This exploratory retrospective cohort analysis aimed to explore how algorithmic models may be able to identify important risk factors that may otherwise not have been apparent. Their association with injury was then assessed with more conventional data models. Participants were players registered on the England and Wales Cricket Board women's international development pathway (n=17) from April 2018 to August 2019 aged between 14-23 years (mean 18.
View Article and Find Full Text PDFThe traditional structural view of allostery defines this key regulatory mechanism as the ability of one conformational event (allosteric site) to initiate another in a separate location (active site). In recent years computational simulations conducted to understand how this phenomenon occurs in nuclear receptors (NRs) has gained significant traction. These results have yield insights into allosteric changes and communication mechanisms that underpin ligand binding, coactivator binding site formation, post-translational modifications, and oncogenic mutations.
View Article and Find Full Text PDFAccounting for protein flexibility is an essential yet challenging component of structure-based virtual screening. Whereas an ideal approach would account for full protein and ligand flexibility during the virtual screening process, this is currently intractable using available computational resources. An alternative is ensemble docking, where calculations are performed on a set of individual rigid receptor conformations and the results combined.
View Article and Find Full Text PDFThe capacity of proteins to adapt their structure in response to various perturbations including covalent modifications, and interactions with ligands and other proteins plays a key role in biological processes. Here, we explore the ability of molecular dynamics (MD), replica exchange molecular dynamics (REMD), and a library of structures of crystal-ligand complexes, to sample the protein conformational landscape and especially the accessible ligand binding site geometry. The extent of conformational space sampled is measured by the diversity of the shapes of the ligand binding sites.
View Article and Find Full Text PDFThis article summarizes the developments that led to the current approach to immunotherapy. These developments were characterized in the early years by empirically derived successive approximations to arrive at effective injection regimens, in the middle years by a sorting through of the wide variations in practice with placebo-controlled clinical trials, and more recently by a closer association of clinical and laboratory measures to better define evidence-based practices. The pace of investigation along with the scientific quality continues to increase.
View Article and Find Full Text PDFNine recombinant chicken skeletal alpha-tropomyosin proteins were prepared, eight C-terminal deletion constructs and the full length protein (1-81, 1-92, 1-99, 1-105, 1-110, 1-119, 1-131, 1-260 and 1-284) and characterized by circular dichroism spectroscopy and analytical ultracentrifugation. We identified for the first time, a stability control region between residues 97 and 118. Fragments of tropomyosin lacking this region (1-81, 1-92, and 1-99) still fold into two-stranded alpha-helical coiled-coils but are significantly less stable (T(m) between 26-28.
View Article and Find Full Text PDFContinuing education is vital for otolaryngologists to maintain and build on their knowledge base and skill sets. This article discusses the history of continuing medical education (CME) and describes the significant changes in CME that are currently underway. The development of CME has generally lagged behind other improvements in medical education.
View Article and Find Full Text PDFBackground: The aim of this study was to compare three different techniques for transsphenoidal pituitary surgery: (1) sublabial transseptal approach with microscopic resection, (2) transnasal transseptal approach with endoscopic resection, and (3) endoscopic approach with endoscopic resection.
Methods: We performed a retrospective review of 50 pituitary surgeries performed by the same neurosurgeon. Demographic, radiographic, and clinical data were collected.
Otitis externa can take an acute or a chronic form, with the acute form affecting four in 1,000 persons annually and the chronic form affecting 3 to 5 percent of the population. Acute disease commonly results from bacterial (90 percent of cases) or fungal (10 percent of cases) overgrowth in an ear canal subjected to excess moisture or to local trauma. Chronic disease often is part of a more generalized dermatologic or allergic problem.
View Article and Find Full Text PDFSide-chain backbone interactions (or "effects") between nearest neighbours may severely restrict the conformations accessible to a polypeptide chain and thus represent the first step in protein folding. We have quantified nearest-neighbour effects (i to i+1) in peptides through reversed-phase liquid chromatography (RP-HPLC) of model synthetic peptides, where L- and D-amino acids were substituted at the N-terminal end of the peptide sequence, adjacent to a L-Leu residue. These nearest-neighbour effects (expressed as the difference in retention times of L- and D-peptide diastereomers at pHs 2 and 7) were frequently dramatic, depending on the type of side-chain adjacent to the L-Leu residue, albeit such effects were independent of mobile phase conditions.
View Article and Find Full Text PDFCurr Allergy Asthma Rep
November 2004
Patients with chronic rhinosinusitis (CRS) and chronic rhinosinusitis with nasal polyposis (CRSwNP) commonly present with nasal obstruction, nasal discharge, facial pressure/pain, and hyposmia of prolonged duration. Recent evidence suggests that, despite clinical similarities, CRS and CRSwNP are distinct entities with separate inflammatory pathways and cytokine profiles. Antibiotics and nasal steroids are the mainstay of treatment in CRS, whereas combination systemic and nasal steroids are the foundation of CRSwNP management.
View Article and Find Full Text PDFAnaphylaxis is an amplified, harmful immunologic reaction that occurs after re-exposure to an antigen to which an organism has become sensitive. True anaphylaxis is a systemic reaction caused by antigen-specific cross-linking of IgE molecules or complement proteins on the surface of tissue mast cells and peripheral blood basophils, resulting in the immediate release of potent mediators. Immediate systemic reactions that resemble anaphylaxis but are not caused by an IgE-mediated immune response are referred to as anaphylactoid reactions.
View Article and Find Full Text PDFObjective: The effectiveness of topical intranasal steroids (INS) sprays for the treatment of allergic and nonallergic rhinitis may be limited by lack of instruction in the optimal spray technique. To determine whether the technique used affects the efficacy and safety of the product, this review of evidence had the goal of identifying and establishing a preferred method of applying INS sprays.
Study Design: A MEDLINE search of pertinent literature on 7 INS and 1 intranasal antihistamine spray preparations conducted with the use of appropriate search terms, yielded an initial 121 articles, 29 of which were identified as appropriate for review and grading for quality of evidence.
Treatment and cure of salivary gland neoplasms requires surgical intervention in most cases. For parotid neoplasms, the most common surgical procedure performed is the superficial parotidectomy with facial nerve preservation. Postoperative radiation therapy is indicated in high-grade salivary gland malignancies and malignancies with increased risk of locoregional recurrence.
View Article and Find Full Text PDFObjective And Study Design: We performed a retrospective study of 28 patients to evaluate the management and outcome of regional metastasis from nonmelanoma cutaneous malignancies.
Results: There were 25 squamous cell, 1 basal cell, and 2 eccrine carcinomas. The most common primary locations were the temple, ear, and cheek.