Human milk improves the oral bioavailability of the poorly water-soluble drug clofazimine.

Clofazimine is an emerging drug for the treatment of cryptosporidiosis in infants. As a poorly water-soluble drug, the formulation of clofazimine in age-appropriate vehicles is challenging and often results in the use of off-label formulations. Milk-based vehicles such as human milk and bovine milk have been investigated as age-appropriate formulations and shown to increase the solubilisation of poorly water-soluble drugs via enhanced solubility in lipid digestion products in vitro.

An Integrative Migraine Polygenic Risk Score Is Associated with Age at Onset But Not Chronification.

: Genome-wide association studies (GWASs) demonstrate a complex genetic landscape for migraine risk. Migraine polygenic risk scores (PRSs) developed from GWAS data may have utility for predicting disease course. We analyzed the strength of association between an integrative migraine PRS and age at onset and chronification.

Causal Interpretations of Correlational Evidence Regarding Violence.

Inferring causation from correlation can lead to erroneous explanations of violent behavior and the development and implementation of ineffective or even harmful interventions and policies. This article explores the inferences that violence researchers draw from evidence related to violent offending. We invited authors of articles published in violence journals to complete an online survey in which they were asked to identify a factor that may be a cause of violence, cite a study that demonstrates the factor is associated with violence, and provide their inferences from that study.

Infant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients.

Cannabinoids can save paediatric patients from harmful psychological conditions caused by epilepsy. However, the limited aqueous solubility of the drug presents a limitation to oral absorption and bioavailability. Previous studies have shown the enhancement of oral bioavailability for poorly water-soluble drugs using milk or milk-based products like infant formula as a novel lipid-based formulation, due to digestion of the lipids to enhance drug solubility that is particularly well suited to infants and in low economy settings.

Impact of bariatric surgery on cytochrome P 450 enzyme activity.

Bariatric surgeries are becoming more prevalent as obesity rates continue to rise. Being that it is an effective weight-loss procedure, it can induce significant anatomical, physiological, and metabolic alterations, which affect the pharmacokinetics of various medications. Cytochrome (CYP) P450 is a group of enzymes that are primarily responsible for metabolizing most medications.

Exploring the Underlying Constructs of Rape-Related Cognition Scales and Their Relationships With Sexual Aggression.

Rape-related cognitions (typically defined as encompassing any number of cognitive constructs) are thought to play a role in sexual aggression. However, rape-related cognition scales often assess these cognitive constructs as one. The purpose of this study is to explore the factor structure of these measures using a sample of 191 community men.

Characteristics associated with response to subcutaneously administered anti-CGRP monoclonal antibody medications in a real-world community cohort of persons living with migraine: A retrospective clinical and genetic study.

Objective: To evaluate response to anti-calcitonin gene-related peptide (CGRP) migraine preventives in a real-world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response.

Background: Erenumab-aooeb, fremanezumab-vrfm, and galcanezumab-gnlm target CGRP or its receptor; however, many patients are non-responsive.

Methods: In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti-CGRP migraine preventive between May 2018 and May 2021.

Effects of bariatric surgery on drug pharmacokinetics-Preclinical studies.

With the rising worldwide obesity rates, bariatric surgeries are increasing. Although the surgery offers an effective treatment option for weight loss, the procedure causes dramatic physiological and metabolic changes. Animal models in rodents provide a valuable tool for studying the systemic effects of the surgery.

Advanced Technologies and Automation in mES Cell Workflow.

Gene targeting in mouse ES cells replaces or modifies genes of interest; conditional alleles, reporter knock-ins, and amino acid changes are common examples of how gene targeting is used. To streamline and increase the efficiency in our ES cell pipeline and decrease the timeline for mouse models produced via ES cells, automation is introduced in the pipeline. Below, we describe a novel and effective approach utilizing ddPCR, dPCR, automated DNA purification, MultiMACS, and adenovirus recombinase combined screening workflow that reduces the time between therapeutic target identification and experimental validation.

ASIS-Seq: Transgene Insertion Site Mapping by Nanopore Adaptive Sampling.

Generation of transgenic mice by direct microinjection of foreign DNA into fertilized ova has become a routine technique in biomedical research. It remains an essential tool for studying gene expression, developmental biology, genetic disease models, and their therapies. However, the random integration of foreign DNA into the host genome that is inherent to this technology can lead to confounding effects associated with insertional mutagenesis and transgene silencing.

Controlling drug release by introducing lipase inhibitor within a lipid formulation.

Drug overdose connected to marketed pharmaceutical products, particularly opioids, occurs at an alarming rate. Novel strategies through innovative formulation approaches that reduce the likelihood of overdose while allowing safe therapeutic outcomes are urgently required. The current study provides a proof-of-concept for a new formulation approach by co-formulating drug with a lipase inhibitor within a solid lipid formulation in order to prevent or reduce the harmful effects of taking multiple doses of an oral solid dose form.

Carpenter Bees () Harbor a Distinctive Gut Microbiome Related to That of Honey Bees and Bumble Bees.

Eusocial corbiculate bees, including bumble bees and honey bees, maintain a socially transmitted core gut microbiome that contributes to digestion and pathogen defense. In contrast, solitary bees, which have fewer opportunities for direct interhost transmission, typically have less consistent microbiomes dominated by bacteria associated with pollen and food reserves. Carpenter bees (genus ) are long-lived bees that are not eusocial but that often live in shared nesting sites.

Towards mesoporous silica as a pharmaceutical treatment for obesity - impact on lipid digestion and absorption.

Mesoporous silica particles (MSPs) are emerging as an interesting option to reduce calorific uptake as a treatment for obesity and other metabolic conditions. However, their further development under the pharmaceutical regulatory framework is hindered by poor understanding of the mechanisms by which they exert their effects. In the current study the interaction of MSPs with the lipid digestion process is investigated, specifically interactions with lipase enzymes and lipid digestion products as a key contributing factor to lipid absorption and calorific intake.

Accelerated embryonic stem cell screening with a highly efficient genotyping pipeline.

Introduction: Gene targeting in mouse ES cells replaces or modifies genes of interest; conditional alleles, reporter knock-ins, and amino acid changes are common examples of how gene targeting is used. For example, enhanced green fluorescent protein or Cre recombinase is placed under the control of endogenous genes to define promoter expression patterns.

Methods And Results: The most important step in the process is to demonstrate that a gene targeting vector is correctly integrated in the genome at the desired chromosomal location.

Formation of Self-Assembled Mesophases During Lipid Digestion.

Lipids play an important role in regulating bodily functions and providing a source of energy. Lipids enter the body primarily in the form of triglycerides in our diet. The gastrointestinal digestion of certain types of lipids has been shown to promote the self-assembly of lipid digestion products into highly ordered colloidal structures.

Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort.

Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members.

Prolonged Plasma Exposure of the Kv1.3-Inhibitory Peptide HsTX1[R14A] by Subcutaneous Administration of a Poly(Lactic-co-Glycolic Acid) (PLGA) Microsphere Formulation.

This study evaluated the impact of poly(lactic-co-glycolic acid) (PLGA) microsphere formulations on in vitro release and in vivo plasma exposure of HsTX1[R14A], a potent inhibitor of the voltage-gated potassium channel Kv1.3, with potential to treat autoimmune conditions. Microspheres containing HsTX1[R14A] were prepared using different PLGA materials, including Resomer® RG502H, RG503H and PURASORB® PDLG 5004 (Purac).

Integration of innate immune signalling by caspase-8 cleavage of N4BP1.

Mutations in the death receptor FAS or its ligand FASL cause autoimmune lymphoproliferative syndrome, whereas mutations in caspase-8 or its adaptor FADD-which mediate cell death downstream of FAS and FASL-cause severe immunodeficiency in addition to autoimmune lymphoproliferative syndrome. Mouse models have corroborated a role for FADD-caspase-8 in promoting inflammatory responses, but the mechanisms that underlie immunodeficiency remain undefined. Here we identify NEDD4-binding protein 1 (N4BP1) as a suppressor of cytokine production that is cleaved and inactivated by caspase-8.

Sustained absorption of delamanid from lipid-based formulations as a path to reduced frequency of administration.

Delamanid is a poorly water-soluble drug currently being used for the treatment of tuberculosis. The high frequency of dosing leads to poor adherence for patients who live in lower economic and nomadic populations. Non-digestible self-assembling lipids as a formulation approach for poorly water-soluble drugs have previously been shown to extend the window of absorption through gastric retention.

Longitudinal Monitoring of Parkinson's Disease in Different Ethnic Cohorts: The DodoNA and LONG-PD Study.

Different factors influence severity, progression, and outcomes in Parkinson's disease (PD). Lack of standardized clinical assessment limits comparison of outcomes and availability of well-characterized cohorts for collaborative studies. Structured clinical documentation support (SCDS) was developed within the DNA Predictions to Improve Neurological Health (DodoNA) project to standardize clinical assessment and identify molecular predictors of disease progression.

Factors Affecting Cognition and Depression in Adult Patients with Epilepsy.

Background And Purpose: Epilepsy patients are more likely to experience depressive symptoms and cognitive impairment compared to individuals in the general population. As the reasons for this are not definitively known, we sought to determine what factors correlate most strongly with cognition and a screening test for depression in epilepsy patients.

Methods: Our study population included 379 adult patients diagnosed with epilepsy or seizure in our neurology clinic.

Correlating Digestion-Driven Self-Assembly in Milk and Infant Formulas with Changes in Lipid Composition.

Lipids in mammalian milks such as bovine milk and human breast milk have been shown to self-assemble into various liquid crystalline materials during digestion. In this study, the direct correlation between the composition of the lipids from three types of mammalian milk, three brands of infant formulas (IFs), and soy milk and the liquid crystalline structures that form during their digestion was investigated to link the material properties to the composition. The self-assembly behavior was assessed using digestion coupled with small-angle X-ray scattering (SAXS).

Challenges to Introducing Integrated Diabetes Care to an Inner-Regional Area in South Western Sydney, Australia.

Introduction: Diabetes care often requires collaboration between general practitioners, allied health professionals, nurses, and/or medical specialists. This study aimed to describe the establishment of an integrated diabetes prevention and care approach in an area with limited access to primary and secondary care, and the challenges faced in its initial development.

Description: A qualitative research approach to identify challenges was taken.