Calmodulin binding is required for calcium mediated TRPA1 desensitization.

Calcium (Ca) ions affect nearly all aspects of biology. Excessive Ca entry is cytotoxic and Ca-mobilizing receptors have evolved diverse mechanisms for tight regulation that often include Calmodulin (CaM). TRPA1, an essential Ca-permeable ion channel involved in pain signaling and inflammation, exhibits complex Ca regulation with initial channel potentiation followed by rapid desensitization.

Refining the definition of miliary/disseminated tuberculosis in Canada.

Objectives: Although a "multisite" definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein, we sought to generate that evidence.

Methods: We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively diagnosed patients with tuberculosis (TB) in Canada.

Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention.

High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial.

Background: Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT.

The association between phylogenetic lineage and the subclinical phenotype of pulmonary tuberculosis: A retrospective 2-cohort study.

Background: Subclinical pulmonary tuberculosis (PTB) is an asymptomatic disease state between established TB infection and symptomatic (clinical) TB disease. It is present in 20-25% of PTB patients in high-income countries. Mycobacterium tuberculosis complex (MTBC) genetic heterogeneity, and differential host immunological responses, have been implicated in its pathogenesis.

Minor tranquillizers for short-term treatment of newly onset symptoms of anxiety and distress: a systematic review with network meta-analysis of randomized trials.

Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a treatment option when non-pharmacological interventions are insufficient or unavailable. We conducted a systematic review with network meta-analysis of the evidence for short-term (1-4 weeks) pharmacological treatment of newly onset symptoms of anxiety and distress.

The Effects of Exercise during Pregnancy on Gestational Diabetes Mellitus, Preeclampsia, and Spontaneous Abortion among Healthy Women-A Systematic Review and Meta-Analysis.

The aim was to compare the effects of different exercise modalities (aerobic, resistance, aerobic and resistance combined, or mind-body exercise) on gestational diabetes mellitus (GDM), preeclampsia, spontaneous abortion, withdrawal from the study, and adverse events in healthy pregnant women. A systematic search was conducted in February 2022 using MEDLINE, EMBASE, Cochrane library, and SPORT Discus to identify eligible randomized trials. The meta-analysis of 18 studies that examined exercise compared to no exercise showed a reduced risk of GDM (RR: 0.

Factors influencing functioning after volar locking plate fixation of distal radius fractures: a scoping review of 148 studies.

Background And Purpose: A better understanding of factors that influence functioning may improve the identification of patients with distal radius fractures (DRFs) who need hand therapy. The purpose of this scoping review was to provide a comprehensive overview of factors that have been evaluated for their influence on hand functioning following volar plate fixation of DRFs.

Material And Methods: 6 databases were searched from 2005 to 2021 for publications regarding surgical treatment for a DRF with a volar locking plate.

Molecular mechanism of hyperactivation conferred by a truncation of TRPA1.

A drastic TRPA1 mutant (R919*) identified in CRAMPT syndrome patients has not been mechanistically characterized. Here, we show that the R919* mutant confers hyperactivity when co-expressed with wild type (WT) TRPA1. Using functional and biochemical assays, we reveal that the R919* mutant co-assembles with WT TRPA1 subunits into heteromeric channels in heterologous cells that are functional at the plasma membrane.

Effect of melatonin cream on acute radiation dermatitis in patients with primary breast cancer: A double-blind, randomized, placebo-controlled trial.

Aim: This was a double-blind, placebo-controlled randomized study investigating whether melatonin can protect against radiation dermatitis in women receiving radiation therapy for primary breast cancer.

Methods: Patients were included before radiation therapy and followed once weekly throughout treatment with a 3-week follow-up. Patients applied 1 g of cream to the irradiated skin twice daily, consisting of either 25 mg/g melatonin and 150 mg/g dimethyl sulfoxide, or placebo.

The state of tuberculosis surveillance in Canada.

Tuberculosis incidence in Canada has remained essentially unchanged over the past decade. A strategic plan to reduce the burden of disease, underpinned by high-quality surveillance data, is sorely needed. However, tuberculosis surveillance data are lacking in Canada for multiple reasons.

The prevalence, risk factors, and public health consequences of peripheral lymph node-associated clinical and subclinical pulmonary tuberculosis.

Objectives: Relatively little is known about the prevalence, risk factors, and public health consequences of peripheral lymph node (PLN)-associated pulmonary tuberculosis (PTB).

Methods: We developed a 10-year (2010-2019) population-based cohort of PLNTB patients in Canada. We used systematically collected primary source data and expert reader chest radiograph interpretations in a multivariable logistic regression to determine associations between sputum culture positivity and demographic, clinical, and radiographic features.

Quality-of-life outcomes following topical melatonin application against acute radiation dermatitis in patients with early breast cancer: A double-blind, randomized, placebo-controlled trial.

The aim of this double-blind, placebo-controlled, randomized study was to investigate whether topical melatonin administered during radiation therapy could increase the quality of life in patients with primary breast cancer. Patients were followed from the first radiation fraction until 3 weeks after the last. The patients applied 1 g of cream to the irradiated area of the skin twice daily, consisting of either 25 mg/g melatonin and 150 mg/g dimethyl sulfoxide, or a placebo cream.

A comparison of the chest radiographic and computed tomographic features of subclinical pulmonary tuberculosis.

Subclinical pulmonary tuberculosis (PTB) is a recently described intermediate state of great interest, but about which little is known. This study sought to describe and compare the frequency of key radiologic features of subclinical PTB on chest radiograph (CXR) versus computed tomographic scan (CT), and to interpret the clinical and public health relevance of the differences. Diagnostic CXRs and CT scans of the thorax and neck in a 16-year cohort of subclinical PTB patients in Canada were re-acquired and read by two independent readers and arbitrated by a third reader.

Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1.

RAD51 is a critical recombinase that functions in concert with auxiliary mediator proteins to direct the homologous recombination (HR) DNA repair pathway. We show that Cys319 RAD51 possesses nucleophilic characteristics and is important for irradiation-induced RAD51 foci formation and resistance to inhibitors of poly (ADP-ribose) polymerase (PARP). We have previously identified that cysteine (Cys) oxidation of proteins can be important for activity and modulated via binding to peroxiredoxin 1 (PRDX1).

Exome Sequencing Identifies Genetic Variants Associated with Extreme Manifestations of the Cardiovascular Phenotype in Marfan Syndrome.

Marfan Syndrome (MFS) is an autosomal dominant condition caused by variants in the fibrillin-1 () gene. Cardinal features of MFS include ectopia lentis (EL), musculoskeletal features and aortic root aneurysm and dissection. Although dissection of the ascending aorta is the main cause of mortality in MFS, the clinical course differs considerably in age of onset and severity, even among individuals who share the same causative variant, suggesting the existence of additional genetic variants that modify the severity of the cardiovascular phenotype in MFS.

The Radiographic and Mycobacteriologic Correlates of Subclinical Pulmonary TB in Canada: A Retrospective Cohort Study.

Background: Very little is known about subclinical pulmonary TB (PTB), a recently described intermediate state, in high-income countries.

Research Question: What is the prevalence of subclinical PTB in Canada? What are its diagnostic chest radiography features? What is the relationship between those features and time to culture positivity, and what is the association between DNA fingerprint clustering, a measure of local transmission, and radiographic or other features in the foreign-born?

Study Design And Methods: We used primary source data to identify a 16-year retrospective cohort of patients with PTB. Demographic and mycobacteriologic features in patients with subclinical and clinical disease were compared, and the reason for assessment of patients with subclinical disease was described.

How much do smear-negative patients really contribute to tuberculosis transmissions? Re-examining an old question with new tools.

Background: Sputum smear microscopy is a common surrogate for tuberculosis infectiousness. Previous estimates that smear-negative patients contribute 13-20% of transmissions and are, on average, 20 to 25% as infectious as smear-positive cases are understood to be high. Herein, we use an ideal real-world setting, a comprehensive dataset, and new high-resolution techniques to more accurately estimate the true transmission risk of smear-negative cases.

Maternal and neonatal outcomes of COVID-19 in a high-risk pregnant cohort with and without HIV.

Background: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously.

Objectives: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV.

Methods: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020.

[Redefining the gold standard for aortic valve replacement: Minimally invasive with accelerated recovery].

Background: Despite being introduced 20 years ago minimally invasive aortic valve replacement is only performed routinely in a minority of patients world-wide.

Aim: To report the operative outcome of minimally invasive aortic valve replacement done through a partial upper sternotomy.

Patients And Methods: Retrospective analysis of data recorded prospectively of 450 consecutive patients with a median age of 66 years (59% males) who had a minimally invasive aortic replacement.

On the crystal structure and optical spectroscopy of rare earth comprising quaternary tungstates LiBaRE(WO) (RE = La-Nd, Sm-Ho).

The quaternary tungstates Li3Ba2RE3(WO4)8 (RE = La-Nd, Sm-Ho) were obtained by a ceramic synthesis route and were characterized by powder and single crystal X-ray diffraction. The structures of Li3Ba2Pr3(WO4)8 and Li3Ba2Tb3(WO4)8 were refined from single crystal diffractometer data: RbLiBi2(MoO4)4 type, space group C2/c, a = 528.57(2), b = 1292.

Individual and public health consequences associated with a missed diagnosis of pulmonary tuberculosis in the emergency department: A retrospective cohort study.

Objectives: To determine: i) the emergency department (ED) utilization history of pulmonary tuberculosis (PTB) patients, and ii) the potential individual and public health consequences of a missed diagnosis of PTB in this setting.

Design: Retrospective observational cohort study.

Participants: Patients with PTB aged >16 years diagnosed between April 1, 2010 and December 31, 2016 in the Province of Alberta, Canada.

Observations on Glucose Excursions With the Use of a Simple Protocol for Insulin, Following Antenatal Betamethasone Administration.

Aims: Pregnant women with diabetes often require preterm delivery. Antenatal betamethasone reduces perinatal morbidity and mortality, but induces hyperglycemia. The primary objective was to observe glucose excursions and determine the preliminary safety of a protocol for subcutaneous insulin following betamethasone administration in an antenatal ward.

Local Transmission Plays No Important Role in the Occurrence of Multidrug-Resistant Tuberculosis in Immigrants to Canada: An In-depth Epidemiologic Analysis.

Background: Multidrug-resistant (MDR) tuberculosis has increased among migrants in Canada. The cause(s) of this increase is unknown.

Methods: We performed a retrospective cohort study in a Canadian province with substantially increased immigration between 1982-2001 and 2002-2019.

Variation in abdominal wall closure techniques in lower transverse incisions: a nationwide survey across specialties.

Purpose: Lower transverse abdominal incisions are typically used by obstetricians/gynecologists and colorectal surgeons. The suture technique and choice of material when closing the abdomen is an essential factor to decrease the risk of incisional hernia. We conducted a nationwide survey among obstetricians/gynecologists and colorectal surgeons investigating the surgical handling of the fascia, rectus muscle, subcutis, peritoneum, and skin, in lower transverse incisions.