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Patellar dislocations commonly occur in young adults and often reduce spontaneously or with closed reduction in the emergency department. However, traumatic patellar dislocations in older adults pose unique challenges, often complicated by degenerative osteophytes that hinder standard closed reduction methods. When closed reduction proves ineffective, patients may necessitate arthroscopic or open surgical intervention. This case report details the experience of a 60-year-old man with a traumatic patellar dislocation resistant to standard closed reduction methods, attributed to impaction of the patella against a lateral femoral condyle osteophyte. We present a novel technique for addressing irreducible patellar dislocations through closed reduction, which has yet to be documented in existing literature., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Sentinel lymph node biopsy for melanoma determines treatment and prognostic factors and improves disease-specific survival. To risk-stratify patients for sentinel lymph node biopsy consideration, Memorial Sloan Kettering Cancer Center and Melanoma Institute Australia developed nomograms to predict sentinel lymph node positivity. We aimed to compare the accuracy of these 2 nomograms., Methods: A multi-institutional study of patients with melanoma receiving sentinel lymph node biopsy between September 2018 and December 2022 was performed. The accuracy of the 2 risk prediction tools in determining a positive sentinel lymph node biopsy was analyzed using receiver operating characteristic curves and area under the curve., Results: In total, 532 patients underwent sentinel lymph node biopsy for melanoma; 98 (18.4%) had positive sentinel lymph node. Increasing age was inversely related to sentinel lymph node positivity (P < .01); 35.7% of patients ≤30 years had positive sentinel lymph node compared with 9.7% of patients ≥75 years. When we analyzed the entire study population, accuracy of the 2 risk prediction tools was equal (area under the curve Memorial Sloan Kettering Cancer Center : 0.693; area under the curve MIA : 0.699). However, Memorial Sloan Kettering Cancer Center tool was a better predictor in patients aged ≥75 years (area under the curve Memorial Sloan Kettering Cancer Center : 0.801; area under the curve Melanoma Institute Australia : 0.712, P < .01) but Melanoma Institute Australia tool performed better in patients with a higher mitotic index (mitoses/mm 2 ≥2; area under the curve Memorial Sloan Kettering Cancer Center : 0.659; area under the curve Melanoma Institute Australia : 0.717, P = .027). Both models were poor predictors of sentinel lymph node positivity in young patients (age ≤30 years; area under the curve Memorial Sloan Kettering Cancer Center : 0.456; area under the curve Melanoma Institute Australia : 0.589, P = .283)., Conclusion: The current study suggests that the 2 risk stratification tools differ in their abilities to predict sentinel lymph node positivity in specific populations: Memorial Sloan Kettering Cancer Center tool is a better predictor for older patients, whereas Melanoma Institute Australia tool is more accurate in patients with a higher mitotic index. Both nomograms performed poorly in predicting sentinel lymph node positivity in young patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We selected statements in the Official Disability Guidelines that had the potential to reinforce misconceptions regarding symptoms from rotator cuff tendinopathy. These statements were revised and presented with the original statement to specialists., Methods: Twelve statements regarding rotator cuff tendinopathy were identified as deviating from principles based on ethics, values, and the evidence regarding both pathophysiology and human illness behavior. One hundred fifteen upper extremity surgeons reviewed both original and revised versions of the statements and indicated their preference., Results: We found that upper extremity surgeons preferred 3 revised statements, 4 Official Disability Guidelines statements, and 5 were rated as neutral between the 2 statements., Conclusions: Statements revised for evidence, ethics, and healthy mindset were not preferred by specialists, which may indicate limited awareness about how negative thoughts and distressing symptoms impact human illness., Competing Interests: Conflicts of interest and source of funding: One of the authors (D.R.) received royalties from Skeletal Dynamics for an internal joint stabilizer elbow in the amount of between US $10,000 and US $100,000 USD per year. One of the authors certifies that he (D.R.) is a Deputy Editor for Hand and Wrist, Journal of Orthopaedic Trauma, and Clinical Orthopaedics and Related Research, and has received or may receive payments or benefits in the amount of US $5000 per year. For the remaining authors, none were declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Readiness for practice (RFP) is essential as new nurses will practice in a nursing shortage climate, with high acuity patients and complex technology. Nurse educators are challenged to foster readiness for practice., Aim: The aim of this integrative review was to explore the impact of simulation and senior practicum on graduating senior nursing students' readiness for practice., Background: Readiness for practice has been a point of concern for healthcare for quite some time. This has led to a need for better understanding for what RFP means including their perceptions of various stakeholders. Further, it is important to address what teaching and learning strategies can be implemented to assist in ensuring the graduating senior nursing student is ready for practice on graduation and for their first professional practice. Readiness for practice is defined as the ability to safely and competently care for patients by synthesizing theory, skills, attitudes and values in applying clinical reasoning in practice settings., Method: An integrative review identified 48 published papers on simulation and senior practicum that met the inclusion criteria., Results: Themes identified from the senior practicum/preceptor literature included clinical reasoning, skills, barriers to the senior practicum and transition. Themes identified regarding simulation as a strategy included preparation, competence development, clinical reasoning and the number of human patient simulators used., Conclusion: Although the evidence is not conclusive, simulation and senior practicums have the promise of preparing graduating nursing students for their first professional practice. However, nurse educators must ensure simulations are well-organized with clear objectives and that preceptors are supported in teaching and assessing students., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα). However, in vitro, activation of PDGF-CC by tPA is very inefficient and the mechanism of PDGF-CC activation in the NVU is not known. Here, we show that the integrin Mac-1, expressed on brain microglia/macrophages (denoted microglia throughout), acts together with the endocytic receptor LRP1 in the NVU to promote tPA-mediated activation of PDGF-CC. Mac-1-deficient mice (Mac-1 -/- ) are protected from tPA-induced BBB permeability but not from permeability induced by intracerebroventricular injection of active PDGF-CC. Immunofluorescence analysis demonstrates that Mac-1, LRP1, and the PDGFRα all localize to the NVU of arterioles, and following middle cerebral artery occlusion (MCAO) Mac-1 -/- mice show significantly less PDGFRα phosphorylation, BBB permeability, and infarct volume compared to wild-type mice. Bone-marrow transplantation studies indicate that resident CD11b + cells, but not bone-marrow-derived leukocytes, mediate the early activation of PDGF-CC by tPA after MCAO. Finally, using a model of thrombotic stroke with late thrombolysis, we show that wild-type mice have an increased incidence of spontaneous ICH following thrombolysis with tPA 5 h after MCAO, whereas Mac-1 -/- mice are resistant to the development of ICH even with late tPA treatment. Together, these results indicate that Mac-1 and LRP1 act as co-factors for the activation of PDGF-CC by tPA in the NVU, and suggest a novel mechanism for tightly regulating PDGFRα signaling in the NVU and controlling BBB permeability.

Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC) within the brain can promote BBB permeability through PDGF receptor α (PDGFRα) signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRα, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRα.

Objective: A growing body of evidence suggests that increased blood-brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures., Methods: An experimental model of kainate-induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA (-/-) ), its inhibitor neuroserpin (Nsp (-/-) ), or both (Nsp:tPA (-/-) ), and in mice conditionally deficient in the platelet-derived growth factor receptor alpha (PDGFRα)., Results: Compared to wild-type (WT) mice, Nsp (-/-) mice have significantly reduced latency to seizure onset and generalization; whereas tPA (-/-) mice have the opposite phenotype, as do Nsp:tPA (-/-) mice. Furthermore, interventions that maintain BBB integrity delay seizure propagation, whereas osmotic disruption of the BBB in seizure-resistant tPA (-/-) mice dramatically reduces the time to seizure onset and accelerates seizure progression. The phenotypic differences in seizure progression between WT, tPA (-/-) , and Nsp (-/-) mice are also observed in electroencephalogram recordings in vivo, but absent in ex vivo electrophysiological recordings where regulation of the BBB is no longer necessary to maintain the extracellular environment. Finally, we demonstrate that these effects on seizure progression are mediated through signaling by PDGFRα on perivascular astrocytes., Interpretation: Together, these data identify a specific molecular pathway involving tPA-mediated PDGFRα signaling in perivascular astrocytes that regulates seizure progression through control of the BBB. Inhibition of PDGFRα signaling and maintenance of BBB integrity might therefore offer a novel clinical approach for managing seizures.

Objective: To determine disposition of cyproheptadine hydrochloride in cats after intravenous or oral administration of a single dose., Animals: 6 healthy cats., Procedure: A randomized crossover design was used, and each cat was studied after intravenous (2 mg) and oral (8 mg) administration of cyproheptadine. Blood samples were collected at fixed time intervals after drug administration, and serum cyproheptadine concentration was determined by means of polarized immunofluorescence., Results: Mean (+/- SD) residence time was significantly longer after oral (823 +/- 191 minutes) than after intravenous (339 +/- 217 minutes) administration, but no significant differences were detected between other pharmacokinetic parameters after oral and intravenous administration. Mean +/- SD oral bioavailability was 1.01 +/- 0.36. Mean elimination half-life after oral administration was 12.8 +/- 9.9 hours. Peak extrapolated cyproheptadine concentration was 669 +/- 206 ng/ml. Only 1 cat developed adverse effects (transient vocalization)., Conclusions: Cyproheptadine appeared to be well tolerated in cats and had high bioavailability after oral administration. The mean elimination half-life of 12 hours indicated that approximately 2.5 days must elapse to achieve steady-state concentrations of cyproheptadine after oral administration of multiple doses. A 12-hour dosing interval is acceptable, but an 8-hour interval may be indicated for some cats., Clinical Relevance: On the basis of pharmacokinetic parameters determined in this study, the oral form of cyproheptadine appears to be suitable for use in clinical trials to treat anorexia in cats. Its half-life is compatible with once or twice daily dosing.

The present study investigated the generalizability of Schmidt's (1975) schema theory to an open-skill (Poulton, 1957) situation. Subjects attempted to time a preferred-hand button press so that it was coincident with the lighting of the last of a series of run way lights whose apparent velocity was 4023 mm/sec. Prior to five trials of performance on the criterion task, subjects received 40 trials in which they either (a) watched (low response requirements) or (b) responded with the nonpreferred hand (high response requirements) to a stimulus moving at (a) a constant (2235, 3129, 4917, or 5812 mm/sec) velocity (low stimulus variability) or (b) different velocities (high stimulus variability) from trial to trial. Subjects receiving high stimulus variability and high response requirements during training had significantly lower absolute error on the criterion task than did those in the other conditions. The results were discussed in terms of the type of practice which facilitates development of a schema rule for coincident-timing situations.