BMP and STRA8 act collaboratively to ensure correct mitotic-to-meiotic transition in the fetal mouse ovary.

A successful mitosis-to-meiosis transition in germ cells is essential for fertility in sexually reproducing organisms. In mice and humans, it is established that expression of STRA8 is critical for meiotic onset in both sexes. Here we show that BMP signalling is also essential, not for STRA8 induction but for correct meiotic progression in female mouse fetal germ cells.

Qualitative findings from North America's first drug compassion club.

In Canada, the ongoing fatal overdose crisis remains driven by the unpredictable potency and content of the illicit drug supply. From August 2022 until October 2023, the Drug User Liberation Front [DULF] operated a drug compassion club [CC], which sells drugs of known composition and purity without medical oversight. The present study is a qualitative evaluation of this project.

Perinatal exposure to environmental chemicals that disrupt thyroid function can perturb testis development.

Thyroid hormones (THs) are essential for normal growth and development. Their role in skeletal and brain development is well established, with congenital hypothyroidism causing stunted growth and severe intellectual disability. THs are also important for the development of other tissues and organs, including the testis.

Road to Recovery: protocol for a mixed-methods prospective cohort study evaluating the impact of a new model of substance use care in a Canadian setting.

Introduction: The Road to Recovery (R2R) Initiative is an innovative model of substance use care that seeks to increase treatment capacity by creating approximately 100 new addiction treatment beds to provide on-demand addiction care in Vancouver, British Columbia, for patients with substance use disorders. The new model also coordinates the region's existing clinical substance use services to support patients across a care continuum that includes traditional office-based addiction treatment and harm reduction services, early withdrawal management and more intensive abstinence-based treatment programming. To understand the impact of offering on-demand and coordinated substance use care, an observational cohort of individuals who access any R2R clinical service will be created to examine health and social outcomes over time.

'I'm on the coast and I'm on methadone': A qualitative study examining access to opioid agonist treatment in rural and coastal British Columbia.

Introduction: Despite rural regions being disproportionately impacted by the toxic drug supply, little is known about the contextual factors influencing access to opioid agonist treatment (OAT) specific to rural residents. The present study examines these factors in a rural and coastal setting in British Columbia, Canada.

Methods: The qualitative methods were used to examine the barriers and facilitators to OAT access.

An integrated curriculum for dentists and dental therapists in Liverpool.

The role of the dental therapist has evolved over the course of the past 70 years, both in the UK and across the globe. The General Dental Council's Scope of practice guidance sets out the skills and abilities of each of the professional roles within the dental team, including the dental therapist. Scope of practice of the multidisciplinary team remains poorly understood, to the detriment of teamworking.

Reasons for Enrolling in Safer Supply Programs: A Longitudinal Qualitative Study on Participant Goals and Related Outcomes in the MySafe Program.

Objective: Safer supply programs are a novel response to the ongoing overdose crisis in Canada--providing people at high overdose risk with a safer alternative to the highly toxic unregulated drug supply. The MySafe program provides pharmaceutical-grade opioids to participants via biometric dispensing machines. This study examines program-related goals and related outcomes across time.

Coronary artery fistula following surgical myectomy for hypertrophic obstructive cardiomyopathy: a case report.

Background: Coronary artery fistula is a rare, but recognized complication of surgical myectomy. Although most communicate with the right heart, a large fistula into the left ventricular cavity may result in a shunt haemodynamically analogous to aortic regurgitation. Understanding the variable presentation of iatrogenic coronary fistulae and the optimal evaluation strategy is critical to obtaining a timely diagnosis and instituting treatment.

Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

Purpose: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).

Methods: In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS).

Female-specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and estrogen receptor α.

Little is known of the brain mechanisms that mediate sex-specific autism symptoms. Here, we demonstrate that deletion of the autism spectrum disorder (ASD)-risk gene, Pten, in neocortical pyramidal neurons (Pten knockout [KO]) results in robust cortical circuit hyperexcitability selectively in female mice observed as prolonged spontaneous persistent activity states. Circuit hyperexcitability in females is mediated by metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor α (ERα) signaling to mitogen-activated protein kinases (Erk1/2) and de novo protein synthesis.

Media framing xylazine as a "zombie drug" is amplifying stigma onto people who use drugs.

Amid increasing efforts to understand xylazine-associated harms, examining the potentially catastrophic role of stigma resulting from media outlets framing xylazine as the "zombie drug" is imperative. Zombies are cinematically depicted as soulless, dangerous, and required to be killed off entirely for public safety, making the "zombie" analogy especially grave amid the fatal overdose crisis. Xylazine is called the "zombie drug" due to its heavy sedative effect and associated-severely infected skin ulcers.

Vibrational Circular Dichroism Spectroscopy with a Classical Polarizable Force Field: Alanine in the Gas and Condensed Phases.

Polarizable force fields are an essential component for the chemically accurate modeling of complex molecular systems with a significant degree of fluxionality, beyond harmonic or perturbative approximations. In this contribution we examine the performance of such an approach for the vibrational spectroscopy of the alanine amino acid, in the gas and condensed phases, from the Fourier transform of appropriate time correlation functions generated along molecular dynamics (MD) trajectories. While the infrared (IR) spectrum only requires the electric dipole moment, the vibrational circular dichroism (VCD) spectrum further requires knowledge of the magnetic dipole moment, for which we provide relevant expressions to be used with polarizable force fields.

A qualitative assessment of tablet injectable opioid agonist therapy (TiOAT) in rural and smaller urban British Columbia, Canada: Motivations and initial impacts.

Background: The evolving and unpredictable unregulated drug market has driven an unprecedented overdose crisis that requires effective intervention. Growing evidence suggests that novel opioid agonist treatments, such as tablet injectable opioid agonist therapy (TiOAT), have potential to prevent overdoses and other drug-related harms. More evidence is needed to characterize their utility in achieving these outcomes.

Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

Background: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm.

Objectives: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism.

A nationwide serological survey for Dirofilaria immitis in companion cats in the United States of America: 3.5% antibody and 0.3% antigen positivity.

Background: Feline heartworm disease (HWD) is a complex and often misdiagnosed disease in cats, caused by the filarial nematode Dirofilaria immitis. Despite its significant impact, studies reporting the prevalence of D. immitis in apparently healthy pet cats in the USA are lacking.

Female specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and Estrogen Receptor α.

Autism manifests differently in males and females and the brain mechanisms that mediate these sex-dependent differences are unknown. Here, we demonstrate that deletion of the ASD-risk gene, in neocortical pyramidal neurons (NSE KO) results in robust hyperexcitability of local neocortical circuits in female, but not male, mice, observed as prolonged, spontaneous persistent activity states (UP states). Circuit hyperexcitability in NSE KO mice is mediated by enhanced and/or altered signaling of metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor α (ERα) to ERK and protein synthesis selectively in deleted female neurons.

Challenges of implementing safer supply programs in Canada during the COVID-19 pandemic: A qualitative analysis.

Background: Canada is experiencing an unprecedented drug toxicity crisis driven by a highly toxic unregulated drug supply contaminated with fentanyl, benzodiazepine, and other drugs. Safer supply pilot programs provide prescribed doses of pharmaceutical alternatives to individuals accessing the unregulated drug supply and have been implemented to prevent overdose and reduce related harms. Given the recent emergence of these pilot programs and the paucity of data on implementation challenges, we sought to document challenges in their initial implementation phase.

Isolation and Culture Techniques for Fetal Mouse Germ Cells.

The fetal gonad contains a great variety of differentiating cell populations, of which germ cells make up a relatively small percentage. In order to study germ cell-specific gene and protein expression, as well as determine direct effects of signaling molecules, it is necessary to prepare enriched populations of germ cells and maintain them in culture for several hours to multiple days. The protocols in this chapter are designed to provide a guide for the isolation or enrichment of primordial germ cells (from 9.

Using Technology to Enhance Community Health and Territorial Resources Access.

Improving access to health information and territorial resources can be a way to help strengthen health-related quality of life perception in disadvantaged communities. We argue that, in countries facing diverse economic and social disparities and challenges, technology can be leveraged to improve communities' access to evidence-based, up-to-date, comprehensive, and culturally appropriate supportive territorial resources, thereby improving individuals' quality of life, especially for those living with one or more chronic diseases. This paper discusses the benefits of introducing and designing a user-friendly, relevant, and effective web-based technology to broaden patients' access to healthcare resources and tailored health information, supporting community-based quality of life transformation.

Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects.

Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development.

Disease-related stigma among people who inject drugs in Toronto amidst the COVID-19 pandemic.

Background: Stigma overwhelmingly affects people who inject drugs. The COVID-19 pandemic posed unique challenges for people who inject drugs, who are already stigmatized as being "dangerous and spreading disease." The present study explored ways in which stigma was experienced by a sample of people who inject drugs in Toronto, Canada following COVID-related public health precaution measures.