A case of disseminated blastomycosis in New England.

infections are classified as dimorphic fungal infections commonly seen geographically throughout the Mississippi and Ohio River Valleys, St. Laurence Seaways, as well as the Canadian providences of Ontario Manitoba, and Saskatchewan. Although primarily endemic in the Midwestern United States, there has been a rise in cases throughout New England.

Development of compounds for targeted degradation of mammalian cryptochrome proteins.

The mammalian cryptochrome proteins (CRY1 and CRY2) are transcriptional repressors most notable for their role in circadian transcriptional feedback. Not all circadian rhythms depend on CRY proteins, however, and the CRY proteins are promiscuous interactors that also regulate many other processes. In cells with chronic CRY deficiency, protein homeostasis is highly perturbed, with a basal increase in cellular stress and activation of key inflammatory signalling pathways.

Orthogonal validation of PROTAC mediated degradation of the integral membrane proteins EGFR and c-MET.

Dysregulation of integral membrane proteins (IMPs) has been linked to a myriad of diseases, making these proteins an attractive target in drug research. Whilst PROTAC technology has had a significant impact in scientific research, its application to IMPs is still limited. Limitations of the traditional approach of immunoblotting in PROTAC research include the low throughput compared to other methods, as well as a lack of spatial information for the target.

The therapeutic role of exercise training during menopause for reducing vascular disease.

Menopause marks a major milestone in female reproductive ageing. It is characterized by the cessation of ovarian function and a concomitant decline in hormones such as oestradiol. Subsequently, females undergoing menopausal transition experience a progressive increase in cardiovascular and cerebrovascular disease risk.

Characterizing vascular and hormonal changes in women across the life span: a cross-sectional analysis.

Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, is a nontraditional risk factor that precedes the development of cardiovascular disease (CVD). However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. Women free from major disease were enrolled across the adult life span (aged 18-70 yr, = 140).

Inducing Receptor Degradation as a Novel Approach to Target CC Chemokine Receptor 2 (CCR2).

CC chemokine receptor 2 (CCR2) has been linked to many inflammatory and immune diseases, making it a relevant drug target. Yet, all CCR2 antagonists developed so far have failed in clinical trials; thus, novel strategies are needed to target this receptor. Targeted protein degradation represents a novel approach to inhibit protein function by hijacking the cellular degradation machinery, such as the proteasome, to degrade the protein of interest.

Gonadal status modulates large elastic artery stiffness in healthy middle-aged and older men.

Hypogonadism is a risk factor for cardiovascular disease (CVD) in men related, in part, to increased oxidative stress. Elevated large artery stiffness and central pulsatile hemodynamics (e.g.

An Innovative Course on Involving Patients in Health Professions Education.

Background & Need For Innovation: Patients can be actively involved in various aspects of health professions education (HPE). However, learners in HPE graduate programs have minimal opportunities to learn how to involve patients in HPE.

Steps Taken For Development And Implementation Of Innovation: We designed, implemented, and evaluated a 12-week asynchronous, online graduate course that provides learners such opportunities.

Insulin sensitivity, body composition and bone mineral density after testosterone treatment in transgender youth with and without prior GnRH agonist therapy.

Background: 1.8% of youth identify as transgender; a growing proportion are transgender male (female sex, male gender identity). Many receive gonadotropin releasing hormone agonist (GnRHa) therapy to suppress endogenous puberty and/or will start testosterone to induce secondary sex characteristics that align with gender identity.

The association of gender-affirming hormone therapy duration and body mass index on bone mineral density in gender diverse adults.

Introduction: Feminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT's impact on BMD, but the association of BMI and BMD in TGD adults deserves further study.

Objective: To determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults.

[Improving pre-emptive access to the kidney transplant waiting list between 2017 and 2021: assessment of a regional program in Aquitaine].

Introduction: Pre-emptive access to the kidney transplant (KT) waiting list remains limited in France, with only 3.9% of patients on pre-emptive KT and 5.6% of patients registered at the time of initiation of dialysis.

Impact of Switching From Immediate- or Prolonged-Release to Once-Daily Extended-Release Tacrolimus (LCPT) on Tremor in Stable Kidney Transplant Recipients: The Observational ELIT Study.

Once-daily extended-release tacrolimus (LCPT) exhibits increased bioavailability versus immediate-release (IR-TAC) and prolonged release (PR-TAC) tacrolimus. Improvements in tremor were previously reported in a limited number of kidney transplant patients who switched to LCPT. We conducted a non-interventional, non-randomized, uncontrolled, longitudinal, prospective, multicenter study to assess the impact of switching to LCPT on tremor and quality of life (QoL) in a larger population of stable kidney transplant patients.

Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity.

Bone Density in Transgender Youth on Gender-Affirming Hormone Therapy.

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.

Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX).

Extending social accountability mandates to biomedical research in Canadian faculties of medicine.

Background: Social accountability (SA), as defined by Boelen and Heck, is the obligation of medical schools to address the needs of communities through education, research and service activities. While SA is embedded within health profession education frameworks in medicine, they are rarely taught within graduate-level (MSc/PhD) education.

Methods: As these programs train future medical researchers, we invited first-year graduate students enrolled in a mandatory professionalism class at our institution ( = 111) to complete a survey on their perceptions of the importance of SA in their research, training, and future careers.

Sex Differences in Association of Physical Activity With All-Cause and Cardiovascular Mortality.

Background: Although physical activity is widely recommended for reducing cardiovascular and all-cause mortality risks, female individuals consistently lag behind male individuals in exercise engagement.

Objectives: The goal of this study was to evaluate whether physical activity derived health benefits may differ by sex.

Methods: In a prospective study of 412,413 U.

A Medical Education Research Library: key research topics and associated experts.

When clinician-educators and medical education researchers use and discuss medical education research, they can advance innovation in medical education as well as improve its quality. To facilitate the use and discussions of medical education research, we created a prefatory visual representation of key medical education research topics and associated experts. We conducted one-on-one virtual interviews with medical education journal editorial board members to identify what they perceived as key medical education research topics as well as who they associated, as experts, with each of the identified topics.

RlmQ: a newly discovered rRNA modification enzyme bridging RNA modification and virulence traits in .

rRNA modifications play crucial roles in fine-tuning the delicate balance between translation speed and accuracy, yet the underlying mechanisms remain elusive. Comparative analyses of the rRNA modifications in taxonomically distant bacteria could help define their general, as well as species-specific, roles. In this study, we identified a new methyltransferase, RlmQ, in responsible for the Gram-positive specific mG2601, which is not modified in (G2574).

Measurement of the Immunosuppressant Possession Ratio by Transplant Clinical Pharmacists Captures a Non-Adherence Associated With Antibody-Mediated Rejection.

Our objective was to calculate an immunosuppressant possession ratio (IPR) to diagnose non-adherence at the time of antibody-mediated rejection (ABMR). IPR was defined as the ratio of number of pills collected at the pharmacy to the number of pills prescribed over a defined period. In a first cohort of 91 kidney transplant recipients (KTRs), those with an IPR < 90% had more frequently a tacrolimus through level coefficient of variation >30% than patients with an IPR = 100% (66.