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Satoshi Asakura,1 Taiji Hayano,2 Atsushi Hagino,2 Tsukasa Koyama3 1Health Care Center and Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 2Clinical Development Planning and Management, Mochida Pharmaceutical Co., Ltd, Tokyo, 3Clinical Research Center, Oyachi Hospital, Sapporo, Hokkaido, Japan Purpose: To investigate the safety, tolerability, and effectiveness of escitalopram in patients with social anxiety disorder in Japan.Methods: A 52-week, open-label study was conducted in Japanese patients with social anxiety disorder with a total score ≥60 on the Liebowitz Social Anxiety Scale – Japanese Version (LSAS-J) and ≥4 on the Clinical Global Impression – Severity Scale. Escitalopram 10 mg/day was administered for the first week and could be increased to 20 mg/day.Results: The study included 158 patients: 81.0% (128/158) completed 52 weeks of escitalopram treatment, 68.4% (108/158) increased their dose to 20 mg/day, and 56.3% (89/158) remained on 20 mg/day. Adverse drug reactions were reported by 57.6% (91/158) of patients. The most common (incidence ≥10%) were somnolence and nausea. The incidence of adverse drug reactions was similar in extensive and poor metabolizers of cytochrome P450 2C19. No adverse drug reactions increased in incidence by >5% after week 12. The incidence of serious adverse events was 1.3% (2/158). No deaths occurred. The LSAS-J total scores improved until week 52. The LSAS-J response rate (≥30% improvement in LSAS-J) was 69.0%, the Clinical Global Impression – Improvement Scale response rate (≤2) was 73.0%, and the LSAS-J remission rate (≤30) was 27.0%.Conclusion: In this first 52-week clinical study of social anxiety disorder, escitalopram 10–20 mg/day was safe, well tolerated, and effective in Japanese patients. Keywords: escitalopram, Japanese, long-term study, social anxiety disorder, selective serotonin reuptake inhibitors

We investigated the oncogenic role of SETDB1, focusing on non-small cell lung cancer (NSCLC), which has high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry; 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p

We report a rare case of Churg-Strauss syndrome (CSS) in a 41-year-old Japanese man with a history of middle-age onset of bronchial asthma who had severe abdominal pain. He presented with ileus caused by an annular ulcer of the ileum, attributable to mucosal ischemia resulting from necrotizing vasculitis of the mesenteric artery. He also had marked hypereosinophilia (51.5%), elevated serum IgE levels (34040 IU/ml), and generalized enlargement of the superficial cervical lymph nodes, containing eosinophilic granulomas. A stenotic lesion caused by an annular ulcer in the ileum was found and resected by laparotomy. Microscopic examination of the resected specimen revealed luminal narrowing or occlusion of small arteries in the ulcer base, subserosa, and mesenterium resulting from marked fibrotic intimal thickening with fragmentation or lack of the internal elastic lamina. These findings were diagnosed as vasculitis, scar stage. The postoperative course was uneventful, with the patient receiving a maintenance dose of prednisolone (10-15 mg/day) for 7 years subsequently. We must carefully diagnose and treat patients with middle-age onset asthma, because the symptom may be a lung manifestation of CSS, in which various organs including gastrointestinal tract are involved as a result of systemic necrotizing vasculitis. [ABSTRACT FROM AUTHOR]

We treated two rare cases of acute rhabdomyolysis induced by heat stroke encountered during mountaineering. The clinical findings were complicated by severe acute renal failure and disseminated intravascular coagulation (DIC), respectively. Though heat-related disorders occur frequently in mountain medicine in summer, severe and fatal rhabdomyolysis due to heat stroke is rare. It was also noteworthy that both patients had received treatment with antipsychotic drugs including phenothiazine. Even in a moderate exercise activity such as mountaineering, the possibility of rhabdomyolysis should be considered for all cases of heat stroke, especially those with a history of antipsychotic neuroleptics. [ABSTRACT FROM AUTHOR]

Abstract: This study examines the challenges and accommodations for medical residents with disabilities within physical medicine and rehabilitation training programs. Medical residency presents unique stressors and responsibilities, with the potential for added complexities for residents with disabilities. Few data exist regarding the prevalence and experiences of people with disabilities as medical trainees and the limited studies available highlight an underrepresentation of individuals with disability in medical training and practice. Through cross-sectional surveys administered to physical medicine and rehabilitation residents, this research assesses disability prevalence, characterizations, barriers to training, and accommodations provided. Of 140 respondents, 9.3% identified as having disabilities, with varying prevalence among genders and disability types. Results revealed distinct challenges for residents with mobility and nonmobility disabilities, spanning learning environments, standardized testing, procedural skills, and accessibility. Self-provided accommodations exceeded program-provided ones, indicating room for improvement in program support. These findings underscore the need for proactive dialog between residents and leadership to address barriers, enhance accommodations, and create an inclusive training environment. The study's insights emphasize the importance of advocating for equal opportunities and cultivating supportive conditions to enable individuals with disabilities to thrive in medical residency programs, ultimately contributing to more diverse and inclusive medical communities., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b ∆iThy mice) develop chronic inflammation. Bcl11b ∆iThy mice lack conventional T cells and MAIT cells, whereas CD4 + IL-18R + αβ T cells expressing skewed Traj33 (Jα33) + T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b ∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33 + T cells expanded in Bcl11b ∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential., (© 2022. The Author(s).)

Currently, proteins equipped with "ribosomal arrest peptides" (RAPs) that regulate the expression of downstream genes and their own activity by pausing their own translation during elongation are extensively studied. However, studies focusing on RAP have been conducted primarily in prokaryotic cells; studies on eukaryotic cells, especially mammalian cells, are limited. In the present study, we comprehensively examined translationally arrested nascent polypeptides to gain novel insights into RAPs in mammalian cells. Cetyltrimethylammonium bromide was used to obtain nascent polypeptide chains that were translationally arrested during translation elongation. After proteomic analysis, additional screening by discriminating according to amino acid residues at the C-terminal end revealed several novel RAP candidates. Our method can be applied for comprehensive RAP studies in mammalian cells., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Brown adipose tissue (BAT) has a role in maintaining systemic metabolic health in rodents and humans. Here, we show that metabolic stress induces BAT to produce coagulation factors, which then-together with molecules derived from the circulation-promote BAT dysfunction and systemic glucose intolerance. When mice were fed a high-fat diet (HFD), the levels of tissue factor, coagulation Factor VII (FVII), activated coagulation Factor X (FXa), and protease-activated receptor 1 (PAR1) expression increased significantly in BAT. Genetic or pharmacological suppression of coagulation factor-PAR1 signaling in BAT ameliorated its whitening and improved thermogenic response and systemic glucose intolerance in mice with dietary obesity. Conversely, the activation of coagulation factor-PAR1 signaling in BAT caused mitochondrial dysfunction in brown adipocytes and systemic glucose intolerance in mice fed normal chow. These results indicate that BAT produces endogenous coagulation factors that mediate pleiotropic effects via PAR1 signaling under metabolic stress., Competing Interests: The authors except for T.M. disclose no conflicts of interest. T.M. discloses the joint research funds and the remuneration for a lecture from Bayer; however, this company did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the article., (© 2022 The Author(s).)

Retinitis pigmentosa (RP) and macular dystrophy (MD) are characterized by gradual photoreceptor death in the retina and are often associated with genetic mutations, including those in the prominin-1 (Prom1) gene. Prom1-knockout (KO) mice recapitulate key features of these diseases including light-dependent retinal degeneration and constriction of retinal blood vessels. The mechanisms underlying such degeneration have remained unclear, however. We here analysed early events associated with retinal degeneration in Prom1-KO mice. We found that photoreceptor cell death and glial cell activation occur between 2 and 3 weeks after birth. Whereas gene expression was not affected at 2 weeks, the expression of several genes was altered at 3 weeks in the Prom1-KO retina, with the expression of that for endothelin-2 (Edn2) being markedly upregulated. Expression of Edn2 was also induced by light stimulation in Prom1-KO mice reared in the dark. Treatment with endothelin receptor antagonists attenuated photoreceptor cell death, gliosis and retinal vessel stenosis in Prom1-KO mice. Our findings thus reveal early manifestations of retinal degeneration in a model of RP/MD and suggest potential therapeutic agents for these diseases. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

The mammalian cell nucleus is a highly organized organelle that contains membrane-less structures referred to as nuclear bodies (NBs). Some NBs carry specific RNA types that play architectural roles in their formation. Here, we show two types of RNase-sensitive DBC1-containing NBs, DBC1 nuclear body (DNB) in HCT116 cells and Sam68 nuclear body (SNB) in HeLa cells, that exhibit phase-separated features and are constructed using RNA polymerase I or II transcripts in a cell type-specific manner. We identified additional protein components present in DNB by immunoprecipitation-mass spectrometry, some of which (DBC1 and heterogeneous nuclear ribonucleoprotein L [HNRNPL]) are required for DNB formation. The rescue experiment using the truncated HNRNPL mutants revealed that two RNA-binding domains and intrinsically disordered regions of HNRNPL play significant roles in DNB formation. All these domains of HNRNPL promote in vitro droplet formation, suggesting the need for multivalent interactions between HNRNPL and RNA as well as proteins in DNB formation.

Background: The loadrate of the vertical ground reaction force at impact has been associated with a variety of running injuries. Peak tibial shocks occur during the early stance phase and has been shown to be correlated to the loadrates in healthy runners using a rearfoot strike pattern. As a result, tibial accelerometry has been used as a surrogate for loadrates. However, these correlations have not been assessed in injured runners nor in runners with differing footstrike patterns., Objective: To examine the relationship between tibial acceleration and loadrates in injured runners who are habitual rearfoot (RFS), midfoot (MFS), and forefoot (FFS) strikers. Tibial acceleration was expected to be positively associated with loadrates across all footstrike patterns., Design: Cross-sectional cohort., Setting: Academic medical center with biomechanics laboratory., Participants: One hundred sixty-nine injured runners (age 38.7 ± 13.1 years, 127 RFS, 17 MFS, 25 FFS)., Methods: Each participant completed a biomechanical assessment for injury including evaluation on a force treadmill with a triaxial accelerometer fastened by a Velcro strap to the distal medial tibia. Peak vertical and resultant tibial acceleration (VTA, RTA) were measured from the accelerometer. Vertical average and instantaneous loadrates (VALR, VILR) and the resultant instantaneous loadrate (RILR) were determined from the force data., Main Outcome Measurements: The relationship between tibial acceleration and loadrates measured using Pearson's correlation coefficient (r)., Results: Loadrates were each associated with VTA (r = 0.66-0.82, P < .001) and RTA (r = 0.41-0.68, P < .05) across all footstrike groups with the exception of association of VILR to RTA in the FFS group. The strength in correlations was lowest between RTA and loadrates for the FFS runners (r = 0.41-0.47, P < .05)., Conclusion: Vertical tibial acceleration is the stronger surrogate for loadrates in injured runners across differing footstrike patterns., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

Background: Studies have revealed a higher incidence of injury and illness among elite adaptive athletes when compared to able-bodied athletes in competition. However, individuals with disabilities report poorer access to health care., Objective: The purpose of this study is to identify differences in healthcare access, satisfaction, and unmet needs between recreational adaptive and able-bodied athletes in all sports and within a single sport (hockey)., Design: Cross-sectional, survey-based study., Setting: Recreation sports programs in Boston, MA and Chicago, IL., Participants: Adult, recreational, competitive adaptive, and able-bodied athletes., Interventions: Not applicable., Main Outcome Measure(s): The Short-Form Patient Satisfaction Questionnaire (PSQ-18) for healthcare access and satisfaction; percentage of athletes reporting unmet sports-related healthcare needs in the prior year., Results: Sixty adaptive athletes (78% male, age 35.7 ± 12.4 years) and 65 able-bodied athletes (40% male, age 34.9 ± 11.9 years) participated. Mean access and satisfaction scores were not significantly different between groups in all sports (P = .53 and P = .19, respectively) or hockey (P = .28 and P = .55, respectively). Unmet needs were more commonly reported among adaptive athletes (18.3% all sports, 20.0% hockey) as compared to able-bodied athletes (9.2% all sports, 4.0% hockey). This reached statistical significance in the hockey group (P = .03), but not all sports (P = .12)., Conclusions: No differences were seen between groups in healthcare access or satisfaction scores. Adaptive athletes of the same sport reported a higher rate of unmet sports-related healthcare needs but with few doctor's visits in the preceding year, suggesting discrepancies in expectations and healthcare-seeking behavior., Level of Evidence: III., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

Activation of ribosomal RNA (rRNA) synthesis is pivotal during cell growth and proliferation, but its aberrant upregulation may promote tumorigenesis. Here, we demonstrate that the candidate oncoprotein, LYAR, enhances ribosomal DNA (rDNA) transcription. Our data reveal that LYAR binds the histone-associated protein BRD2 without involvement of acetyl-lysine-binding bromodomains and recruits BRD2 to the rDNA promoter and transcribed regions via association with upstream binding factor. We show that BRD2 is required for the recruitment of the MYST-type acetyltransferase KAT7 to rDNA loci, resulting in enhanced local acetylation of histone H4. In addition, LYAR binds a complex of BRD4 and KAT7, which is then recruited to rDNA independently of the BRD2-KAT7 complex to accelerate the local acetylation of both H4 and H3. BRD2 also helps recruit BRD4 to rDNA. By contrast, LYAR has no effect on rDNA methylation or the binding of RNA polymerase I subunits to rDNA. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Bibliometrics use statistical methods to measure the scholarly impact of publications. Bibliometrics are categorized as conventional metrics or alternative metrics. Conventional metrics have often been considered the standard to measure the impact of publication-related scholarship. With the growing popularity of social media and ease of instantaneous distribution of information globally, alternative metrics have become an important complementary measure of scholarly activity. Bibliometrics may provide a standard performance measurement that may be used for tenure and/or promotion among academic institutions. The alternative metric industry has shown considerable growth with increasingly improved algorithms working towards standardization. Together, conventional metrics and alternative metrics may synergistically complement each other to provide an accelerated translation from research to clinical care that may lead to tremendous benefits in patients. All physicians and other healthcare professionals should receive training in bibliometrics and understand the potential impact of professional social media use.

This is a case of a 19-year-old female collegiate field hockey player with left leg pain, numbness, and tingling. A comprehensive workup including dynamic ultrasound, magnetic resonance imaging (MRI), and magnetic resonance angiogram (MRA) revealed a type VI functional popliteal artery entrapment syndrome (PAES). There are many options for treatment of functional PAES including activity modification, botulinum toxin injection, and surgery. To the authors' knowledge there is no published return to sport recommendation for postsurgical functional PAES. This report highlights alternative treatment options and proposes a postsurgical return to play rehabilitation protocol in functional PAES. LEVEL OF EVIDENCE: V., (© 2018 American Academy of Physical Medicine and Rehabilitation.)

Regenerative medicine has shown dramatic expanse and evolution in the past decade. Within that milieu, physiatrists are taking an active role in research, clinical care delivery, and education. The purpose of this review is to provide a balance among evidence, theory, experience, clinical trends, and the foreseeable future. We focus on the literature that reports the research with the best methodology in each practice area, recognizing that the level of evidence varies substantially among different treatment modalities and conditions. The following elements are included: an overview of the evolution of currently available regenerative techniques, evidence base for each available modality (prolotherapy, platelet rich plasma, bone marrow aspirate concentrate and stem cells, adipose-derived stem cells, and amniotic tissue products), general principles in the application of these treatments, and discussion and a vision of what lies ahead. We expect that practitioners will use this review to facilitate clinical decision making and to provide a core knowledge base to assist when counseling patients. LEVEL OF EVIDENCE: IV., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Recent studies have shown that long non-coding RNAs (lncRNAs) have key functions during breast cancer development. Considering the complexity of IncRNAs regulatory network, the identification of novel and functional lncRNAs associated with breast cancer is thus very important. By using Agilent LncRNA Human Gene Expression Microarray, we identified a number of lncRNAs that were differentially expressed in breast cancer compared to their corresponding adjacent tissues. According to the microarray, the expression of p10247, henceforth named as lncRNA-BCHE (standing for lncRNA high expressed in breast cancer), was found to be uniformly higher in all the five breast cancer tissues tested, and this was further confirmed in 56 breast cancer tissues by real-time RT-PCR. The function of lncRNA-BCHE in breast cancer cells was tested by knockdown and over-expression experiments in vitro. We also analyzed the public cohorts of breast cancer patients on the Kaplan Meier plotter platform. Clinical analysis revealed that the expression of lncRNA-BCHE was significantly correlated with advanced clinical stage and lymph node metastasis. Our data indicate that lncRNA-BCHE regulates the growth, migration and invasion of breast cancer cells. In addition, we found that these functions are mediated, at least in part, by the regulation of integrin subunit beta 1 (ITGB1) levels. The expression of ITGB1 serves as a negative prognostic factor and metastasis risk predictor in breast cancer, irrespective of subtype and therapeutic regimen. In summary, our results suggest that lncRNA-BCHE is an oncogenic lncRNA enhancing the growth and metastatic potential of breast cancer cells, and a potential predictor of breast cancer metastatic progression.