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    scaRNA1 Expression Levels Affect Alternative Splicing of mRNA

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    Our previous research identified 12 small Cajal body-specific RNAs (scaRNAs) with reduced expression in the right ventricle in infant patients with tetralogy of Fallot. Likewise, we showed that there were significant changes in mRNA processing in the RV in these patients. ScaRNAs play a crucial role in the biochemical maturation of spliceosomal RNAs (pseudouridylation and 2′-O-methylation). We showed that variations in scaRNA1 levels resulted in changes in alternative splicing in human cells. To investigate further the role that scaRNAs play in mRNA processing, we examine here the impact of knocking down scaRNA1 in quail myoblast cells (Coturnix japonica, a well-established animal model for studying embryonic development). Following the knockdown of scaRNA1, transcriptome analysis revealed that the genes Tjp1, Map3k7, and Sppl2a were alternatively spliced. Growing evidence indicates that alternative splicing of mRNA plays an important role in regulating cell differentiation and tissue development. Our data presented here provide additional support for research to clarify the specific roles that individual scaRNAs play in regulating spliceosome function and mRNA splicing

    Anatomical Variations of the Deep Plantar Arterial Arch: Surgical Implications for Partial Foot Amputations and Soft Tissue Reconstruction

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    Background: The forefoot receives its primary blood supply through the deep plantar arterial arch, typically formed by an anastomosis between the deep branch of the lateral plantar artery and the deep plantar artery. Accurate identification and localization of the deep plantar arch are critical during flap procedures and transmetatarsal amputations to minimize the risk of vascular compromise. Purpose: To assess the anatomical variability, dominance patterns, and location of the deep plantar arch to inform surgical planning and reduce intraoperative vascular complications. Study design: This was a descriptive anatomical study conducted through cadaveric dissection. Methods: Eighty-nine feet from 45 formalin-embalmed cadavers were dissected, with associated arteries traced from their origins and external diameters measured to determine arterial dominance. Distances from key anatomic landmarks were recorded to identify the arch\u27s position within the foot. Results: The deep plantar arch was present in all specimens. Lateral plantar artery dominance and deep plantar artery dominance were each observed in 42.70%, while co-dominance occurred in 12.36%, and medial plantar artery dominance in 2.25%. On average, the arch was located 58.48% of the distance from the calcaneal tuberosity to the distal phalanx. Medial deviation of the arch was found to be influenced by biological sex and the type of vascular dominance. Conclusion: The deep plantar arch demonstrates variability in both its dominance patterns and anatomic position. These findings underscore the importance of preoperative vascular assessment to optimize surgical outcomes and reduce the risk of ischemic complications during forefoot procedures

    Anti-nociceptive Properties of Cardiopulmonary Baroreceptors in Patients With Chronic Back Pain

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    Introduction: Reduced pain perception following a persistent noxious stimulus during a study session (short-term habituation) is believed to be partially mediated by descending inhibitory mechanisms, although these mechanisms have not been fully elucidated. We examined the hypothesis that cardiopulmonary baroreceptor would significantly increase short-term habituation in chronic back pain (CBP) patients. Methods: A short-term habituation protocol was utilized that involved 1-sec pulses (×10) at 105% heat pain threshold on the anterior forearm at 0.5 Hz. Cardiopulmonary baroreceptor unloading was performed via lower body negative pressure (LBNP) that reduces central venous pressure to elicit a reflex increase in sympathetic nerve activity. Results: Short-term habituation was observed in young, healthy participants (n = 11), as indicated by a reduction in subjective pain ratings across the 10 repetitive heat pulses (-42% ± 29, P \u3c 0.01, n = 11). Short-term habituation was also observed in CBP patients (-32% ± 30, P \u3c 0.01, n = 12). Cardiopulmonary baroreceptor unloading via LBNP significantly reduced pain ratings across the 10 repetitive heat pulses in CBP patients compared with supine control (patient positioned in LBNP chamber but without a reduction in pressure) and upright sitting (chair), as indicated by a more negative area under the curve index (LBNP: -16.3 ± 4.1; Control: -14.4 ± 2.6; Upright sitting: -15.1 ± 4.1, P = 0.02). However, LBNP-mediated reductions in pain ratings were selective to CBP patients with more severe symptoms, i.e., neuropathic pain (LBNP: -14.7 ± 2.1; Control: -12.8 ± 1.4; Upright sitting: -12.1 ± 1.2, P = 0.04), whereas no effect of LBNP was observed in young, healthy participants (P = 0.83). In support, CBP patients with neuropathic pain exhibited significantly elevated mechanical pressure pain threshold during LBNP (P = 0.04). Conclusions: Together, these findings demonstrate an association between cardiopulmonary baroreceptor unloading and a reduction in pain perception during repetitive noxious stimuli in CBP patients, particularly among CBP patients with greater pain severity

    The Influence of the Head-hips Technique and Transfer Type on Shoulder Jerk

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    Objective: This study aimed to compare shoulder jerk magnitudes during level and floor transfers and evaluate the impact the head-hips technique on shoulder mechanics in full-time wheelchair users (WCUs). From an ergonomics perspective, elevated magnitudes in jerk are associated with overuse injuries. In other aspects of wheelchair biomechanics, such as propulsion kinematics, increased jerk at the shoulders during manual propulsion has been predictive of shoulder pain. Exploratorily, this study aimed to evaluate the influence of sex, weight, and physical activity on shoulder jerk. Design: Cross-sectional study. Setting: University-based laboratory in Champaign, USA. Participants: A convenient sample of full-time WCUs that could perform independent level and floor transfers were recruited for participation. Outcome Measures: Using Mann-Whitney U test, data was stratified based on transfer type and sex to determine if differences existed in shoulder jerk magnitudes across stratifications. Spearman\u27s correlation was conducted to assess relationships between shoulder jerk, body weight, physical activity, and trunk flexion (i.e. head-hips technique). Results: Peak and average shoulder jerk magnitudes were significantly greater during floor transfers compared to level transfers. Trunk flexion was negatively correlated to peak shoulder jerk and weight during level transfers. Physical activity was negatively correlated to average shoulder jerk during level transfers. Females experienced reduced shoulder jerk compared to males during level transfers. Conclusion: The use of head-hips technique and the higher levels of chronic physical activity may play a role in protecting the shoulders during transfer-related activities. Floor transfers may pose risks to shoulder health for WCUs that should be limited when possible. Clinicians should emphasize the importance of the head-hips technique and fitness for maintaining long-term shoulder health in WCUs

    Human Papillomavirus-related Oral Lesions in People With HIV: A 20-Year Multinational Cohort Analysis

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    Background/purposePeople with human immunodeficiency virus (PWH) are at increased risk of acquiring human papillomavirus (HPV) infection and subsequently developing HPV-related lesions. We aimed to determine the prevalence and strength of association between HPV-related oral lesions and HIV infection, using a large, real-world dataset. Materials and methodsThis retrospective cohort used 20 years of de-identified electronic health records from TriNetX (109 organizations, 24 countries). Adults ≥18 years with HIV (ICD-10 B20, LOINC antibodies 7917-8/7918-6, RNA 25835-0) were compared age and sex matched people without HIV. We quantified prevalence and associations for HPV-related benign lesions (papilloma, verruca, epithelial hyperplasia, condyloma) and malignant oropharyngeal cancer (tonsil/base of tongue; ICD-O). Analyses excluded pre-study lesions, assessed oropharyngeal squamous cell carcinoma (OPSCC) after HIV diagnosis, and examined smoking effects within PWH. ResultsIn 253,847 PWH, condyloma (8.73 %) was most common, followed by verruca vulgaris (4.39 %), oral papilloma (2.63 %), epithelial hyperplasia (0.10 %), and HPV-OPSCC (0.26 %). All lesions were significantly more frequent than in people without HIV controls. OPSCC prevalence was 0.19 % in non-smokers, higher with smoking (0.26 %; odds ratio = 1.77). Elevated odds for OPSCC persisted in non-smokers, underscoring increased HPV-OPSCC disease risk in PWH regardless of tobacco exposure. ConclusionPWH face increased susceptibility to HPV-related oral lesions, particularly benign variants and OPSCC, with smoking further amplifying this risk. Despite the relatively low prevalence of OPSCC, there remains a critical need for targeted HIV care—including routine oral examinations, HPV vaccination, smoking cessation support, and advanced diagnostic approaches—to enable precise, evidence-based prevention strategies

    Primary Care Physicians Prescribe Fewer Expensive Combination Medications than Dermatologists for Acne: A Retrospective Review

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    Background: Many dermatologic medications are available as expensive combination products, though their lower-cost, generic components are available. Underutilization of these cheaper replacements is common and influenced by several factors, including prescriber\u27s knowledge and disease severity. Objective: To characterize differences in prescribing patterns for high- vs lower-cost dermatologic agents for acne between dermatologists and primary care physicians (PCPs). Methods: Using an administrative insurance claims database, IQVIA PharMetrics Plus for Academics, we identified medication claims between January 01, 2017, and June 30, 2022. Inclusion criteria were claims for high-cost medications and lower-cost alternatives for patients diagnosed with acne. We excluded patients without continuous insurance enrollment for the previous year. Data collected included patient, prescriber, and prescription characteristics. Distribution of costs to payers and patients were compared using the Wilcoxon rank sum test. Results: We identified 7,843 patients with medication claims meeting inclusion and exclusion criteria. High- vs low-cost acne medications cost insurers a median 480.6(IQR:377.2535.2)vs480.6 (IQR: 377.2-535.2) vs 81.8 (IQR: 30.3-162.3), respectively, whereas patient burden was 60.0(IQR:40.0182.4)vs60.0 (IQR: 40.0-182.4) vs 15.0 (IQR: 10.0-35.4). Dermatologists prescribed the largest number of acne medications, 7,648 of 9,791 (78.1%), and a higher proportion of high-cost medications (7.8% vs 1.3% for PCPs, P \u3c 0.001). Median insurer cost was lower among dermatologists (86.9,IQR:33.6184.5)thanPCPs(86.9, IQR: 33.6-184.5) than PCPs (87.3, IQR: 87.3, P = 0.008), but means were higher (mean ± SD: 144.3±169.9vs144.3 ± 169.9 vs 119.5 ± 126.9, respectively). Median patient cost was higher for dermatologists (20.0,IQR:10.040.0)thanPCPs(20.0, IQR: 10.0-40.0) than PCPs (15.0, IQR: 10.0-25.0, P \u3c 0.001). The mean costs were similarly higher (mean ± SD: 49.8±105.6vs49.8 ± 105.6 vs 34.0 ± 60.9, respectively). Conclusions: Dermatologists prescribed a higher percentage of high-cost medications for acne. These differences resulted in a slightly higher distribution of costs to the patient but lower for the insurer, as median is a better indicator of the cost distribution. System processes to identify high-cost combination medications and provide low-cost alternatives may further reduce costs

    Oral Squamous Cell Carcinoma Risk and Magnitude of Association in Inherited Cancer Predisposition Syndromes: Evidence from a Large Real-World Cohort

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    Objective Inherited cancer predisposition syndromes (ICPS) are rare genetic disorders associated with elevated cancer risk. This study evaluates oral squamous cell carcinoma (OSCC) prevalence across selected ICPS (Fanconi anemia (FA), Plummer–Vinson syndrome (PVS), Cowden syndrome (CS), Li–Fraumeni syndrome (LFS), Dyskeratosis congenita (DC), and Xeroderma pigmentosum), quantifies risk magnitude, examines age at diagnosis, and assesses tobacco’s modifying effect on OSCC risk in these populations. Study Design We conducted a retrospective cohort study using the TriNetX Research Network, including patients with or without ICPS identified by ICD‑10 codes over a 20‑year period. OSCC cases were matched 1:1 by age and sex to controls. Analyses assessed prevalence, odds ratios, age at diagnosis, and the impact of tobacco use. Statistical significance was set at p \u3c 0.05. Result The prevalence of OSCC amongst ICPS patients ranged from 0.11% - 4.66%, with the highest in patients with FA. Among ICPS, only FA showed a markedly increased OSCC risk (OR = 40.63, p \u3c 0.01), while PVS and DC were inversely associated. ICPS patients developed OSCC at younger ages (p \u3c 0.0001). Smoking increased OSCC risk within ICPS (OR = 1.47), whereas non‑smokers with ICPS had reduced risk (OR = 0.78). Conclusion FA is strongly associated with OSCC; OSCC also occur in LFS and CS. ICPS patients present with OSCC at a younger age, supporting targeted screening for high‑risk ICPS populations

    Readability Analysis of AAOS and ASSH Shoulder and Elbow Patient Education Online Content: A 9-Year Follow-up Study

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    Given the progressive spread of medical misinformation, access to understandable educational content from trusted sources has become increasingly more crucial for patients. Online patient education materials, particularly from specialty organizations, have been criticized for being too complex for the average reader. It is advised that this information be at or below the 6th-grade reading level. This study is a 9-year follow-up to an analysis conducted in 2013 which evaluated the overall readability of educational articles from the American Academy of Orthopaedic Surgeons (AAOS) and American Society for Surgery of the Hand (ASSH) websites related to shoulder and elbow conditions. In the current investigation, 74 shoulder and elbow articles were assessed using the same methodology, which included analyzing the number of years since their last update, word count, percentage of passive sentences, Flesch Reading Ease score, Flesch-Kincaid grade level, Simple Measure of Gobbledygook (SMOG) grade, and New Dale-Chall grade level. No articles from either site were at or below the recommended 6th-grade reading level. Those from the AAOS were longer than those from the ASSH (P \u3c .001). The articles had a mean Flesch Reading Ease score of 53.8 vs. 58 (P = .01), Flesch-Kincaid grade level of 9.6 vs. 9.4, SMOG grade of 8.9 vs. 8.6, and New Dale-Chall grade of 10.5 vs. 10.1 for the AAOS and ASSH sites, respectively. Although no significant differences in the readability measures were noted between the 2013 and current AAOS articles, the current ASSH content had a significantly higher Flesch Reading Ease score (P = .01) and significantly lower Flesch-Kincaid (P = .04), SMOG (P = .03), and New Dale-Chall (P = .03) grade levels, than their 2013 counterparts. Although improvements have been made in the shoulder and elbow articles from the ASSH, there remains a need to further improve the readability of AAOS and ASSH online materials to better ensure adequate patient education

    Current Evidence for the Use of Jugular Vein Compression Collars in Sport: A Systematic Review

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    Sport-related concussions are a common type of brain injury, and the best treatment is prevention. Recently, external jugular vein compression collars have been worn by National Football League players, but the current evidence is limited. To the best of the authors\u27 knowledge, this is the first comprehensive, up-to-date systematic review addressing the use of jugular vein compression collars for decreasing concussion incidence in high-impact sports and activities. Overall, when compared to control, the results indicated that jugular vein compression collars resulted in significantly reduced white matter alteration, improved short-term neurocognitive outcomes, increased internal jugular vein cross-sectional area, decreased internal carotid artery cross-sectional area, and moderating effects on peak pulse pressure. There was no significant difference in concussion incidence rate between groups. While promising, these findings warrant future research to assess jugular vein compression collar\u27s role in concussion prevention, brain injury, and long-term neurocognitive outcomes. The authors are hopeful for the role jugular vein compression collars will play in the future

    Generative Artificial Intelligence Responses to Common Patient-Centric Hand and Wrist Surgery Questions: A Quality and Usability Analysis

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    Background: Due to the rapid evolution of generative artificial intelligence (AI) and its implications on patient education, there is a pressing need to evaluate AI responses to patients\u27 medical questions. This study assessed the quality and usability of responses received from two prominent AI platforms to common patient-centric hand and wrist surgery questions. Methods: Twelve commonly encountered hand and wrist surgery patient questions were inputted twice into both Gemini and ChatGPT, generating 48 responses. Each response underwent a content analysis, followed by assessment for quality and usability with three scoring tools: DISCERN, Suitability Assessment of Materials (SAM) and the AI Response Metric (AIRM). Statistical analyses compared the features and scores of the outputs when stratified by platform, question type and response order. Results: Responses earned mean overall scores of 55.7 (\u27good\u27), 57.2% (\u27adequate\u27) and 4.4 for DISCERN, SAM and AIRM, respectively. No responses provided citations. Wrist question responses had significantly higher DISCERN (p \u3c 0.01) and AIRM (p = 0.02) scores compared to hand responses. Second responses had significantly higher AIRM (p \u3c 0.01), but similar DISCERN (p = 0.76) and SAM (p = 0.11), scores compared to the first responses. Gemini\u27s DISCERN (p = 0.04) and SAM (p \u3c 0.01) scores were significantly higher than ChatGPT\u27s corresponding metrics. Conclusions: Although responses are generally \u27good\u27 and \u27adequate\u27, there is variable quality with respect to platform used, type of question and response order. Given the diversity of publicly available AI platforms, it is important to understand the quality and usability of information patients may encounter during their search for answers to common hand and wrist surgery questions. Level of Evidence: Level IV (Therapeutic)

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