Background: The societal value of cats, dogs and horses is high, and the companion and sport animal health care sector is growing. Clinical research concerning cats, dogs and horses is crucial for the development of evidence-based medical care that benefits animals and their owners, and has implications for human and environmental health from a One Health perspective. Basic information on companion animal and equine research enables more directed measures to improve conditions for research within the area.
View Article and Find Full Text PDFThe rapid advancements in biomedical sciences, including genomics, microbiome research, and bioinformatics, underscore the need for dental education to evolve to meet future challenges in public oral health and healthcare delivery. The integration of basic sciences into dental curricula is crucial to ensure that dental professionals are thoroughly prepared in these fundamental areas. Despite the widespread agreement on the necessity of including basic medical sciences in dental education, challenges such as curricular congestion, faculty economics, and infrastructural limits persist, complicating the integration of new scientific knowledge.
View Article and Find Full Text PDFThis work introduces a high-throughput setup for Raman analysis of various flowing fluids, both transparent and non-transparent. The setup employs a microfluidic cell, used with an external optical setup, to control the sample flow's position and dimensions 3-dimensional hydrodynamic focusing. This approach, in contrast to the prevalent use of fused silica capillaries, reduces the risk of sample photodegradation and boosts measurement efficiency, enhancing overall system throughput.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
A mechanistic investigation into the novel combination of the -halogen effect with enantioselective aminocatalysis unravels the mechanistic intricacies of [6 + 4] and [10 + 6] higher-order cycloadditions and the succeeding new Favorskii-like rearrangements. By introducing the OTf-group into the tropone framework, it can serve both as an activator for the cycloaddition and as a proficient leaving group within the corresponding cycloadduct, thus enabling unprecedented ring-contracting Favorskii-like rearrangements. Integrating the -OTf group creates an electron-deficient 6π-component leveraging the -halogen effect by enhancing the polarization and introducing new strategic interaction points.
View Article and Find Full Text PDFBackground: Shared decision making in healthcare is a fundamental right for patients. Healthcare professionals' perception of their own abilities to enable shared decision making is crucial for implementing shared decision making within service. IcanSDM (I can shared decision making) is a brief measure to investigate healthcare professionals' perception of shared decision making approaches to their practices.
View Article and Find Full Text PDFThe serotonin transporter (SERT), responsible for the reuptake of released serotonin, serves as a major target for antidepressants and psychostimulants. Nevertheless, refining the mechanistic models for SERT remains challenging. Here, we expand the molecular understanding of the binding of ions, substrates, and inhibitors to SERT by incorporating the fluorescent non-canonical amino acid Anap through genetic code expansion.
View Article and Find Full Text PDFThe diagnostic accuracy of handheld ultrasound (HHUS) devices operated by newly certified operators for pneumonia is unknown. This multicenter diagnostic accuracy study included patients prospectively suspected of pneumonia from February 2021 to February 2022 in four emergency departments. The index test was a 14-zone focused lung ultrasound (FLUS) examination, with consolidation with air bronchograms as diagnostic criteria for pneumonia.
View Article and Find Full Text PDFAims: PTC518 is an orally administered, centrally and peripherally distributed huntingtin (HTT) pre-mRNA splicing modifier being developed for the treatment of Huntington's disease (HD) for which there is a high unmet medical need as there are currently no approved disease-modifying treatments. This first-in-human study investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PTC518 in healthy volunteers.
Methods: This phase 1, single-centre, randomized study in 77 healthy male and female volunteers evaluated the safety and tolerability and PK of PTC518 following single ascending doses and multiple ascending doses, PD as assessed by HTT mRNA and HTT protein levels after single and multiple doses, and food effects.
Question: Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder.
Study Selection And Analysis: We conducted a systematic review with meta-analysis and trial sequential analysis.
Kainate receptors play an important role in the central nervous system by mediating postsynaptic excitatory neurotransmission and modulating the release of the inhibitory neurotransmitter GABA through a presynaptic mechanism. To date, only three structures of the ligand-binding domain (LBD) of the kainate receptor subunit GluK1 in complex with positive allosteric modulators have been determined by X-ray crystallography, all belonging to class II modulators. Here, we report a high-resolution structure of GluK1-LBD in complex with kainate and BPAM538, which belongs to the full-spanning class III.
View Article and Find Full Text PDFBackground And Objectives: There is a need for knowledge regarding the natural course of diabetic polyneuropathy (DPN), a complication in type 2 diabetes (T2D). The aim of this study was to examine the development of DPN over time.
Methods: Patients with newly diagnosed T2D, recruited from a national cohort, and controls without diabetes of similar age and sex, underwent sensory phenotyping in 2016-2018.
The substituted tetrahydrofuran core is a structural motif in many biologically active and natural compounds. However, the scarcity of enantioselective methods developed towards its synthesis makes this field challenging and attractive to explore. Herein, the first Brønsted-base catalyzed enantioselective (3+2) annulation of donor-acceptor cyclopropanes with aldehydes and ketones affording enantioenriched 2,3,5-substituted tetrahydrofurans is reported.
View Article and Find Full Text PDFInt J Cardiol Cardiovasc Risk Prev
September 2024
Background: The growing prevalence of obesity is expected to increase the burden of coronary artery disease. This study examined the prevalence of overweight and obesity in patients with a first-time diagnosis of obstructive coronary artery disease in a contemporary population. The association of body-mass-index (BMI) with age, traditional risk factors, and the presence of multivessel disease were explored.
View Article and Find Full Text PDFHealthcare research emphasises involvement of patients in the research process, recognizing that this can enhance the relevance, quality, and implementation of research. This article highlights the need for more systematic planning to successfully involve patients in research projects and provides guidance on key aspects that researchers should consider in the planning of involving patients in research. The article accentuates the importance of establishing clear frameworks and guidelines to promote transparency and facilitate implementation.
View Article and Find Full Text PDFMetastatic colorectal cancer (mCRC) presents significant challenges in clinical management due to its heterogeneity and variable response to treatment. In this study, we conducted comprehensive small RNA (sRNA) sequencing analyses to identify sRNA biomarkers associated with survival and treatment response in mCRC patients. We measured serum sRNAs before and after chemotherapy treatment in a discovery cohort of 189 mCRC patients.
View Article and Find Full Text PDFBackground And Objectives: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH.
Methods: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018.
The N-methyl-D-aspartate (NMDA) receptor is a glutamate-activated cation channel that is critical to many processes in the brain. Genome-wide association studies suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis. Here we report the engineering and preclinical development of a bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease.
View Article and Find Full Text PDFIntroduction: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia.
View Article and Find Full Text PDFVortioxetine (VTX) is a recently approved antidepressant that targets a variety of serotonin receptors. Here, we investigate the drug's molecular mechanism of operation at the serotonin 5-HT receptor (5-HTR), which features two properties: VTX acts differently on rodent and human 5-HTR, and VTX appears to suppress any subsequent response to agonists. Using a combination of cryo-EM, electrophysiology, voltage-clamp fluorometry and molecular dynamics, we show that VTX stabilizes a resting inhibited state of the mouse 5-HTR and an agonist-bound-like state of human 5-HTR, in line with the functional profile of the drug.
View Article and Find Full Text PDFBackground: Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is a central part of patient care. We investigated the natural history of cardiac involvement in patients with DM1 to provide an evidence-based foundation for adjustment of follow-up protocols.
Methods: Patients with genetically confirmed DM1 were identified.
A novel strategy that combines oxidative aminocatalysis and gold catalysis allows the preparation of chiral α-quaternary isochromanes, a motif that is prevalent in natural products and synthetic bioactive compounds. In the first step, α-branched aldehydes and propargylic alcohols are transformed into α-quaternary ethers with excellent optical purities (>90 % ee) via oxidative umpolung with DDQ and an amino acid-derived primary amine catalyst. Subsequent gold(I)-catalyzed intramolecular hydroarylation affords the isochromane products with retention of the quaternary stereocenter.
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