Effect of Mild or Moderate Hepatic Impairment on the Pharmacokinetics of Avacopan, a Small-Molecule Complement C5a Receptor Antagonist, for the Treatment of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Avacopan is currently approved in several regions of the world as an oral treatment in combination with standard therapy, including glucocorticoids, for adult patients with severe active antineutrophil cytoplasmic autoantibody-associated vasculitis. In vitro and clinical studies have established that avacopan is primarily eliminated through cytochrome P450 3A4 metabolism. This Phase 1, open-label, single-dose study (ClinicalTrials.

Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic.

Objectives: Opioid use disorder (OUD) is a major public health concern in the USA, resulting in high rates of overdose and other negative outcomes. Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analysed the distribution of methadone for the treatment of OUD across the USA over the past decade and through the COVID-19 pandemic.

Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation.

Objective: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation."

Methods: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832).

Pronounced Regional Disparities in United States Methadone Distribution.

Background: Methadone is an evidence-based treatment for opioid use disorder (OUD) and pain management. Methadone for OUD may be difficult for some patients to access, particularly those in rural areas.

Objective: The purpose of this study was to characterize methadone distribution patterns between 2017 and 2019 across the United States.

Early lifecycle UV-exposure calibrates adult vitamin D metabolism: Evidence for a developmentally originated vitamin D homeostat that may alter related adult phenotypes.

Objectives: Within the Developmental Origins of Adult Disease (DOHaD) model, early life environmental exposures can confer a long-term legacy on human health. This mechanism may be adaptive or maladaptive depending on lifestyle circumstances. This article examines the role of first trimester UV-exposure on late-life vitamin D levels, and potentially related adaptive and maladaptive phenotypes (height and osteoporosis respectively).

Vitamin D and folate: A reciprocal environmental association based on seasonality and genetic disposition.

Objectives: The purpose of this study was (1) to elucidate any reciprocal seasonal relationship that might exist between red cell folate (RCF) and serum vitamin D Levels; (2) to explore whether folate-related gene variants that influence/alter DNA-thymidylate and methyl group biosynthesis modify any associations detected in objective 1; and (3) to consider whether these processes might influence reproductive success consistent with the "folate-vitamin D-UV hypothesis of skin pigmentation" evolutionary model.

Methods: A large (n = 649) Australian cross-sectional study population was examined. Polymerase chain reaction (PCR)/Restriction fragment length polymorphism (RFLP) analysis was used to genotype C677T-MTHFR, C1420T-SHMT, T401C-MTHFD and 2R > 3R-TS.

Photobiology of vitamins.

This review explores contemporary ideas about the relationship between light exposure and vitamin biology. Nutritional biochemistry has long recognized the relationship between vitamins A and D and light exposure, but in recent years other vitamins have also been implicated in photoresponsive biological mechanisms that influence health, well-being, and even evolutionary processes. Interactions between light and vitamins can modify genotype-phenotype relationships across the life cycle, providing a basis for interesting new explanations relevant to wide aspects of human biology.

VDR gene methylation as a molecular adaption to light exposure: Historic, recent and genetic influences.

Objectives: The vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors. We examined whether degree of VDR gene methylation acts as a molecular adaptation to light exposure. We explored this in the context of photoperiod at conception, recent UV irradiance at 305 nm, and gene-latitude effects.

Gelation of barramundi (Lates calcarifer) minced muscle as affected by pressure and thermal treatments at low salt concentration.

Background: Barramundi minced muscle with salt 10 g kg and 20 g kg added is gelled by different combinations of pressurisation (300, 400 and 500 MPa at 4 °C for 10 min), cooking (0.1 MPa, 90 °C for 30 min) and setting (0.1 MPa, 50 °C for 2 h) to improve mechanical properties of barramundi gels and reduce salt added to barramundi gels.

UV-associated decline in systemic folate: implications for human nutrigenetics, health, and evolutionary processes.

Objectives: The purpose of this study was to examine whether UV exposure alters folate status according to C677T-MTHFR genotype, and to consider the relevance of this to human health and the evolutionary model of skin pigmentation.

Methods: Total Ozone Mapping Spectrometer (TOMS) satellite data were used to examine surface UV-irradiance, as a marker of UV exposure, in a large (n = 649) Australian cross-sectional study population. PCR/RFLP analysis was used to genotype C677T-MTHFR.

Vitamin D Receptor Genotype Modulates the Correlation between Vitamin D and Circulating Levels of let-7a/b and Vitamin D Intake in an Elderly Cohort.

Background And Aims: Circulating microRNAs (miRNAs) are linked to disease and are potential biomarkers. Vitamin D may modulate miRNA profiles, and vitamin D status has been linked to risk of disease, including cardiovascular disease and cancers. We hypothesise that genotypic variance influences these relationships.

Vitamin D: Beyond Metabolism.

Interest in vitamin D and the VDR gene is increasing as putative roles in human health and evolutionary processes are explored. This review looks beyond the classic biochemistry that links vitamin D to calcium homeostasis; it explores how vitamin D interacts with light in a broader perspective than simple skin photosynthesis. It examines how the vitamin influences circadian rhythm, and how it may have helped drive the evolution of skin pigmentation.

Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes.

Background And Objectives: Vitamin D and folate are highly UV sensitive, and critical for maintaining health throughout the lifecycle. This study examines whether solar irradiance during the first trimester of pregnancy influences vitamin D receptor (VDR) and nuclear folate gene variant occurrence, and whether affected genes influence late-life biochemical/clinical phenotypes.

Methodology: 228 subjects were examined for periconceptional exposure to solar irradiance, variation in vitamin D/folate genes (polymerase chain reaction (PCR)), dietary intake (food frequency questionnaire (FFQ)) and important adult biochemical/clinical phenotypes.

Solar cycle predicts folate-sensitive neonatal genotypes at discrete phases of the first trimester of pregnancy: a novel folate-related human embryo loss hypothesis.

Folate, a key periconceptional nutrient, is ultraviolet light (UV-R) sensitive. We therefore hypothesise that a relationship exists between sunspot activity, a proxy for total solar irradiance (particularly UV-R) reaching Earth, and the occurrence of folate-sensitive, epigenomic-related neonatal genotypes during the first trimester of pregnancy. Limited data is provided to support the hypothesis that the solar cycle predicts folate-related human embryo loss: 379 neonates born at latitude 54°N between 1998 and 2000 were examined for three folate-sensitive, epigenome-related polymorphisms, with solar activity for trimester one accessed via the Royal Greenwich Observatory-US Air force/National Oceanic and Atmospheric Administration Sunspot Database (34,110 total observation days).

Pharmacokinetics of imiquimod 3.75% cream applied daily for 3 weeks to actinic keratoses on the face and/or balding scalp.

Imiquimod 3.75% cream is a topical formulation of imiquimod intended for daily application to treat actinic keratoses of the entire face or balding scalp. The objective of the study was to characterize serum imiquimod and metabolite pharmacokinetics.

Shell clamping behaviour in the limpet Cellana tramoserica.

The behaviour of clamping the shell against the substratum may play an important role in the limpet adhesion mechanism because friction generated by this behaviour resists dislodgement by shear forces. This paper describes the development of an apparatus to analyse limpet clamping activity in relation to known forces, including simulated wave activity and predator attack. The results show that Cellana tramoserica clamps its shell in a closely regulated manner consistent with an active role in the limpet adhesion mechanism.