IFNh and IRF9 influence the transcription of MHCII mediated by IFNγ to maintain immune balance in sea perch lateolabrax japonicus.

The major histocompatibility complex class II (MHCII) molecules are crucial elements of the adaptive immune system, essential for orchestrating immune responses against foreign pathogens. However, excessive expression of MHCII can disrupt normal physiological functions. Therefore, the host employs various mechanisms to regulate MHCII expression and maintain immune homeostasis. Despite this importance, limited studies have explored the negative regulation of MHCII transcription in bony fish. In this study, we found that interferon h (IFNh), a subtype of type I IFN in sea perch Lateolabrax japonicus, could inhibit the activation of IFNγ induced-MHCII expression by modulating the transcription of the class II major histocompatibility complex transactivator (CIITA). Transcriptome analysis revealed 57 up-regulated and 69 down-regulated genes in cells treated with both IFNγ and IFNh compared to those treated with IFNγ alone. To maintain cellular homeostasis, interferon regulatory factor 9 (IRF9) was up-regulated following IFNγ stimulation, thereby preventing MHCII overexpression. Mechanistically, IRF9 bound to the CIITA promoter and suppressed its expression activated by IRF1. Furthermore, IRF9 inhibited the promoter activity of both MHCII-α and MHCII-ß induced by CIITA. Our findings highlight the roles of IFNh and IRF9 as suppressors regulating MHCII expression at different hierarchical levels. This study provides insights into the intricate regulation of antigen presentation and the foundation for further exploration of the interaction mechanisms between aquatic virus and fish.

Impact of treatment crossovers on clinical outcomes in the rate and rhythm control strategies for atrial fibrillation: Insights from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial.

We investigated the rates and reasons for crossover to alternative treatment strategies and its impact on mortality in patients who were enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Over a mean follow-up period of 3.5 years, 842 patients underwent crossover to the alternative treatment arms in AFFIRM. The rate of crossover from rhythm to rate control (594/2,033, 29.2%) was more frequent than the rate of crossover from rate to rhythm control (248/2,027, 12.2%, P < 0.0001). The leading reasons for crossover from rhythm to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover from rate to rhythm control were failure to control atrial fibrillation symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). This difference in crossover pattern was statistically significant (P < 0.0001). There was a significantly decreased risk of all-cause mortality (adjusted HR: 0.61, 95% CI: 0.48-0.78, P < 0.0001) and cardiac mortality (adjusted hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.43-0.88, P = 0.008) in the subgroup of patients who crossed over from rhythm to rate control as compared to those who continued in rhythm control. There was a nonsignificant trend toward decreased all-cause (adjusted HR: 0.76, 95% CI: 0.53-1.10, P = 0.14) and cardiac mortality (adjusted HR: 0.70, 95% CI: 0.42-1.18, P = 0.18) in patients who crossed over from rate to rhythm control as compared to those who continued rate control.

An investigation of the validity of the Work Assessment Triage Tool clinical decision support tool for selecting optimal rehabilitation interventions for workers with musculoskeletal injuries.

OBJECTIVE: To evaluate the concurrent validity of a clinical decision support tool (Work Assessment Triage Tool (WATT)) developed to select rehabilitation treatments for injured workers with musculoskeletal conditions. DESIGN: Methodological study with cross-sectional and prospective components. SETTING: Data were obtained from the Workers' Compensation Board of Alberta rehabilitation facility in Edmonton, Canada. SUBJECTS: A total of 432 workers' compensation claimants evaluated between November 2011 and June 2012. MAIN MEASURES: Percentage agreement between the Work Assessment Triage Tool and clinician recommendations was used to determine concurrent validity. In claimants returning to work, frequencies of matching were calculated and compared between clinician and Work Assessment Triage Tool recommendations and the actual programs undertaken by claimants. The frequency of each intervention recommended by clinicians, Work Assessment Triage Tool, and case managers were also calculated and compared. RESULTS: Percentage agreement between clinician and Work Assessment Triage Tool recommendations was poor (19%) to moderate (46%) and Kappa = 0.37 (95% CI -0.02, 0.76). The Work Assessment Triage Tool did not improve upon clinician recommendations as only 14 out of 31 claimants returning to work had programs that contradicted clinician recommendations, but were consistent with Work Assessment Triage Tool recommendations. Clinicians and case managers were inclined to recommend functional restoration, physical therapy, or no rehabilitation while the Work Assessment Triage Tool recommended additional evidence-based interventions, such as workplace-based interventions. CONCLUSIONS: Our findings do not provide evidence of concurrent validity for the Work Assessment Triage Tool compared with clinician recommendations. Based on these results, we cannot recommend further implementation of the Work Assessment Triage Tool. However, the Work Assessment Triage Tool appeared more likely than clinicians to recommend interventions supported by evidence; thus warranting further research.

Combative Sports Injuries: An Edmonton Retrospective.

OBJECTIVE: Mixed martial arts (MMA) is an increasingly popular combative sport involving aggressive techniques that present substantial injury risk. We examined the incidence and types of injuries sustained in MMA fights and compared this with injuries sustained in boxing matches. DESIGN: Consecutive Case Series. SETTING: We used data from post-fight medical examinations on all bouts in Edmonton, Canada, between 2000 and 2013. PARTICIPANTS: The participants were 1181 MMA competitors and 550 boxers. MAIN OUTCOME MEASURES: The attending physician conducted a mandatory post-fight examination of all fighters and documented the nature of injuries sustained. RESULTS: Boxers were significantly more likely not to experience injury (49.8% vs 59.4%, P < 0.001), whereas MMA fighters were significantly more likely to experience 1 injury (typically contusion/bruising, P < 0.001). Boxers were more likely to experience loss of consciousness (7.1% vs 4.2%, P = 0.01) and serious eye injury (1.1% vs 0.3%, P = 0.02). CONCLUSIONS: The overall injury incidence in MMA competitors appears slightly higher than for boxers, but MMA fighters experience more minor contusion/bruising injuries. Boxers are more likely to experience serious injury such as concussion/head trauma involving loss of consciousness or eye injury such as retinal detachment.

Clinical Decision Support Tools for Selecting Interventions for Patients with Disabling Musculoskeletal Disorders: A Scoping Review.

Purpose We aimed to identify and inventory clinical decision support (CDS) tools for helping front-line staff select interventions for patients with musculoskeletal (MSK) disorders. Methods We used Arksey and O'Malley's scoping review framework which progresses through five stages: (1) identifying the research question; (2) identifying relevant studies; (3) selecting studies for analysis; (4) charting the data; and (5) collating, summarizing and reporting results. We considered computer-based, and other available tools, such as algorithms, care pathways, rules and models. Since this research crosses multiple disciplines, we searched health care, computing science and business databases. Results Our search resulted in 4605 manuscripts. Titles and abstracts were screened for relevance. The reliability of the screening process was high with an average percentage of agreement of 92.3 %. Of the located articles, 123 were considered relevant. Within this literature, there were 43 CDS tools located. These were classified into 3 main areas: computer-based tools/questionnaires (n = 8, 19 %), treatment algorithms/models (n = 14, 33 %), and clinical prediction rules/classification systems (n = 21, 49 %). Each of these areas and the associated evidence are described. The state of evidentiary support for CDS tools is still preliminary and lacks external validation, head-to-head comparisons, or evidence of generalizability across different populations and settings. Conclusions CDS tools, especially those employing rapidly advancing computer technologies, are under development and of potential interest to health care providers, case management organizations and funders of care. Based on the results of this scoping review, we conclude that these tools, models and systems should be subjected to further validation before they can be recommended for large-scale implementation for managing patients with MSK disorders.

Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial.

PURPOSE: Optimization of the clinical management of screen-detected lung nodules is needed to avoid unnecessary diagnostic interventions. Herein we demonstrate the potential value of a novel radiomics-based approach for the classification of screen-detected indeterminate nodules. MATERIAL AND METHODS: Independent quantitative variables assessing various radiologic nodule features such as sphericity, flatness, elongation, spiculation, lobulation and curvature were developed from the NLST dataset using 726 indeterminate nodules (all ≥ 7 mm, benign, n = 318 and malignant, n = 408). Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) method for variable selection and regularization in order to enhance the prediction accuracy and interpretability of the multivariate model. The bootstrapping method was then applied for the internal validation and the optimism-corrected AUC was reported for the final model. RESULTS: Eight of the originally considered 57 quantitative radiologic features were selected by LASSO multivariate modeling. These 8 features include variables capturing Location: vertical location (Offset carina centroid z), Size: volume estimate (Minimum enclosing brick), Shape: flatness, Density: texture analysis (Score Indicative of Lesion/Lung Aggression/Abnormality (SILA) texture), and surface characteristics: surface complexity (Maximum shape index and Average shape index), and estimates of surface curvature (Average positive mean curvature and Minimum mean curvature), all with P<0.01. The optimism-corrected AUC for these 8 features is 0.939. CONCLUSIONS: Our novel radiomic LDCT-based approach for indeterminate screen-detected nodule characterization appears extremely promising however independent external validation is needed.

Correction: Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial.

[This corrects the article DOI: 10.1371/journal.pone.0196910.].

A Pilot Study Evaluating the Effectiveness of Platelet-Rich Plasma Therapy for Treating Degenerative Tendinopathies: A Randomized Control Trial with Synchronous Observational Cohort.

OBJECTIVE: This pilot study aimed to inform future research evaluating the effectiveness of Platelet Rich Plasma (PRP) injection for tendinopathy. DESIGN: Randomized control trial (RCT) and synchronous observational cohort studies. For the RCT, consecutive consenting patients treated at an academic sports medicine clinic were randomly assigned to either a PRP or placebo control group. SETTING: The Glen Sather Sport Medicine Clinic, Edmonton, Canada. PATIENTS: The RCT included 9 participants with rotator cuff tendinopathy. The cohort study included 178 participants with a variety of tendinopathies. INTERVENTIONS: Patients receiving PRP were injected with 4 ml of platelets into the supraspinatus and/or infraspinatus, while patients in the placebo group were injected with 4 ml of saline. All participants undertook a 3-month standardized, home-based, daily exercise program. MAIN OUTCOME MEASURES: Participants in the RCT were re-evaluated 3, and 6 months post-injection. Change scores before and after injection on pain, disability and MRI-documented pathology outcomes were compared. In the cohort study, pain and disability were measured at 1, 2 and 3 months post-injection. RESULTS: For the RCT, 7 participants received PRP and 2 received placebo injections. Patients receiving PRP reported clinically important improvements in pain (>1.5/10 on VAS), disability (>15 point DASH change), and tendon pathology while those receiving placebo injections did not. In the observational cohort, statistically and clinically significant improvements in pain and disability were observed. CONCLUSION: This pilot study provides information for planning future studies of PRP effectiveness. Preliminary results indicate intratendinous, ultrasound-guided PRP injection may lead to improvements in pain, function, and MRI-documented tendon pathology. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN68341698.