Mckeehaastrup0673
To determine (1) frequency of resident research projects being in the same orthopaedic subspecialty that they ultimately choose for fellowship and practice; (2) percentage of research projects that were published.
Resident Thesis Day programs were independently assessed by two reviewers from 2010 to 2020. BTK inhibitor Reviewers classified projects based on orthopaedic subspecialty Spine, Joints, Trauma, Hand, Foot and Ankle, Sports, Pediatrics, Oncology, and Shoulder Elbow. Presenting residents' fellowship subspecialty, current practice specialty, and geographic state of current practice were collected using internet searches. Correlation of residents who completed a thesis day project in the same subspecialty as their fellowship and current practice was calculated.
A total of 81 resident physicians, 11 (13.6%) female, were included. In the entire cohort, 50.6% did a thesis day project in a different field than their current or projected subspecialty. Of those who completed, or are currently completing fellowship, 3riculums to focus more on research principles than specific orthopedic content.
The mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediator on childhood overweight, alone and sequentially to each metabolite.
Within four European birth-cohorts (N = 375 mother-child dyads), information on seven prenatal exposures (maternal education, pre-pregnancy BMI, weight gain and tobacco smoke during pregnancy, age at delivery, parity, and child gestational age), selected as obesogenic according to a-priori knowledge, was collected. Cord blood levels of 31 metabolites, associated with rapid postnatal growth and/or childhood overweight in a previous study, were measured via liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry. Rapid growth at 12 months and childhood overweight (including obesity) between fourildhood overweight. We did not find evidence supporting a mediating role of the studied metabolites alone between the studied prenatal exposures and the propensity to childhood overweight.
Our findings provide evidence of the involvement of in utero metabolism in the propensity to rapid postnatal growth and of rapid postnatal growth in the propensity to childhood overweight. We did not find evidence supporting a mediating role of the studied metabolites alone between the studied prenatal exposures and the propensity to childhood overweight.
To identify factors that patients consider when choosing between future in-person, video, or telephone visits.
Telemedicine has been rapidly integrated into ambulatory neurology in response to the COVID-19 pandemic.
Ambulatory neurology patients at a single center were contacted via telephone to complete (1) a survey quantifying likelihood of scheduling a future telemedicine visit, and (2) a semi-structured qualitative interview following their visit in March 2021. Data were processed using the principles of thematic analysis.
Of 2493 visits, 39% assented to post-visit feedback; 74% were in-person visits and 13% video and telephone. Patients with in-person visits were less likely than those with video and telephone visits to "definitely" consider a future telemedicine visit (36 vs. 59 and 62%, respectively; p < 0.001). Patients considered five key factors when scheduling future visits "Pros of Visit Type," "Barriers to Telemedicine," "Situational Context," "Inherent Beliefs," and "Extrinsic Variablcircumstances. Future care delivery models should incorporate the patient perspective to implement hybrid models where telemedicine is an adjunct to in-person visits in ambulatory neurology.
Sturge-Weber syndrome (SWS) is a neurocutaneous disorder caused by a somatic mutation in the GNAQ gene, leading to capillary venous malformations with neurological, ocular, and cutaneous abnormalities. Descriptions of adult and elderly patients with SWS are scarce compared to those of neonates or children.
We reviewed clinical, neuro-radiological and electroencephalographical findings of adult patients diagnosed with SWS, treated in our tertiary center for rare epilepsies.
Ten adult patients were identified with a median age of 48years at inclusion. All patients had seizures, with features of temporal lobe involvement for five patients. One patient presented typical drug-resistant mesial temporal seizures with ipsilateral hippocampal sclerosis and leptomeningeal enhancement, and was treated surgically. Other patients presented typical neurological and brain imaging features found in SWS. One patient without visible leptomeningeal angioma or brain calcifications presented neurological symptoms (tonic-clonic generalized seizures) for the first time at the age of 56. Two of the oldest patients in our cohort with supratentorial leptomeningeal angioma displayed contralateral cerebellar atrophy, consistent with crossed cerebellar diaschisis. Over 70years of follow-up data were available for one patient whose epilepsy started at the age of 6months, offering a vast overview of the course of SWS, in particular the onset of dementia and contralateral micro-bleeds in relation to the leptomeningeal angioma.
The long follow-up of our cohort allows for a description of the course of SWS and a characterization of uncommon neurological features in adult and elderly patients.
The long follow-up of our cohort allows for a description of the course of SWS and a characterization of uncommon neurological features in adult and elderly patients.Sphingosine 1-phosphate (S1P), which acts via G protein-coupled S1P receptors (S1PRs), is a bioactive lipid essential for vascular integrity and lymphocyte trafficking. The S1P-S1PR signalling axis is a key component of the inflammatory response in autoimmune rheumatic diseases. Several drugs that target S1PRs have been approved for the treatment of multiple sclerosis and inflammatory bowel disease and are under clinical testing for patients with systemic lupus erythematosus (SLE). Preclinical studies support the hypothesis that targeting the S1P-S1PR axis would be beneficial to patients with SLE, rheumatoid arthritis (RA) and systemic sclerosis (SSc) by reducing pathological inflammation. Whereas most preclinical research and development efforts are focused on reducing lymphocyte trafficking, protective effects of circulating S1P on endothelial S1PRs, which maintain the vascular barrier and enable blood circulation while dampening leukocyte extravasation, have been largely overlooked. In this Review, we take a holistic view of S1P-S1PR signalling in lymphocyte and vascular pathobiology. We focus on the potential of S1PR modulators for the treatment of SLE, RA and SSc and summarize the rationale, pathobiology and evidence from preclinical models and clinical studies. Improved understanding of S1P pathobiology in autoimmune rheumatic diseases and S1PR therapeutic modulation is anticipated to lead to efficacious and safer management of these diseases.Our incomplete understanding of the causes and pathways involved in the onset and progression of multiple sclerosis (MS) limits our ability to effectively treat this complex neurological disease. Recent studies explore the role of immune cells at different stages of MS and how they interact with cells of the central nervous system (CNS). The findings presented here begin to question the exclusivity of an antigen-specific cause and highlight how seemingly distinct immune cell types can share common functions that drive disease. Innovative techniques further expose new disease-associated immune cell populations and reinforce how environmental context is critical to their phenotype and subsequent role in disease. Importantly, the differentiation of immune cells into a pathogenic state is potentially reversible through therapeutic manipulation. As such, understanding the mechanisms that provide plasticity to causal cell types is likely key to uncoupling these disease processes and may identify novel therapeutic targets that replace the need for cell ablation.Cyclopiazonic acid (CPA) is a secondary metabolite produced by Aspergillus and Penicillium, which is present in contaminated crops and food, causing severe toxicity to humans and animals. Heterophil extracellular traps (HETs) are a novel host innate immune mechanism of chicken heterophils against pathogen infection. However, whether CPA can cause immunotoxicity of heterophils on HETs release remains unclear. Here, we attempt to detect the effects of CPA on HETs release, and further investigate the molecular mechanisms underlying these processes. We exposed heterophils to 2.5, 5, 10 μM CPA for 90 min. The results showed that CPA induced the release of HETs in heterophils, consisting of DNA-modified citrullinated histone 3 and elastase. The quantitative analysis of HETs content was positively correlated with CPA concentration. CPA also promoted reactive oxygen species production and phosphorylation of ERK1/2 and p38. In addition, CPA-triggered HETs formation was reduced by NADPH oxidase, ERK1/2, and p38 signaling pathway and glycolysis inhibitors, indicating that CPA-induced HETs were related to the production of ROS dependent on NADPH oxidase, ERK1/2, and p38 signaling pathways, as well as glycolysis. Our study describes the underlying mechanism of CPA-induced HETs release, which may provide a further understanding of the immunotoxicology of CPA poisoning.Red blood cells (RBCs) are cleared from the circulation when they become damaged or display aging signals targeted by macrophages. This process occurs mainly in the spleen, where blood flows through submicrometric constrictions called inter-endothelial slits (IES), subjecting RBCs to large-amplitude deformations. In this work, RBCs are circulated through microfluidic devices containing microchannels that replicate the IES. The cyclic mechanical stresses experienced by the cells affect their biophysical properties and molecular composition, accelerating cell aging. Specifically, RBCs quickly transition to a more spherical, less deformable phenotype that hinders microchannel passage, causing hemolysis. This transition is associated with the release of membrane vesicles, which self-extinguishes as the spacing between membrane-cytoskeleton linkers becomes tighter. Proteomics analysis of the mechanically aged RBCs reveals significant losses of essential proteins involved in antioxidant protection, gas transport, and cell metabolism. Finally, it is shown that these changes make mechanically aged RBCs more susceptible to macrophage phagocytosis. These results provide a comprehensive model explaining how physical stress induces RBC clearance in the spleen. The data also suggest new biomarkers of early "hemodamage" and inflammation preceding hemolysis in RBCs subjected to mechanical stress.Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis is a newly discovered method of programmed cell death and opens a new direction for GBM treatment. However, poor blood-brain barrier (BBB) penetration, reduced tumor targeting ability, and potential compensatory mechanisms hinder the effectiveness of ferroptosis agents during GBM treatment. Here, a novel composite therapeutic platform combining the magnetic targeting features and drug delivery properties of magnetic nanoparticles with the BBB penetration abilities and siRNA encapsulation properties of engineered exosomes for GBM therapy is presented. This platform can be enriched in the brain under local magnetic localization and angiopep-2 peptide-modified engineered exosomes can trigger transcytosis, allowing the particles to cross the BBB and target GBM cells by recognizing the LRP-1 receptor. Synergistic ferroptosis therapy of GBM is achieved by the combined triple actions of the disintegration of dihydroorotate dehydrogenase and the glutathione peroxidase 4 ferroptosis defense axis with Fe3 O4 nanoparticle-mediated Fe2+ release.
