Foot Model, Sectioned

For further information and availability, please visit the model\u27s catalogue record: https://jefferson.primo.exlibrisgroup.com/permalink/01TJU_INST/1ckporg/alma991000119769703866.https://jdc.jefferson.edu/scottlibrary_anatomy_models/1014/thumbnail.jp

Transcription Factor RUNX1 Regulates Coagulation Factor XIII-A (F13A1): Decreased Platelet-Megakaryocyte F13A1 Expression and Clot Contraction in RUNX1 Haplodeficiency

BACKGROUND: Germline RUNX1 haplodeficiency (RHD) is associated with thrombocy- topenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased F13A1, encoding for the A subunit of factor (F)XIII, a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes. OBJECTIVES: o understand RUNX1 regulation of F13A1 expression in platelets/mega- karyocytes and the mechanisms and consequences of decreased F13A1 in RHD. METHODS: We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown (KD) of RUNX1 or F13A1. RESULTS: Platelet F13A1 mRNA and protein were decreased in our index patient and in 2 siblings from an unrelated family with RHD. Platelet-driven clot contraction was decreased in the patient and affected daughter. Promoter studies in HEL cells showed that RUNX1 regulates F13A1 transcription; RUNX1 overexpression increased, and small inhibitor RNA RUNX1 KD reduced F13A1 promoter activity and protein. Following RUNX1 or F13A1 KD, clot contraction by HEL cells was decreased, as were FXIII-A surface expression, myosin light chain phosphorylation, and PAC1 antibody binding upon activation. F13A1 expression and clot contraction were impaired in RUNX1 downregulation in human megakaryocytes. CONCLUSION: RUNX1 regulates platelet-megakaryocyte F13A1 expression, which is decreased in RHD, reflecting regulation of a coagulation protein by a hematopoietic transcription factor. Platelet and megakaryocyte clot contraction is decreased in RHD, related to multiple impaired mechanisms including F13A1 expression, myosin phos- phorylation, and αIIbβ3 activation

Sirt6 Deficiency Promotes Senescence and Age-Associated Intervertebral Disc Degeneration in Mice

Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (AcanCreERT2; Sirt6fl/fl). Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months, which became pronounced at 24 months. RNA-Seq analysis of NP and AF tissues, in vitro quantitative histone analysis, and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape. A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells. Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21, p19, γH2AX, IL-6, IL-1β, and TGF-β abundance. Taken together, our study highlights the contribution of SIRT6 in modulating DNA damage, autophagy, and cell senescence and its importance in maintaining disc health during aging, thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration

Management of Parkinson\u27s Disease Psychosis: First-Line Antipsychotic Selection and Rationale for Continuing, Combining, or Switching

INTRODUCTION: The past decade has seen a paradigm shift in the evaluation and management of Parkinson\u27s disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson\u27s disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. Despite advances in the understanding of PDP and the approval of pimavanserin in the US, clinical questions concerning patient selection, treatment timing, switch strategies, and combination therapy remain. AREAS COVERED: To develop a consensus on first-line and subsequent treatment strategies for PDP, a panel of experts reviewed the clinical presentation and course of PDP, then discussed clinical trial evidence and experience. EXPERT OPINION: PDP is a common but still undertreated sequela of PD progression. Pimavanserin is recommended as a first-line antipsychotic therapy based on its established safety and efficacy. While switching strategies are suggested, further study is needed to assess combination antipsychotic therapy

An Assessment of the Performance of Different Chatbots on Shoulder and Elbow Questions

Background/Objectives: The utility of artificial intelligence (AI) in medical education has recently garnered significant interest, with several studies exploring its applications across various educational domains; however, its role in orthopedic education, particularly in shoulder and elbow surgery, remains scarcely studied. This study aims to evaluate the performance of multiple AI models in answering shoulder- and elbow-related questions from the AAOS ResStudy question bank. Methods: A total of 50 shoulder- and elbow-related questions from the AAOS ResStudy question bank were selected for the study. Questions were categorized according to anatomical location, topic, concept, and difficulty. Each question, along with the possible multiple-choice answers, was provided to each chatbot. The performance of each chatbot was recorded and analyzed to identify significant differences between the chatbots\u27 performances across various categories. Results: The overall average performance of all chatbots was 60.4%. There were significant differences in the performances of different chatbots (p = 0.034): GPT-4o performed best, answering 74% of the questions correctly. AAOS members outperformed all chatbots, with an average accuracy of 79.4%. There were no significant differences in performance between shoulder and elbow questions (p = 0.931). Topic-wise, chatbots did worse on questions relating to Adhesive Capsulitis than those relating to Instability (p = 0.013), Nerve Injuries (p = 0.002), and Arthroplasty (p = 0.028). Concept-wise, the best performance was seen in Diagnosis (71.4%), but there were no significant differences in scores between different chatbots. Difficulty analysis revealed that chatbots performed significantly better on easy questions (68.5%) compared to moderate (45.4%; p = 0.04) and hard questions (40.0%; p = 0.012). Conclusions: AI chatbots show promise as supplementary tools in medical education and clinical decision-making, but their limitations necessitate cautious and complementary use alongside expert human judgment

Cardiac Screening Findings and Referral Patterns in Male African-American Basketball Players: Analysis of the HeartBytes Registry

Sudden cardiac death (SCD) is the leading medical cause of death in young athletes. Male African American basketball players (MABP) demonstrate particularly elevated risk for SCD. Despite increasing screening and preventative efforts, the incidence of SCD remains elevated in this population. This retrospective analysis of the HeartBytes National Youth Cardiac Registry (2015-2023) aimed to characterize cardiac screening findings, including symptoms, family history, physical exam, and electrocardiogram (ECG) abnormalities in MABP compared to other youth athletes undergoing cardiac screening. We secondarily examined referral patterns based on screening results between the two groups. Of 8,303 individuals screened, 200 MABP were identified. MABP were found to have higher rates of chest pain during exercise (10.0% vs. 4.8%, p\u3c 0.001), easily tiring with exercise (13.0% vs. 7.0%, p=0.003), and heart murmurs (8.9% vs. 4.4%, p=0.008) when compared to the rest of the population screened. ECG abnormalities, including T-wave inversions (4.0% vs. 0.8%, p\u3c 0.001), ST-segment depressions (0.5% vs. 0.05%, p=0.01), and nonspecific ST-T wave changes (2.0% vs. 0.4%, p\u3c 0.001), were more prevalent in MABP. However, positive screening rates leading to referral to a cardiologist were similar (3.5% vs. 3.2%, p=0.842) in MABP and the rest of the screened population. In conclusion, MABP exhibited higher rates of concerning cardiac screening findings compared to non-MABP, including symptoms, physical examination findings, and ECG abnormalities, highlighting the need for further investigation into optimizing screening strategies and determining appropriate follow-up in this high-risk group

Evaluating Bone Fracture Healing in a Rabbit Model Using Doppler Imaging Modes, Shear Wave Elastography, X-Ray, and Dual-Energy X-Ray Absorptiometry

OBJECTIVE: This study investigated methods of evaluating the bone fracture healing process using superb microvascular imaging (SMI; two modes color SMI [cSMI] and monochromeSMI [mSMI]), and shear wave elastography (SWE), relative to X-ray, dual-energy X-ray absorptiometry (DXA), and platelet endothelial cell adhesion molecule 1 (PECAM-1) also know as cluster of differentiation 31 (CD-31) staining in a rabbit model. METHODS: This IACUC-approved study involved eight rabbits that underwent a bilateral fibula osteotomy and were followed for 7 or 21 days (Groups 1 and 2 with 4 rabbits in each). Ultrasound examinations using cSMI, mSMI, and SWE were performed on Days 0, 4, 7, 14, and 21 post-surgery. At the final time point, rabbits had X-ray imaging followed by euthanasia and DXA scan. Finally, the fracture areas underwent decalcification, and specimens were stained with CD-31 for pathological analysis. Ultrasound and X-ray findings were compared using ANOVAs or paired t-tests with CD-31 stains and DXA was used as a reference. RESULTS: Comparing SMI ultrasound images between the last time points for Group 1 (Day 7) and Group 2 (Day 21) showed no statistical significance difference for cSMI (P = .14) and mSMI (P = .06), similarly when compared with CD-31 stains there was no statistical significance difference for cSMI in Group 2 (P = .13). The SWE ultrasound images from the last time points in Groups 1 and showed no statistical significance difference (P = .33), the same results were then compared with DXA and also showed no statistical significance difference (P = .14). When comparing results of the X-ray images from the last time points for Groups 1 and 2 a statistical significance difference was found (P = .01), and when X-ray images were compared with DXA there was a statistical significance difference (P \u3c  .001). CONCLUSION: Compared with CD-31 stains cSMI on Day 21 was not statistically significant (P = .13). Results comparing SWE with DXA were also not statistically significant (P = .14). These results indicate the potential of using certain ultrasound imaging techniques to monitor the bone fracture healing process

Increased Rates of Dysphagia, Longer Length of Stay, Nonroutine Discharge, and Higher Hospital Costs in Patients Over 65 Undergoing Single-Level Cervical Disc Arthroplasty: A Propensity Score-Matched Analysis

CONTEXT: Cervical disc arthroplasty (CDA) is a safe and effective treatment for cervical spine conditions, with increasing utilization. As the population over 65 grows, understanding the suitability of CDA in older patients is critical. AIMS: This study evaluates differences in postoperative complications, hospital course, and costs between patients aged 18 and 65 and those over 65 undergoing CDA. SETTINGS AND DESIGN: This was a retrospective cohort study using the National Inpatient Sample, a nationally representative database of U.S. hospital discharges. SUBJECTS AND METHODS: Patients undergoing single-level CDA from 2016 to 2020 were identified. The cohort was divided into two groups: 18-65 years and \u3e65 years. Propensity score matching (1:5) was applied based on sex, race, obesity, chronic lung disease, and the Elixhauser Comorbidity Index. Outcomes included postoperative complications, length of stay (LOS), hospital costs, and discharge disposition. Statistical significance was set at P \u3c 0.05. STATISTICAL ANALYSIS USED: Propensity score matching ensured group balance. Chi-square tests and Student\u27s t-tests assessed outcomes, with a Benjamini-Hochberg adjustment for multiple comparisons. RESULTS: After matching, 4550 cases from the 18 to 65 years of group and 910 from the \u3e65 group were analyzed. Dysphagia rates were higher in the older cohort (8.8% vs. 3.8%, P = 0.007). LOS was significantly longer for older patients (2.15 ± 0.20 days vs. 1.38 ± 0.04 days, P \u3c 0.001). Hospital costs were higher in the \u3e65 group ($25,900 ± 1000 vs.$22,500 ± 400, P = 0.005), and nonroutine discharge was more common (19.2% vs. 7.1%, P \u3c 0.001). CONCLUSIONS: Older patients undergoing CDA experience more complications, longer hospital stays, and higher costs, highlighting the need for tailored care strategies

Relationship Between Maternal Iron Indices in the Second Trimester with Cord Blood Iron Indices and Pregnancy Outcomes: A Prospective Cohort Study

Background/Objectives: Iron deficiency anemia in pregnancy poses risks to mothers and infants. This study aimed to correlate maternal iron indices in the second trimester with cord blood indices and pregnancy outcomes. Methods: This prospective cohort study was nested within the RAPIDIRON Trial (Reducing Anaemia in Pregnancy in India) at Jawaharlal Nehru Medical College, Karnataka, India. A total of 292 pregnant women with moderate anemia who received oral iron supplementation were enrolled from April 2021 to May 2023. Maternal iron indices were measured at multiple time points and correlated with cord blood indices and pregnancy outcomes. Results: Increased hemoglobin levels were observed in mothers of preterm and term neonates from 8.92 ± 0.81 vs. 9.02 ± 0.77 g/dL at 12–16 weeks to 11.14 ± 1.31 vs. 10.73 ± 1.24 g/dL at 26–30 weeks. A similar trend was observed in mothers across birth weight groups. Ferritin and TSAT levels significantly increased in all outcome groups (p \u3c 0.001), peaking at 20–24 weeks and then slightly declining at 26–30 weeks. Additionally, maternal sTfR levels significantly improved from the early (7.72 ± 1.33 vs. 7.51 ± 1.61) to late second trimester (5.87 ± 0.81 vs. 5.76 ± 1.11) in mothers of both anemic and non-anemic neonates (p \u3c 0.001). Maternal sTfR in other outcome groups also showed a similar pattern. A negligible correlation was found between maternal and cord blood iron indices. Conclusions: Maternal iron indices increased from the early to mid-second trimester, followed by a slight fall in the late second trimester. Notably, higher iron indices were observed in mothers of preterm and low-birth-weight neonates