Effect of Genetic Variants on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Involvement of , and .

Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the and genes to minimize ADRs and improve treatment efficacy.

Optimizing spherulation cues in the fungal pathogen .

spp. are part of a group of thermally dimorphic fungal pathogens, which grow as filamentous cells (hyphae) in the soil and transform to a different morphology upon inhalation into the host. The host form, the spherule, is unique and highly undercharacterized due to both technical and biocontainment challenges.

Clinical Features and Outcomes of Pediatric -Related Dilated Cardiomyopathy.

Background: Although genetic variants in are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric -related DCM.

Methods And Results: We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.

Characterization of macrocyclic peptide drug interactions with bile salts and biorelevant colloids via single amino acid mutations and H nuclear magnetic resonance (NMR) spectroscopy.

There is growing interest in the oral delivery of poorly permeable peptide drugs; however, the effect of biorelevant colloids found in the aqueous gastrointestinal environment on peptide drug solution behavior has been largely understudied. In this work, we detail the molecular level interactions between octreotide, a water-soluble macrocyclic peptide drug, and biorelevant colloids, i.e.

A Mixed Methods Evaluation of Pharmacists' Readiness to Provide Long-Acting Injectable HIV Pre-exposure Prophylaxis in California.

Background: Pre-exposure prophylaxis (PrEP) uptake remains low among people who could benefit, some of whom may prefer alternatives to oral PrEP, such as long-acting injectable pre-exposure prophylaxis (LAI-PrEP). We evaluated the potential for LAI-PrEP provision in pharmacies through a mixed methods study of pharmacists in California, where Senate Bill 159 enables pharmacists to independently provide oral PrEP.

Methods: In 2022-2023, we conducted an online cross-sectional survey of California pharmacists and pharmacy students (n = 919) and in-depth interviews with pharmacists (n = 30), both of which included modules assessing attitudes about PrEP provision.

Community-based natural resource management in Roatan: Strengths and challenges.

This study explored the transformative journey of community-based natural resource management (CBNRM) in the Bay Islands National Marine Park, Honduras, revealing the interplay of cooperation, funding, and communication in fostering successful conservation initiatives. Using a mixed-method approach, we investigated the historical and legislative process and enabling conditions that led to the transition to CBNRM, based on Gruber's 12 key principles. In regards to the present CBNRM system, we looked at its strengths, its challenges, and whether its functioning is seen as satisfying by local resource-users.

High Resolution Ion Mobility Enables the Structural Characterization of Atropisomers of GDC-6036, a KRAS G12C Covalent Inhibitor.

GDC-6036 is a covalent KRAS G12C inhibitor that demonstrates high potency and selectivity. Structurally, GDC-6036 consists of several motifs that make the analytical characterization of this molecule challenging, including a highly basic pyrrolidine motif bonded to a quinazoline ring via an ether bond and an atropisomeric carbon-carbon bond between functionalized pyridine and quinazoline groups. Structurally, the desired atropisomer was synthesized via an atroposelective Negishi coupling with very high yield.

Rare Genetic Variants in Young Adults Requiring Pacemaker Implantation.

Background: Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled.

Objectives: This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups.

A Survey of Current Approaches to Inguinal Hernia Repair by Pediatric General Surgeons in the United States.

Introduction: Inguinal hernia repair (IHR) is a common pediatric operation performed via open or laparoscopic approaches. The objective of this survey study was to assess current approaches to IHR in a national sample of pediatric general surgeons.

Methods: A REDCap survey was distributed to all pediatric general surgeons at 21 US institutions in 2023.

Allostasis, health, and development in Latin America.

The lifespan is influenced by adverse childhood experiences that create predispositions to poor health outcomes. Here we propose an allostatic framework of childhood experiences and their impact on health across the lifespan, focusing on Latin American and Caribbean countries. This region is marked by significant social and health inequalities nested in environmental and social stressors, such as exposure to pollution, violence, and nutritional deficiencies, which critically influence current and later-life health outcomes.

Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

Background: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown.

Objectives: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development.

Methods: The authors evaluated 779 G+ patients (age 35.

Willingness of Pharmacists to Prescribe Medication Abortion in California.

Importance: Nearly half of US states have restricted abortion access. Policy makers are exploring pathways to increase access to abortion and reproductive health care more broadly. Since 2016, California pharmacists could prescribe hormonal birth control, providing an opportunity to learn about the implementation of pharmacist-provided reproductive health care.

Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC.

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018.

Food Administration and Not Genetic Variants Causes Pharmacokinetic Variability of Tadalafil and Finasteride.

Tadalafil and finasteride are used in combination for the management of benign prostatic hyperplasia (BPH). Genetic variations in genes involved in the metabolism and transport of tadalafil or finasteride (i.e.

The effect of tube quality on externally calibrated quantitative nuclear magnetic resonance analysis: How bad can it be?

Externally calibrated quantitative nuclear magnetic resonance (NMR) approaches offer practical means to simultaneously evaluate chemical identity and content without the addition of calibrants to the test sample. Despite continuous advances in external calibration over the last few decades, adoption of these approaches has been slower than expected. Variations in NMR tube geometry are a commonly overlooked factor that can have a substantial effect on externally calibrated quantitation methods.

Long-term Ecological Research: Chasing fashions or being prepared for fashion changes?

Long-term-ecological-research (LTER) faces many challenges, including the difficulty of obtaining long-term funding, changes in research questions and sampling designs, keeping researchers collecting standardized data for many years, impediments to interactions with local people, and the difficulty of integrating the needs of local decision makers with "big science". These issues result in a lack of universally accepted guidelines as to how research should be done and integrated among LTER sites. Here we discuss how the RAPELD (standardized field infrastructure system), can help deal with these issues as a complementary technique in LTER studies, allowing comparisons across landscapes and ecosystems and reducing sampling costs.

Treatment Modality Impact on Patient-Reported Quality of Life in Human Papilloma Virus-Associated Oropharyngeal Carcinoma.

Objective: To prospectively compare the impact of treatment modality on patient-reported quality of life (QOL) in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC).

Study Design: Prospective cohort study.

Setting: Academic medical center.

Late gadolinium enhancement distribution patterns in non-ischaemic dilated cardiomyopathy: genotype-phenotype correlation.

Aims: Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM); there is little information about its frequency and distribution pattern according to the underlying genetic substrate. We sought to describe LGE patterns according to genotypes and to analyse the risk of major ventricular arrhythmias (MVA) according to patterns.

Methods And Results: Cardiac magnetic resonance findings and LGE distribution according to genetics were performed in a cohort of 600 DCM patients followed at 20 Spanish centres.