Negative Impact of COVID-19 Associated Health System Shutdown on Patients Diagnosed With Colorectal Cancer: A Retrospective Study From a Large Tertiary Center in Ontario, Canada.

Background: In March 2020, a directive to halt all elective and non-urgent procedures was issued in Ontario, Canada because of COVID-19. The directive caused a temporary slowdown of screening programs including surveillance colonoscopies for colorectal cancer (CRC). Our goal was to determine if there was a difference in patient and tumour characteristics between CRC patients treated surgically prior to the COVID-19 directive compared to CRC patients treated after the slowdown.

Motor Band Sign in Motor Neuron Disease: A Marker for Upper Motor Neuron Involvement.

Background And Objective: The prevalence and role of the motor band sign (MBS) remain unclear in motor neuron disease. We report the frequency of MBS in amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), its correlation with clinical upper motor neuron (UMN) signs, and prognostic value in ALS.

Methods: We conducted a retrospective study of ALS, PLS, and controls with retrievable MRI between 2010 and 2018.

Implanted spinal neuromodulation interventions for chronic pain in adults.

Background: Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity.

Empire-CF study: A phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis.

Background: Cystic fibrosis (CF) is characterized by neutrophilic inflammation in the airways. Leukotriene B4 (LTB) is a neutrophil chemoattractant and has been implicated in CF pathogenesis. Acebilustat, a novel, synthetic, small-molecule leukotriene A4 hydrolase inhibitor, reduces LTB production.

Can Achilles tendon xanthoma be distinguished from Achilles tendinopathy using Dixon method MRI? A cross-sectional exploratory study.

Background: Familial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture.

Identification of novel genes involved in apoptosis of HIV-infected macrophages using unbiased genome-wide screening.

Background: Macrophages, besides resting latently infected CD4+ T cells, constitute the predominant stable, major non-T cell HIV reservoirs. Therefore, it is essential to eliminate both latently infected CD4+ T cells and tissue macrophages to completely eradicate HIV in patients. Until now, most of the research focus is directed towards eliminating latently infected CD4+ T cells.

The impact of providing personalized depression risk information on self-help and help-seeking behaviors: Results from a mixed methods randomized controlled trial.

Objectives: To evaluate the impact of providing personalized depression risk information on self-help and help-seeking behaviors among individuals who are at high risk of having a major depressive episode (MDE).

Materials And Methods: In a mixed methods randomized controlled trial, participants who were at high risk of having a MDE, were recruited from across Canada, and were randomized into intervention (n = 358) and control (n = 354) groups. Participants in the intervention group received their personalized depression risk estimated by sex-specific risk prediction models for MDE.

A Quality Improvement Intervention to Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) in Patients With Chronic Kidney Disease: Clinical Research Protocol of a Cluster-Randomized Clinical Trial.

Background: Many patients with kidney failure will live longer and healthier lives if they receive a kidney transplant rather than dialysis. However, multiple barriers prevent patients from accessing this treatment option.

Objective: To determine if a quality improvement intervention provided in chronic kidney disease (CKD) programs (vs.

Chromatin Remodeling in the Brain-a evelopmental Odyssey.

During brain development, the genome must be repeatedly reconfigured in order to facilitate neuronal and glial differentiation. A host of chromatin remodeling complexes facilitates this process. At the genetic level, the non-redundancy of these complexes suggests that neurodevelopment may require a lexicon of remodelers with different specificities and activities.

Pharmacokinetic modeling of dynamic contrast-enhanced (DCE)-MRI in PI-RADS category 3 peripheral zone lesions: preliminary study evaluating DCE-MRI as an imaging biomarker for detection of clinically significant prostate cancers.

Purpose: To determine if pharmacokinetic modeling of DCE-MRI can diagnose CS-PCa in PI-RADS category 3 PZ lesions with subjective negative DCE-MRI.

Materials And Methods: In the present IRB approved, bi-institutional, retrospective, case-control study, we identified 73 men with 73 PZ PI-RADS version 2.1 category 3 lesions with MRI-directed-TRUS-guided targeted biopsy yielding: 12 PZ CS-PCa (ISUP Grade Group 2; N = 9, ISUP 3; N = 3), 27 ISUP 1 PCa and 34 benign lesions.

Publication by association: how the COVID-19 pandemic has shown relationships between authors and editorial board members in the field of infectious diseases.

During the COVID-19 pandemic, the rush to scientific and political judgements on the merits of hydroxychloroquine was fuelled by dubious papers which may have been published because the authors were not independent from the practices of the journals in which they appeared. This example leads us to consider a new type of illegitimate publishing entity, 'self-promotion journals' which could be deployed to serve the instrumentalisation of productivity-based metrics, with a ripple effect on decisions about promotion, tenure and grant funding, but also on the quality of manuscripts that are disseminated to the medical community and form the foundation of evidence-based medicine.

PKCα-mediated phosphorylation of the diacylglycerol kinase ζ MARCKS domain switches cell migration modes by regulating interactions with Rac1 and RhoA.

Cells can switch between Rac1 (lamellipodia-based) and RhoA (blebbing-based) migration modes, but the molecular mechanisms regulating this shift are not fully understood. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, forms independent complexes with Rac1 and RhoA, selectively dissociating each from their common inhibitor RhoGDI. DGKζ catalytic activity is required for Rac1 dissociation but is dispensable for RhoA dissociation; instead, DGKζ stimulates RhoA release via a kinase-independent scaffolding mechanism.

A Casz1-NuRD complex regulates temporal identity transitions in neural progenitors.

Neural progenitor cells undergo identity transitions during development to ensure the generation different types of neurons and glia in the correct sequence and proportions. A number of temporal identity factors that control these transitions in progenitor competence have been identified, but the molecular mechanisms underlying their function remain unclear. Here, we asked how Casz1, the mammalian orthologue of Drosophila castor, regulates competence during retinal development.

Impact of Pretransplant and New-Onset Diabetes After Transplantation on the Risk of Major Adverse Cardiovascular Events in Kidney Transplant Recipients: A Population-based Cohort Study.

Background: Pretransplant diabetes and new-onset diabetes after transplant (NODAT) are known risk factors for vascular events after kidney transplantation, but the incidence and magnitude of the risk of major adverse cardiovascular events (MACE) and cardiac deaths remain uncertain in recent era.

Methods: A population cohort study of kidney transplant recipients identified using data from linked administrative healthcare databases from Ontario, Canada. The incidence rates of MACE (expressed as events with 95% confidence interval [95% CI] per 1000 person-years were reported according to diabetes status of pretransplant diabetes, NODAT, or no diabetes.

Metabolic gestational age assessment in low resource settings: a validation protocol.

Preterm birth is the leading global cause of neonatal morbidity and mortality. Reliable gestational age estimates are useful for quantifying population burdens of preterm birth and informing allocation of resources to address the problem. However, evaluating gestational age in low-resource settings can be challenging, particularly in places where access to ultrasound is limited.

Lower plasma PCSK9 in normocholesterolemic subjects is associated with upregulated adipose tissue surface-expression of LDLR and CD36 and NLRP3 inflammasome.

Background: LDL-cholesterol lowering variants that upregulate receptor uptake of LDL, such as in PCSK9 and HMGCR, are associated with diabetes via unclear mechanisms. Activation of the NLRP3 inflammasome/interleukin-1 beta (IL-1β) pathway promotes white adipose tissue (WAT) dysfunction and type 2 diabetes (T2D) and is regulated by LDL receptors (LDLR and CD36). We hypothesized that: (a) normocholesterolemic subjects with lower plasma PCSK9, identifying those with higher WAT surface-expression of LDLR and CD36, have higher activation of WAT NLRP3 inflammasome and T2D risk factors, and; (b) LDL upregulate adipocyte NLRP3 inflammasome and inhibit adipocyte function.

Opinion and practice survey about the use of prognostic models in acute pulmonary embolism.

Introduction: Methods for prognosis assessment and patient management in acute pulmonary embolism (PE) are much debated among physicians. We conducted an online survey to determine physician's attitudes and barriers towards the use of prognostic models when treating patients with acute PE.

Method: Physicians members of the French and the European scientific societies for emergency medicine or of a French thrombosis research network were reached by their respective scientific societies and invited to participate via email.

Process evaluation of an implementation trial to improve the triage, treatment and transfer of stroke patients in emergency departments (T trial): a qualitative study.

Background: The implementation of evidence-based protocols for stroke management in the emergency department (ED) for the appropriate triage, administration of tissue plasminogen activator to eligible patients, management of fever, hyperglycaemia and swallowing, and prompt transfer to a stroke unit were evaluated in an Australian cluster-randomised trial (T trial) conducted at 26 emergency departments. There was no reduction in 90-day death or dependency nor improved processes of ED care. We conducted an a priori planned process influential factors that impacted upon protocol uptake.

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days.

: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases.

White Adipose Tissue Surface Expression of LDLR and CD36 is Associated with Risk Factors for Type 2 Diabetes in Adults with Obesity.

Objective: Human conditions with upregulated receptor uptake of low-density lipoproteins (LDL) are associated with diabetes risk, the reasons for which remain unexplored. LDL induce metabolic dysfunction in murine adipocytes. Thus, it was hypothesized that white adipose tissue (WAT) surface expression of LDL receptor (LDLR) and/or CD36 is associated with WAT and systemic metabolic dysfunction.

Mindfulness-based stress reduction alters brain activity for breast cancer survivors with chronic neuropathic pain: preliminary evidence from resting-state fMRI.

Purpose: Breast cancer continues to be the most commonly diagnosed cancer among Canadian women, with as many as 25-60% of women suffering from chronic neuropathic pain (CNP) as a pervasive consequence of treatment. While pharmacological interventions have shown limited efficacy for the management of CNP to date, psychological interventions, such as mindfulness-based stress reduction (MBSR), may be a promising alterative for improving pain-related problems. The purpose of this study was to use brain imaging methods to investigate this potential.

Measuring organizational context in Australian emergency departments and its impact on stroke care and patient outcomes.

Background: Emergency departments (ED) are challenging environments but critical for early management of patients with stroke.

Purpose: To identify how context affects the provision of stroke care in 26 Australian EDs.

Method: Nurses perceptions of ED context was assessed with the Alberta Context Tool.

Simultaneous glomerular filtration rate determination using inulin, iohexol, and Tc-DTPA demonstrates the need for customized measurement protocols.

Urinary inulin clearance is considered the gold standard of glomerular filtration rate (GFR) measurement but plasma clearance of less expensive and more accessible tracers is more commonly performed. Many plasma sampling protocols exist but little is known about their accuracy. Here, the study objectives were to compare plasma iohexol and Tc-DTPA GFR with varying sampling strategies to the GFR measured by urinary inulin and to identify protocols with the greatest accuracy according to clinical characteristics.