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Introduction: It has been reported that even with the same body mass index (BMI), there are subjects with metabolically healthy or unhealthy phenotype. The main determinants of the unhealthy phenotype are the type and distribution of fat, ectopic fat accumulation, genetics, and lifestyle factors. Uncoupling proteins (UCPs) disengage mitochondrial respiration from ATP synthesis and result in heat production, which in turn is related to energy expenditure and, thus, to fat mass accumulation.
View Article and Find Full Text PDFDevelopment and external validation of the SMASHERS risk prediction model for aneurysmal subarachnoid haemorrhage in the general population: a population-based prospective cohort study.
BMJ Open
January 2025
Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, Netherlands
Objectives: Aneurysmal subarachnoid haemorrhage (ASAH) is a severe stroke type, preventable by screening for intracranial aneurysms followed by treatment in high-risk individuals. We aimed to develop and validate a risk prediction model for ASAH in the general population to identify high-risk individuals.
Design: We used the population-based prospective cohort studies of the United Kingdom (UK) Biobank for model development and the Trøndelag Health (HUNT) Study for model validation.
Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.
Target Oncol
January 2025
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Background: Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).
Objective: We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).
Patients And Methods: Eligible patients had pathologically confirmed advanced ccRCC.
Familial hypercholesterolemia - Targeted whole gene sequencing as a diagnostic approach.
Atheroscler Plus
March 2025
Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Background And Aims: Familial hypercholesterolemia (FH) and other disorders with similar features are common genetic disorders that remain underdiagnosed and undertreated, due in part to the cost of screening. The aim of this study was to design and implement a whole gene targeted NGS panel for the molecular diagnosis of FH and statin intolerance with an emphasis on high quality variant calling, including copy number analysis.
Methods: A whole gene panel for hybridisation-based short read NGS was designed for the dominant FH-genes low density lipoprotein receptor (), apolipoprotein B (APOB), proproteinconvertas subtilisin/kexin type 9 (PCSK9), apolipoprotein E (APOE) and the recessive FH-genes low density lipoprotein receptor adaptor protein 1 (), ATP binding cassette subfamily member 5/8 (ABCG5/8) and lipase A, lysosomal acid type (), as well as solute carrier organic anion transporter family member 1B1 (), not an FH gene but linked to statin intolerance.
Direct and transgenerational effects of simvastatin on the metabolism of the amphipod Gammarus locusta.
Aquat Toxicol
December 2024
Department of Chemistry and CICECO, Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address:
In this study, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was applied for the first time, to our knowledge, to assess the metabolic impact of direct and transgenerational exposure (F0 and F3 generations, respectively) of amphipods Gammarus locusta to simvastatin (SIM), a pharmaceutical widely prescribed for the treatment of hypercholesterolemia. Results revealed the important gender-dependent nature of each of these effects. Directly exposed males showed enhanced glucose catabolism and tricarboxylic acid (TCA) cycle activity, in tandem with adaptations in osmotic regulation and glyoxylate metabolism.
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