Population perinatal substance use and an environmental scan of health services in British Columbia, Canada.

Background: Substance use during pregnancy is underreported globally and there is limited data on its prevalence and the availability of supportive services. This study determined population perinatal substance use in British Columbia (BC) by region and examined the availability of clinical and community-based programs.

Methods: Using linked provincial health administrative data, we conducted a population-based retrospective cohort study including all BC residents accessing care for substance use (alcohol, opioids, stimulants, sedatives, and cannabis) within 12 months of first perinatal care record to delivery during 2016-2021.

Effects of Internal Stress and Hydrogen Penetration on the Performance of ErO Coatings as Hydrogen Permeation Barriers.

Ceramic coatings that can effectively prevent hydrogen permeation have a wide range of applications in hydrogen energy and nuclear fusion reactors. In this study, for the first time, the internal stress of ErO coatings was found to be a key factor that could determine their hydrogen permeation resistance and lifespan. The internal stress was controlled by designing layered ErO coatings.

Prescribing practices in opioid agonist treatment and changes in compliance to clinical dosing guidelines in British Columbia, Canada.

Background And Aim: In British Columbia, Canada, clinical guidelines for the treatment of opioid use disorders (OUD) were updated in 2017, during a period in which the potency and composition of the illicit drug supply changed rapidly. We aimed to describe changes in opioid agonist treatment (OAT) prescribing practices at the population level in a setting in which fentanyl and its analogs have become the primary illicit opioid of use.

Design, Setting And Participants: This was a population-based retrospective cohort study using three linked health administrative databases in British Columbia (BC), Canada.

Self-objectification and cosmetic surgery consideration among Chinese young women: The mediating roles of alienation and body image inflexibility.

The behavior of undergoing cosmetic surgery is a coping strategy for body-image threats and challenges. Self-objectification is associated with alienation and body image inflexibility, and all of these are associated with stronger cosmetic surgery considerations. This study evaluated the relationship between self-objectification and cosmetic surgery consideration, and whether this relationship was mediated by alienation and body image inflexibility.

From Mo-Si-B to Mo-Ti-Si-B Alloys: A Short Review.

Mo-Si-B alloys have attracted considerable research interest during the last several decades due to their high melting points, excellent high-temperature strength and relatively good oxidation resistance. However, insufficient room-temperature fracture toughness and high-temperature oxidation resistance restrain their further application. Generally, a sufficient volume fraction of BCC-Mo solid-solution phase, providing the ductility, and a high Si content, responsible for the formation of passive oxide scales, is difficult to achieve simultaneously in this ternary system.

Self-induced cobalt-derived hollow structure Prussian blue as a cathode for sodium-ion batteries.

As advanced electrode materials for sodium ion batteries, Prussian blue and its derivatives have attracted considerable attention due to their low cost, structural stability and facile synthesis process. However, the application of commercially available Prussian blue is limited by its poor electronic conductivity as well as the structural defect induced by crystalline/interstitial water molecules. Herein, to address these drawbacks, an etching-agent free method is developed to synthesize Prussian blue with a hollow structure, and the synthesis mechanism is revealed.

Acid-Assisted Ball Mill Synthesis of Carboxyl-Functional-Group-Modified Prussian Blue as Sodium-Ion Battery Cathode.

Prussian blue attracts the attention of many researchers as a promising candidate for use in sodium-ion battery cathodes due to its open frameworks and high working potential. However, the interstitial water in its crystal structure and its poor electronic conductivity limits its performance in practical sodium-ion batteries. Here, acid-assisted ball milling synthesis was employed as a versatile method for the production of surface-modified Prussian blue.

polyaniline coating of Prussian blue as cathode material for sodium-ion battery.

Prussian blue (PB) has great potential for use as a sodium cathode material owing to its high working potential and cube frame structure. Herein, this work reports a two-step method to synthesize PB with ascorbic acid as the ball-milling additive, which improves the electrochemical rate performance of PB during the traditional co-precipitation method. The obtained PB sample exhibited a superior specific capability (113.

Negative Problems Orientation Questionnaire for Chinese Adolescents: Bifactor Model and Measurement Invariance.

The Negative Problem Orientation Questionnaire (NPOQ) is a widely used tool for assessing negative problem orientation (NPO). However, its construct and measurement invariance has not been adequately tested in adolescents. The present study explored the possible construct of the NPOQ and its measurement invariance in a sample of 754 Chinese adolescents (51.

The impact of negative mood state on sleep-related attentional bias in insomnia.

Sleep-related attentional bias is thought to play a role in the maintenance of insomnia. However, this concept has been questioned by several studies that did not show the presence of sleep-related attentional bias in clinical insomnia or poor sleepers. Our goal in the present study was to test whether the mood state of individuals with insomnia affects the presence of sleep-related attentional bias.

Novel flexible Fenton-like catalyst: Unique CuO nanowires arrays on copper mesh with high efficiency across a wide pH range.

Free-standing and flexible Cu@CuO nanowires (NWs) mesh as an easily recycled Fenton-like catalyst is developed for the first time. Dense CuO nanowire arrays were uniformly grown on a copper mesh surface simply by wet etching accompanied with thermal dehydration. These dense CuO NWs provide a large specific area and therefore guarantee excellent catalytic performance toward the degradation of rhodamine B (RhB).

Flexible 3D Fe@VO core-shell mesh: A highly efficient and easy-recycling catalyst for the removal of organic dyes.

Nowadays, it is extremely urgent to search for efficient and effective catalysts for water purification due to the severe worldwide water-contamination crises. Here, 3D Fe@VO core-shell mesh, a highly efficient catalyst toward removal of organic dyes with excellent recycling ability in the dark is designed and developed for the first time. This novel core-shell structure is actually 304 stainless steel mesh coated by VO, fabricated by an electrophoretic deposition method.

Identification of novel bifunctional HIV-1 reverse transcriptase inhibitors.

Objectives: The increasing prevalence of mutations in HIV-1 reverse transcriptase (RT) that confer resistance to existing NRTIs and NNRTIs underscores the need to develop RT inhibitors with novel mode-of-inhibition and distinct resistance profiles.

Methods: Biochemical assays were employed to identify inhibitors of RT activity and characterize their mode of inhibition. The antiviral activity of the inhibitors was assessed by cell-based assays using laboratory HIV-1 isolates and MT4 cells.

Perfectionism and adolescent sleep quality: The mediating role of repetitive negative thinking.

This study explores the mediating effects of repetitive negative thinking in the relationship between perfectionism and adolescent sleep quality. A sample of 1664 Chinese adolescents with a mean age of 15.0 years was recruited, and they completed four measures relating to perfectionism, sleep quality, worry, and rumination.

Parallel patterning of SiO wafer via near-field electrospinning of metallic salts and polymeric solution mixtures.

This paper describes a near-field electrospinning technique combined with heat treatment process used to directly align parallel metal oxide and metal nitride fibers on silicon dioxide substrate. The effects of near-field electrospinning parameters (including collector-to-needle distance, applied voltage and the moving speed of the collector) on the morphology of the resulted fibers have been studied. Metallic salt-contained precursor fibers are individually aligned via near-field electrospinning of metallic salts and polymeric solution mixtures.

Carboxamide Spleen Tyrosine Kinase (Syk) Inhibitors: Leveraging Ground State Interactions To Accelerate Optimization.

Optimization of a series of highly potent and kinome selective carbon-linked carboxamide spleen tyrosine kinase (Syk) inhibitors with favorable drug-like properties is described. A pervasive Ames liability in an analogous nitrogen-linked carboxamide series was obviated by replacement with a carbon-linked moiety. Initial efforts lacked on-target potency, likely due to strain induced between the hinge binding amide and solvent front heterocycle.

Discovery of pyrazolopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia.

Herein, we present the identification of a novel class of pyrazolopyrimidine phosphodiesterase 10A (PDE10A) inhibitors. Beginning with a lead molecule (1) identified through a fragment-based drug discovery (FBDD) effort, lead optimization was enabled by rational design, X-ray crystallography, metabolic and off-target profiling, and fragment scaffold-hopping. We highlight the discovery of PyP-1, a potent, highly selective, and orally bioavailable pyrazolopyrimidine inhibitor of PDE10A.

Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin.

A series of novel substituted-[(3R)-amino-2-(2,5-difluorophenyl)]tetrahydro-2H-pyran analogs have been prepared and evaluated as potent, selective and orally active DPP-4 inhibitors. These efforts lead to the discovery of a long acting DPP-4 inhibitor, omarigliptin (MK-3102), which recently completed phase III clinical development and has been approved in Japan.

Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis.

Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency.

Discovery of [¹¹C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors.

Phosphodiesterase 10A (PDE10A) inhibition has recently been identified as a potential mechanism to treat multiple symptoms that manifest in schizophrenia. In order to facilitate preclinical development and support key proof-of-concept clinical trials of novel PDE10A inhibitors, it is critical to discover positron emission tomography (PET) tracers that enable plasma concentration/PDE10A occupancy relationships to be established across species with structurally diverse PDE10A inhibitors. In this Letter, we describe how a high-throughput screening hit was optimized to provide [(11)C]MK-8193 (8j), a PET tracer that supports the determination of plasma concentration/PDE10A occupancy relationships for structurally diverse series of PDE10A inhibitors in both rat and rhesus monkey.

Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes.

In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.

Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses.

The optimization of a novel series of non-nucleoside reverse transcriptase inhibitors (NNRTI) led to the identification of pyridone 36. In cell cultures, this new NNRTI shows a superior potency profile against a range of wild type and clinically relevant, resistant mutant HIV viruses. The overall favorable preclinical pharmacokinetic profile of 36 led to the prediction of a once daily low dose regimen in human.

In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a mainstay of therapy for treating human immunodeficiency type 1 virus (HIV-1)-infected patients. MK-1439 is a novel NNRTI with a 50% inhibitory concentration (IC50) of 12, 9.7, and 9.

The relationship between worry tendency and sleep quality in Chinese adolescents and young adults: the mediating role of state-trait anxiety.

To investigate the relationship between worry tendency and sleep quality and the mediating effect of state-trait anxiety, 1072 adolescents and young adults from Jiangxi and Fujian Provinces in China were administered questionnaires pertaining to worry tendency, sleep quality, and state-trait anxiety. The results showed significant grade differences for worry tendency, sleep quality, and state-trait anxiety. Worry tendency was negatively associated with sleep quality, which was mediated by state anxiety and trait anxiety.

Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia.

We describe the discovery of potent and orally bioavailable tetrahydropyridopyrimidine inhibitors of phosphodiesterase 10A by systematic optimization of a novel HTS lead. Lead compound THPP-1 exhibits nanomolar potencies, excellent pharmacokinetic properties, and a clean off-target profile. It displays in vivo target engagement as measured by increased rat striatal cGMP levels upon oral dosing.