Interventions in an Ambulatory Setting to Prevent Progression to Severe Disease in Patients With COVID-19: A Systematic Review.

Objective: To conduct a systematic review on the effectiveness and safety of pharmacological and nonpharmacological interventions, in the ambulatory setting, aimed at preventing severe disease in patients with COVID-19.

Data Sources: Electronic databases (PubMed, EMBASE, and EuropePMC) were searched on January 6, 2021.

Study Selection And Data Extraction: A systematic review was conducted, adhering to PRISMA guidelines.

Inhibition of Histone Deacetylases 1, 2, and 3 Enhances Clearance of Cholesterol Accumulation in Niemann-Pick C1 Fibroblasts.

Niemann-Pick disease type C1 (NPC1) is a rare genetic cholesterol storage disorder caused by mutations in the gene. Mutations in this transmembrane late endosome protein lead to loss of normal cholesterol efflux from late endosomes and lysosomes. It has been shown that broad spectrum histone deacetylase inhibitors (HDACi's) such as Vorinostat correct the cholesterol accumulation phenotype in the majority of NPC1 mutants tested in cultured cells.

Characterising mental health and addictions and assault-related health care use in the year prior to death: a population-based linked cohort study of homicide victims.

Introduction: Homicide is an important cause of death for older youth and adult Canadians; however, little is known about health care use prior to death among this population.

Objectives: To characterise health care use for mental health and addictions (MHA) and serious assault (herein referred to assault) one year prior to death among individuals who died by homicide in Ontario, Canada using linked mortality and health care utilisation data.

Methods: We report rates of health care use for MHA and assault in the year prior to death among all individuals 16 years and older in Ontario, Canada, who died by homicide from April 2003 to December 2012 (N = 1,541).

Development of One-Step Non-Solvent Extraction and Sensitive UHPLC-MS/MS Method for Assessment of N-(n-Butyl) Thiophosphoric Triamide (NBPT) and N-(n-Butyl) Phosphoric Triamide (NBPTo) in Milk.

N-(n-butyl) thiophosphoric triamide (NBPT) is a urease inhibitor utilised in urea-based fertilizers. In Ireland, fertilizer treated with NBPT is applied to pasture to mitigate both ammonia and nitrous oxide emissions, but concerns arise as to the potential for residues in milk products. A quick ultrafiltration extraction and ultra-high performance liquid chromatography coupled with mass spectrometry triple quadrupole (UHPLC-MS/MS) quantitation method was developed and validated in this study.

Development and proposed evaluation of an eHealth learning tool for undergraduate university students in Ireland.

Undergraduate university students are at a critical stage of development in terms of their academic, social, psychological and behavioural health. Patterns established during these formative years can last a lifetime. eHealth tools have the potential to be engaging, convenient and accessible to a wide range of students by providing health information and enhancing the uptake of positive health behaviours.

Quantifying the risk of SARS-CoV-2 reinfection over time.

Despite over 140 million SARS-CoV-2 infections worldwide since the beginning of the pandemic, relatively few confirmed cases of SARS-CoV-2 reinfection have been reported. While immunity from SARS-CoV-2 infection is probable, at least in the short term, few studies have quantified the reinfection risk. To our knowledge, this is the first systematic review to synthesise the evidence on the risk of SARS-CoV-2 reinfection over time.

A rapid review of measures to support people in isolation or quarantine during the Covid-19 pandemic and the effectiveness of such measures.

This rapid review aimed to identify measures available to support those in isolation or quarantine during the coronavirus disease 2019 (Covid-19) pandemic, and determine their effectiveness in improving adherence to these recommendations and or reducing transmission. The rapid review consisted of two elements, the first was a review of guidance published by national and international agencies relating to measures to support those in isolation (due to case status) or quarantine (due to close contact status) during the Covid-19 pandemic. Five categories of support measures were identified in the international guidance, they were: Psychological, addiction and safety supports, Essential supplies, Financial aid, Information provision and Enforcement.

Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.

PIM kinases are constitutively active proto-oncogenic serine/threonine kinases that play a role in cell cycle progression, metabolism, inflammation and drug resistance. PIM kinases interact with and stabilize p53, c-Myc and parallel signaling pathway PI3K/Akt. This study evaluated PIM kinase expression in NSCLC and in response to PI3K/mTOR inhibition.

Compound Climate and Infrastructure Events: How Electrical Grid Failure Alters Heat Wave Risk.

The potential for critical infrastructure failures during extreme weather events is rising. Major electrical grid failure or "blackout" events in the United States, those with a duration of at least 1 h and impacting 50,000 or more utility customers, increased by more than 60% over the most recent 5 year reporting period. When such blackout events coincide in time with heat wave conditions, population exposures to extreme heat both outside and within buildings can reach dangerously high levels as mechanical air conditioning systems become inoperable.

A case report of microsatellite instability (MSI)-high, amplified pancreatic adenocarcinoma with central nervous system metastasis.

Pancreatic adenocarcinoma commonly presents as metastatic disease and harbors a dire prognosis due to its aggressive behavior, propensity for resistance to therapies, and lack of targetable driver mutations. Additionally, despite advances in other cancers, immunotherapy has been ineffective in this disease thus far and treatment remains centered around cytotoxic chemotherapy. Here, we present a case of a patient with pancreatic adenocarcinoma harboring both high microsatellite instability (MSI-H) and amplification.

Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.

Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer.

Linking statistical shape models and simulated function in the healthy adult human heart.

Cardiac anatomy plays a crucial role in determining cardiac function. However, there is a poor understanding of how specific and localised anatomical changes affect different cardiac functional outputs. In this work, we test the hypothesis that in a statistical shape model (SSM), the modes that are most relevant for describing anatomy are also most important for determining the output of cardiac electromechanics simulations.

COVID-19-Induced Anosmia and Ageusia Are Associated With Younger Age and Lower Blood Eosinophil Counts.

Background: Anosmia and ageusia are symptoms commonly associated with COVID-19, but the relationship with disease severity, onset and recovery are unclear.

Objective: To examine factors associated with anosmia and ageusia and the recovery from these symptoms in an ethnically diverse cohort.

Methods: Individuals tested for SARS-CoV-2 between March and April 2020 were eligible for the study.

Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort.

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major cause of infant morbidity and mortality. Inflammation is an important component in the physiopathologic pathway leading to PTB but results from cross-sectional studies on associations between inflammation, as measured by cytokines, and PTB are inconsistent. Timing of cytokine measurement during pregnancy varies between studies and may contribute to inconsistent findings.

Outcomes for gastrostomy-fed children and their parents: qualitative findings from the 'Your Tube' study.

Aim: To identify child and parent outcomes relevant to having a gastrostomy, and to specify outcomes believed to be particularly salient to type of diet (formula vs blended food).

Method: Twenty parents, two children (both 12y), and 41 professionals (dietitians [n=10]; nurses [n=12]; paediatricians [n=12]; speech and language therapists [n=7)]) were recruited. Parents and children were interviewed; professionals participated in focus groups.

Estimating Population Benefits of Prevention Approaches Using a Risk Tool: High Resource Users in Ontario, Canada.

Background: Healthcare spending is concentrated, with a minority of the population accounting for the majority of healthcare costs.

Methods: The authors modelled the impact of high resource user (HRU) prevention strategies within five years using the validated High Resource User Population Risk Tool.

Results: The authors estimated 758,000 new HRUs in Ontario from 2013-2014 to 2018-2019, resulting in $16.

OpenEP: A Cross-Platform Electroanatomic Mapping Data Format and Analysis Platform for Electrophysiology Research.

Background: Electroanatomic mapping systems are used to support electrophysiology research. Data exported from these systems is stored in proprietary formats which are challenging to access and storage-space inefficient. No previous work has made available an open-source platform for parsing and interrogating this data in a standardized format.

ERF4 and MYB52 transcription factors play antagonistic roles in regulating homogalacturonan de-methylesterification in Arabidopsis seed coat mucilage.

Homogalacturonan (HG), a component of pectin, is synthesized in the Golgi apparatus in its fully methylesterified form. It is then secreted into the apoplast where it is typically de-methylesterified by pectin methylesterases (PME). Secretion and de-esterification are critical for normal pectin function, yet the underlying transcriptional regulation mechanisms remain largely unknown.

Cross species multi-omics reveals cell wall sequestration and elevated global transcript abundance as mechanisms of boron tolerance in plants.

Boron toxicity is a world-wide problem for crops, yet we have a limited understanding of the genetic responses and adaptive mechanisms to this stress in plants. We employed a cross-species comparison between boron stress-sensitive Arabidopsis thaliana and its boron stress-tolerant extremophyte relative Schrenkiella parvula, and a multi-omics approach integrating genomics, transcriptomics, metabolomics and ionomics to assess plant responses and adaptations to boron stress. Schrenkiella parvula maintains lower concentrations of total boron and free boric acid than Arabidopsis when grown with excess boron.

A National Registry Study of Patient and Renal Survival in Adult Nephrotic Syndrome.

Introduction: We aimed to determine the mortality rate, cause of death, and rate of end-stage kidney disease (ESKD) in adults with nephrotic syndrome (NS).

Methods: We conducted a national registry-based study, including all 522 adults who had a kidney biopsy for NS in Scotland in 2014-2017. We linked the Scottish Renal Registry to death certificate data.

NK cells in antibody-mediated rejection - Key effector cells in microvascular graft damage.

Antibody-mediated rejection (ABMR) stands as the major limitation to long-term transplant outcome. The immunologic understanding of ABMR continues to progress and has identified natural killer (NK) cells as key effector cells promoting and coordinating the immune attack on the graft microvascular endothelium. This review discusses the current concepts outlining the different ways that allow for NK cell recognition of graft endothelial cells which includes antibody-dependent as well as independent processes.