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Macrocyclization as a Strategy for Kinetic Solubility Improvement: A Comparative Analysis of Matched Molecular Pairs.
J Med Chem
January 2025
Department Chemistry and Biochemistry, Clemens-Schöpf-Institute, Technical University Darmstadt, Darmstadt 64287, Germany.
In recent years, rationally designed macrocycles have emerged as promising therapeutic modalities for challenging drug targets. Macrocycles can improve affinity, selectivity, and pharmacokinetic (PK) parameters, possibly via providing semirigid, preorganized scaffolds. Nevertheless, how macrocyclization affects PK-relevant properties is still poorly understood.
View Article and Find Full Text PDFMoral conflict and moral distress in veterinarians: a mixed-methods approach.
Aust Vet J
January 2025
Centre for Wellbeing Science, Faculty of Education, The University of Melbourne, Carlton, Victoria, Australia.
Veterinary professionals are often confronted with moral conflicts from which moral distress can develop. Moral distress can lead to a cascade of deleterious processes and outcomes including emotional anguish, distress, reduced patient care, and attrition from both the workplace and workforce. The current study established a pilot measure for moral distress in Australian veterinary clinicians, as well as reporting additional sources of moral and ethical conflicts in veterinary practice.
View Article and Find Full Text PDFDyslipidemia: recommendations for diagnosis and treatment at the first level of medical contact.
Gac Med Mex
January 2025
Clínica de Hipertensión y Riesgo Cardiovascular, ISSSTESon, Hermosillo, Sonora. México.
Cardiovascular disease is the main cause of mortality in Mexico as well as the rest of the world, with dyslipidemia being one of the main risk factors. Despite the importance of its epidemiological impact, there is still -among primary care physicians- a lack of knowledge ranging from the basic concepts for diagnosis to the most recent recommendations for treatment. This document consisting of 10 questions is done by experts in this field.
View Article and Find Full Text PDFThe eukaryotic genome is broadly transcribed by RNA polymerase II (RNAPII) to produce protein-coding messenger RNAs (mRNAs) and a repertoire of non-coding RNAs (ncRNAs). Whereas RNAPII is very processive during mRNA transcription, it terminates rapidly during synthesis of many ncRNAs, particularly those that arise opportunistically from accessible chromatin at gene promoters or enhancers. The divergent fates of mRNA versus ncRNA species raise many questions about how RNAPII and associated machineries discriminate functional from spurious transcription.
View Article and Find Full Text PDFThe effect of prosthetic alignment on lower limb kinetics in people with a transtibial bone-anchored prosthesis: An experimental within-subject study.
Gait Posture
January 2025
Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam and Amsterdam Movement Sciences, Amsterdam, the Netherlands; Department of Research and Development, Military Rehabilitation Centre Aardenburg, Doorn, the Netherlands.
Background: The alignment of a bone-anchored prosthesis has consequences for the external moments around the residual joints and implant, and these external moments can lead to serious negative long-term effects. A clear understanding of the relationship between transtibial prosthetic alignment and external joint and implant moment for bone-anchored prosthetic users is still lacking.
Research Question: What is the effect of systematic frontal plane prosthetic alignment changes on lower limb external joint moments in people with a transtibial bone-anchored prosthesis?
Methods: Participants underwent gait analysis on an instrumented dual belt treadmill.
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