Background: Patient-reported outcome measures (PROMs) have become crucial in assessing cataract surgery, especially with increasing patient expectations. The RayPro database offers a platform for tracking PROMs after surgery. The purpose of this study is to investigate determinants of patient satisfaction following cataract surgery by analysing PROMs.
View Article and Find Full Text PDFDisease-modifying treatments for Alzheimer's disease are emerging. Our research examined how personal risk for AD may influence intentions to ask for medications to delay symptoms of AD, and how the availability of such medications impacts interest in AD-related genetic testing. Invitations to a web-based survey were posted on social media sites.
View Article and Find Full Text PDFAdv Health Sci Educ Theory Pract
October 2022
Purpose: The National Academy of Medicine has called for "identifying opportunities to improve the diagnostic process". We studied the association between problem representation and diagnostic accuracy during an objective structured clinical exam (OSCE).
Materials And Methods: We conducted a non-randomized controlled trial during a ten-case OSCE.
Background: Free Open-Access Medical education (FOAM) use among residents continues to rise. However, it often lacks quality assurance processes and residents receive little guidance on quality assessment. The Academic Life in Emergency Medicine Approved Instructional Resources tool (AAT) was created for FOAM appraisal by and for expert educators and has demonstrated validity in this context.
View Article and Find Full Text PDFObesity is a global epidemic that causes morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the central nervous system and is a prime target for anti-obesity drugs. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human MC4R-G signaling complex bound to the agonist setmelanotide, a cyclic peptide recently approved for the treatment of obesity.
View Article and Find Full Text PDFEarly Huntington's disease (HD) include over-activation of dopamine D receptors (DR), producing an imbalance in dopaminergic neurotransmission and cell death. To reduce DR over-activation, we present a strategy based on targeting complexes of DR and histamine H receptors (HR). Using an HD mouse striatal cell model and HD mouse organotypic brain slices we found that DR-induced cell death signaling and neuronal degeneration, are mitigated by an HR antagonist.
View Article and Find Full Text PDFThe C57BL/6J and C57BL/6N mice have well-documented phenotypic and genotypic differences, including the infamous nicotinamide nucleotide transhydrogenase () null mutation in the C57BL/6J substrain, which has been linked to cardiovascular traits in mice and cardiomyopathy in humans. To assess whether loss alone causes a cardiovascular phenotype, we investigated the C57BL/6N, C57BL/6J mice and a C57BL/6J-BAC transgenic rescuing NNT expression, at 3, 12, and 18 mo. We identified a modest dilated cardiomyopathy in the C57BL/6N mice, absent in the two B6J substrains.
View Article and Find Full Text PDFProg Mol Biol Transl Sci
December 2020
This chapter will focus on the therapeutic potential of oligomeric GPCR structures. We will discuss the history of these complexes and their connection with treatment. We will highlight several examples from the literature of complexes of therapeutic or theranostic opportunity.
View Article and Find Full Text PDFAntibodies have found applications in several fields, including, medicine, diagnostics, and nanotechnology, yet methods to modulate antibody-antigen binding using an external agent remain limited. Here, we have developed photoactive antibody fragments by genetic site-specific replacement of single tyrosine residues with photocaged tyrosine, in an antibody fragment, 7D12. A simple and robust assay is adopted to evaluate the light-mediated binding of 7D12 mutants to its target, epidermal growth factor receptor (EGFR), on the surface of cancer cells.
View Article and Find Full Text PDFMembrane proteins can associate into larger complexes. Examples include receptor tyrosine complexes, ion channels, transporters, and G protein-coupled receptors (GPCRs). For the latter, there is abundant evidence indicating that GPCRs assemble into complexes, through both homo- and heterodimerization.
View Article and Find Full Text PDFAdeno-associated viruses (AAV) are attractive templates for engineering of synthetic gene delivery vectors. A particularly powerful technology for breeding of novel vectors with improved properties is DNA family shuffling, i.e.
View Article and Find Full Text PDFThe 5-HTR agonist lorcaserin, clinically approved for the treatment of obesity, causes important side effects mainly related to subtype selectivity. In the search for 5-HTR allosteric modulators as safer antiobesity drugs, a chemical library from Vivia Biotech was screened using ExviTech platform. Structural modifications of identified hit VA240 in synthesized analogues 6-41 afforded compound 11 (N-[(1-benzyl-1H-indol-3-yl)methyl]pyridin-3-amine, VA012), which exhibited dose-dependent enhancement of serotonin efficacy, no significant off-target activities, and low binding competition with serotonin or other orthosteric ligands.
View Article and Find Full Text PDFBackground: Bariatric surgery has become an increasingly popular method for weight loss and mitigation of co-morbidities in the obese population. Like any field, there is a desire to standardize and accelerate the postoperative period while maintaining safe outcomes.
Methods: All laparoscopic sleeve gastrectomies (LSG) and gastric bypasses (LGB) were performed over a 5-year period were logged along with several aspects of postoperative care.
Serotonin 5-HT receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer's disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4.
View Article and Find Full Text PDFThe dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A receptor (AR) and cannabinoid CB receptor (CBR), are of pivotal importance in the control of neuronal excitability.
View Article and Find Full Text PDFInjury of the CA1 subregion induced by a single injection of kainic acid (1 × KA) in juvenile animals (P20) is attenuated in animals with two prior sustained neonatal seizures on P6 and P9. To identify gene candidates involved in the spatially protective effects produced by early-life conditioning seizures we profiled and compared the transcriptomes of CA1 subregions from control, 1 × KA- and 3 × KA-treated animals. More genes were regulated following 3 × KA (9.
View Article and Find Full Text PDFMechanically separated seal meat (MSSM) at 10% (SM-10) and 20% (SM-20) or seal protein hydrolysate (SPH) at 1% (SPH-1) and 2% (SPH-2) prepared from MSSM were used to replace mechanically separated chicken meat (MSCM) in salami formulations. Cured products containing 10 or 20% MSSM had a deeper red colour than those of the controls as noted by Hunter L and a values. Samples containing 20% MSSM had a softer texture as determined by sensory and Kramer shear-compression test studies, which was supported by scanning electron micrographs.
View Article and Find Full Text PDFA renin-secreting tumour has been observed in a 32-year-old female with severe hypertension known for 17 years. The excision of the tumour lead to the complete normalisation of the blood pressure. Histological examination showed that the tumour was benign, contained secretion granules at different stages of maturation, and derived from the juxta-glomerular apparatus.
View Article and Find Full Text PDF3,3',5-Tri-iodo-L-thyronine (L-T3) binding sites from rat erythrocyte membranes were solubilized in an active form by using the zwitterionic detergent CHAPS or the anionic detergent lauroylsarcosine. The binding protein was successively purified by Sephadex G-200 and affinity chromatography. The purified material retained its binding activity and exhibited high affinity and specificity compared with those displayed in the original membrane.
View Article and Find Full Text PDF3,5,3'-Triiodo-L-thyronine (L-T3)-binding sites from rat and human red cells were characterized as to their distribution between the two surfaces of the membrane. Analysis of L-T3 binding to sealed right-side-out and inside-out vesicles from erythrocyte membrane revealed that high affinity L-T3-binding sites are located on the external side in rat erythrocytes and on the internal side in human red cells. These results were further confirmed by preincubation of intact red cells with p-chloromercuribenzoate, a slowly permeant reagent that interacts reversibly with SH groups of proteins.
View Article and Find Full Text PDFThe number of binding sites for L-triiodothyronine in rat erythrocyte membranes was increased 2-fold by incubation at 37 degrees C for 60 min. An increase of approximately 3-fold was found when the incubation was carried out at 50 degrees C. The proteinase inhibitor phenylmethylsulfonyl fluoride abolished the effect.
View Article and Find Full Text PDFA case is reported, in which a patient 54 years old, was admitted after a SAH. The CT Scan (D1) demonstrated blood in the peri-peduncular cisterns. A first angiogram through femoral route was performed at D1.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 1985
A thyroid binding peripheral membrane protein(s) has been characterized in human red cell. Two classes of affinity sites for triiodothyronine have been demonstrated. The high affinity, low capacity site showed values for dissociation constant of 2 X 10(-10)M.
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