Vancomycin Therapeutic Drug Monitoring: A Cross-Sectional Survey of Canadian Hospitals.

Background: Little is known about the current landscape of vancomycin therapeutic drug monitoring (TDM) in Canadian hospitals, which operate within publicly funded health care systems.

Objectives: To determine current TDM practices for vancomycin and associated challenges and to gather perceptions about TDM based on area under the concentration-time curve (AUC) in Canadian hospitals.

Methods: An electronic survey was distributed to hospital pharmacists in spring 2021 through multiple national and provincial antimicrobial stewardship, public health, and pharmacy organizations.

Baroreflex resetting of human sympathetic action potential subpopulations during exercise.

This study tested the hypothesis that during fatiguing volitional exercise in humans, descending cortical signals and ascending skeletal muscle metaboreflex signals exert divergent control over baroreflex resetting of sympathetic action potential (AP) discharge. We quantified the baroreflex gain for sympathetic AP clusters within the muscle sympathetic nerve activity neurogram (peroneal microneurography and continuous wavelet transform) during baseline (BSL), the first 2-min of a 5-min isometric handgrip (20% of maximal effort; IHG1), the last 2-min of IHG (IHG2), and during postexercise circulatory occlusion (PECO) in seven healthy participants. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability (%) versus diastolic blood pressure (DBP; mmHg) for 10 normalized AP clusters.

Normal and excessive muscle sympathetic nerve activity in heart failure: implications for future trials of therapeutic autonomic modulation.

Aims: Patients with sympathetic excess are those most likely to benefit from novel interventions targeting the autonomic nervous system. To inform such personalized therapy, we identified determinants of augmented muscle sympathetic nerve activity (MSNA) in heart failure, versus healthy controls.

Methods And Results: We compared data acquired in 177 conventionally-treated, stable non-diabetic patients in sinus rhythm, aged 18-79 years (149 males; 28 females; left ventricular ejection fraction [LVEF] 25 ± 11% [mean ± standard deviation]; range 5-60%), and, concurrently, under similar conditions, in 658 healthy, normotensive volunteers (398 males; aged 18-81 years).

Muscle Sympathetic Excitatory Response to Dynamic 1-Leg Cycling in Heart Failure With Preserved Ejection Fraction.

We provide the first description in a patient with heart failure with preserved ejection fraction of the "paradoxical," exaggerated reflex increase in muscle sympathetic nerve activity in the opposite, stationary limb during dynamic 1-leg cycling exercise that was documented previously in patients with reduced ejection fraction. ().

Influence of sex and age on the relationship between aerobic fitness and muscle sympathetic nerve activity in healthy adults.

We examined the influence of sex and age on the relationship between aerobic fitness and muscle sympathetic nerve activity (MSNA) in healthy adults. Data were assessed from 224 volunteers (88 females), aged 18-76 yr, in whom resting MSNA (microneurography) and peak oxygen uptake (V̇o; incremental exercise test) were evaluated. When separated into younger (<50 yr) and older (≥50 yr) subgroups, there were inverse relationships between relative V̇o (mL·kg·min) and MSNA burst frequency in younger males ( = 0.

Imaging Insulin Granule Dynamics in Human Pancreatic β-Cells Using Total Internal Reflection Fluorescence (TIRF) Microscopy.

Due to the ultra-thin optical sectioning capability of exclusively illuminating space at the interface where total internal reflection occurs, the TIRF microscope has been indispensable for monitoring biological processes adjacent to the plasma membrane with excellent signal-to-noise ratio. Insulin-containing granules fuse with the plasma membrane to release contents within hundreds of milliseconds, which involves well-orchestrated assembly of SNARE complex and associated proteins. A video-rate multiple-color TIRF microscope offers the unique opportunity to visualize single secretory granule docking and fusion dynamics and can also map its regulators with high spatiotemporal resolution.

Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome (SQTS) are inherited arrhythmogenic disorders that can cause sudden death. Numerous genes have been reported to cause these conditions, but evidence supporting these gene-disease relationships varies considerably. To ensure appropriate utilization of genetic information for CPVT and SQTS patients, we applied an evidence-based reappraisal of previously reported genes.

Trehalose causes low-grade lysosomal stress to activate TFEB and the autophagy-lysosome biogenesis response.

The autophagy-lysosome system is an important cellular degradation pathway that recycles dysfunctional organelles and cytotoxic protein aggregates. A decline in this system is pathogenic in many human diseases including neurodegenerative disorders, fatty liver disease, and atherosclerosis. Thus there is intense interest in discovering therapeutics aimed at stimulating the autophagy-lysosome system.

E-Survey of Stressors and Protective Factors in Practicing Medical Assistance in Dying.

To better identify, quantify, and understand the current stressors and protective factors reported by Canadian medical assistance in dying (MAiD) assessors and providers to inform policy, education, and supports. E-survey of MAiD stressors ( = 33) and protective factors ( = 27); resilience measurement and comments relating to practice involving physicians and nurse practitioners who provide MAiD services and belong to the Canadian Association of MAiD Assessors and Providers or a francophone equivalent. The survey was conducted, while Parliament was considering changes to MAiD eligibility criteria, which occurred during COVID-19 pandemic restrictions.

Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis?

Objective: Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to ACE2 (angiotensin-converting enzyme 2). While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen.

An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.

Background: Long QT syndrome (LQTS) is the first described and most common inherited arrhythmia. Over the last 25 years, multiple genes have been reported to cause this condition and are routinely tested in patients. Because of dramatic changes in our understanding of human genetic variation, reappraisal of reported genetic causes for LQTS is required.

Days Alive and Out of Hospital: Validation of a Patient-centered Outcome for Perioperative Medicine.

Background: Days alive and out of hospital is a potentially useful patient-centered quality measure for perioperative care in adult surgical patients. However, there has been very limited prior validation of this endpoint with respect to its ability to capture differences in patient-level risk factor profiles and longer-term postoperative outcomes. The main objective of this study was assessment of the feasibility and validity of days alive and out of hospital as a patient-centered outcome for perioperative medicine.

B-Cell Deficiency Lowers Blood Pressure in Mice.

The proto-oncogene c-myb (and corresponding nuclear transcription factor, c-Myb) regulates the proliferation and differentiation of hematologic and vascular smooth muscle cells; however, the role of c-Myb in blood pressure regulation is unknown. Here, we show that mice homozygous for a hypomorphic c-myb allele ( c-myb ) conferring reduced c-Myb activity manifest reduced peripheral blood and kidney B220 B-cells and have decreased systolic (104±2 versus 120±1 mm Hg; P<0.0001) and diastolic blood pressure (71±2 versus 83±1 mm Hg; P<0.