondary outcomes included change in EuroQol Group Visual Analog Scale rating of health-related quality of life (EQ VAS), six item headache impact test (HIT-6) score, hospital anxiety and depression scale (HADS) score, work status, and medication overuse., Results: Sixteen patients fulfilled the inclusion criteria; they had suffered from daily moderate to severe CeH for a median of 15 years. At one year follow-up, 11 patients were responders (69%). There was a statistically significant improvement in the EQ VAS score (median change: 40 point increase, p = 0.0013) and HIT-6 score (median change: 17.5 point decrease, p = 0.0005). Clinically significant anxiety and depression scores both resolved amongst 60% of patients. At three years, six patients were responders (37.5%). Out of the 11 responders at one-year post implantation, five had remained headache responders (R-R) and one additional patient became a responder (NR-R). There was a statistically significant improvement in the EQ VAS score (median change: 15 point increase, p = 0.019) and HIT-6 score (median change: 7.5 point decrease, p = 0.0017) compared with baseline. Clinically significant anxiety and depression scores both, respectively, resolved among 22.5% and 33.9% of patients. Five out of seven disabled patients were back to work., Conclusion: ONS may be a safe and effective treatment modality for patients suffering from a refractory CeH. Further study may be warranted., (© 2017 International Neuromodulation Society.)

Objectives: To compare the impact of a combined nursing and medical approach to a medical follow-up only on headache outcomes, quality of life, and self-efficacy in a cohort of migraineurs., Background: Interdisciplinary approaches have been proposed for migraine management. A nursing intervention could improve patient outcomes., Methods: We prospectively studied new patients referred to our tertiary headache center for migraine. The control group was followed by a physician; the active group was also followed by a nurse with a personalized intervention including adaptation of the lifestyle., Results: Two hundred patients (176 women and 24 men, mean age 40 years old) were included and classified according to headache frequency. Each group was followed for 12 months with daily headache diaries. One hundred and sixty-two completed the study. There were no significant differences between groups for the decrease in headache days, the percent of chronic patients reverting to episodic status or the cessation of medication overuse. Patients in the control group were more likely to find a successful prophylaxis (55.6 vs 27.7%, P = .002). Despite this, the mean decrease in HIT-6 scores at month 8 was 5.23 ± 9.18 for the active group compared with a decrease of 2.10 ± 9.27 for the control group (P = .030, clinically significant difference of 3.13). Headache Management Self-Efficacy Scale (HMSE) scores, representing the feeling of self-efficacy, increased by 14.35 ± 18.41 for the active group vs 4.69 ± 21.22 in the control group (P = .002)., Conclusion: A nursing intervention can lower the impact of migraines on the patient's life. The improvement in the HIT-6 score in this study was correlated with improvements in self-efficacy., (© 2017 American Headache Society.)

Objectives: Impairments in language production are common of schizophrenia (SZ) and bipolar disorder (BD). Identifying distinct functional connectivity (FC) patterns in SZ and BD may provide biomarkers for their diagnoses., Methods: Forty-nine participants (15 SZ, 14 BD and 20 healthy controls (HC)) underwent a verbal fluency task consisting of mentally generating verbs in French, alternated with periods of silence. Functional network allowed identifying activation clusters: the medio-frontal cluster (MFC), the left subcortical cluster (LSCC) and the left fronto-lateral cluster (LFLC). FC was calculated between the average blood oxygen level-dependent signal time series in each cluster. Analyses of covariance were performed to test group differences on FC among the three paired-seed regions., Results: SZ presented a significant reduced FC compared to HC within two paired-seed regions between the LFLC and the LSCC and between the MFC and the LSCC while BD were not significantly different from HC. SZ compared to BD exhibited a reduced FC within one paired-seed region between the MFC and the LSCC. There was no group effect between the MFC and the LFLC., Conclusions: A specific medio-prefronto-striato-thalamic functional dysconnectivity may be implicated in the pathophysiology of schizophrenia. This reduced fronto-subcortical FC could be a functional brain biomarker of schizophrenia.

This exploratory study investigated the functional connectivity (FC) in the language network in schizophrenia patients (SZ) with auditory verbal hallucinations (AVHs), and the therapeutic efficacy of rTMS on it. Eleven SZ with AVHs and 10 healthy controls (HC) underwent two fMRI sessions using a speech listening paradigm. SZ received 20Hz rTMS following the first fMRI session. Compared to HC, SZ showed a reduced FC in the language network. While AVHs improved after 12days, no changes in FC were observed. This suggests the efficacy of high-frequency rTMS on AVH without any impact for rTMS on FC within the language network., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pedophilia refers to the recurrent, intense sexual interest in prepubescent children who, by definition, have not developed any secondary sex characteristics. Researchers have begun to investigate whether persons with pedophilia are qualitatively different from those without pedophilia (pedophilia is a taxon) or if people vary in their level of sexual interest toward children (pedophilia is dimensional). Two relatively small studies have previously attempted to address this question, but produced conflicting results. The present study built on these studies with a substantially larger sample of 2,227 men who committed sexual offenses and were assessed at a sexual behavior clinic. The present study also examined a broader range of measures more closely approximating the diagnostic criteria for pedophilic disorder, including phallometric assessment of sexual arousal patterns. The results of 3 taxometric analyses did not find support for the assertion that pedophilia is a taxon. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)