Single cell glucose-stimulated insulin secretion assay using nanowell-in-microwell plates.

Pancreatic β cells secrete insulin in response to elevated levels of glucose. Stem cell derived β (SCβ) cells aim to replicate this glucose-stimulated insulin secretion (GSIS) function, but current preparations cannot provide the same level of insulin as natural β cells. Here, we develop an assay to measure GSIS at the single cell level to investigate the functional heterogeneity of SCβ cells and donor-derived islet cells.

Impact of Virtual Care on Outpatient Urinary Tract Infection Management.

Objective: To examine the effect of virtual care on urine testing, antibiotic prescription patterns, and outcomes of care in urinary tract infection (UTI) management.

Methods: We conducted retrospective analysis of adults treated for UTI in an ambulatory setting across a large health system from March 2020-2021. Outcomes included urine testing, antibiotic prescription, and retreatment or hospitalization, stratified by in-person vs virtual visit.

Impacts on tundra vegetation from heavy metal-enriched fugitive dust on National Park Service lands along the Red Dog Mine haul road, Alaska.

The DeLong Mountain Transportation System (DMTS) haul road links the Red Dog Mine-one of the world's largest zinc mines-with a shipping port on the Chukchi Sea in northwest Alaska, USA. The road traverses 32 km of National Park Service (NPS) lands managed by Cape Krusenstern National Monument (CAKR). Fugitive dusts from ore concentrate transport and mining operations have dispersed zinc (Zn), lead (Pb), cadmium (Cd), and metal sulfides onto NPS lands since the mine began operating in 1989.

Image-based phenotyping of disaggregated cells using deep learning.

The ability to phenotype cells is fundamentally important in biological research and medicine. Current methods rely primarily on fluorescence labeling of specific markers. However, there are many situations where this approach is unavailable or undesirable.

The Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study.

Background: Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses.

Methods: Exceptional response was defined as partial (PR) or complete (CR) response to a systemic treatment with population PR or CR rate less than 10% or an unusually long response (eg, duration >3 times published median).

Detection of Bovine Antibodies against a Conserved Capsid Epitope as the Basis of a Novel Universal Serological Test for Foot-and-Mouth Disease.

Diagnostic tests for foot-and-mouth disease (FMD) include the detection of antibodies against either the viral nonstructural proteins or the capsid. The detection of antibodies against the structural proteins (SP) of the capsid can be used to monitor seroconversion in both infected and vaccinated animals. However, SP tests need to be tailored to the individual FMD virus (FMDV) serotype and their sensitivity may be affected by antigenic variability within each serotype and mismatching between test reagents.

Solid-state nanopore fabrication by automated controlled breakdown.

Solid-state nanopores are now well established as single-biomolecule sensors that hold great promise as sensing elements in diagnostic and sequencing applications. However, until recently this promise has been limited by the expensive, labor-intensive, and low-yield methods used to fabricate low-noise and precisely sized pores. To address this problem, we pioneered a low-cost and scalable solid-state nanopore fabrication method, termed controlled breakdown (CBD), which is rapidly becoming the method of choice for fabricating solid-state nanopores.

Use of an epiphytic lichen and a novel geostatistical approach to evaluate spatial and temporal changes in atmospheric deposition in the Athabasca Oil Sands Region, Alberta, Canada.

Temporal and spatial atmospheric deposition trends of elements to the boreal forest surrounding bitumen production operations in the Athabasca Oil Sands Region (AOSR), Alberta, Canada were investigated as part of a long-term lichen bioindicator study. The study focused on eight elements (sulfur, nitrogen, aluminum, calcium, iron, nickel, strontium, vanadium) that were previously identified as tracers for the major oil sand production sources. Samples of the in situ epiphytic lichen Hypogymnia physodes were collected in 2002, 2004, 2008, 2011, 2014, and 2017 within a ~150 km radius from the center of surface oil sand production operations in the AOSR.

Generation and characterisation of recombinant FMDV antibodies: Applications for advancing diagnostic and laboratory assays.

Foot-and-mouth disease (FMD) affects economically important livestock and is one of the most contagious viral diseases. The most commonly used FMD diagnostic assay is a sandwich ELISA. However, the main disadvantage of this ELISA is that it requires anti-FMD virus (FMDV) serotype-specific antibodies raised in small animals.

Casting Protocols Following BoNT-A Injections to Treat Spastic Hypertonia of the Triceps Surae in Children with Cerebral Palsy and Equinus Gait: A Randomized Controlled Trial.

Aim: To study the effects of single versus serial casting post-Botulinum toxin A (BoNT-A) injections on hypoextensibility of triceps surae in children, 2-7 years old, with cerebral palsy and equinus gait.

Methods: A randomized, stratified, parallel, two-group trial was conducted at a pediatric health center with assessments at baseline, precast, postcast and, 1-, 2-, and 6-month follow-ups. One week following BoNT-A injections into triceps surae muscle, a single below-knee cast (n = 10) or 3 serial casts (n = 10) were applied for 3 weeks.

Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies.

In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lb, from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner.

The Cellular Chaperone Heat Shock Protein 90 Is Required for Foot-and-Mouth Disease Virus Capsid Precursor Processing and Assembly of Capsid Pentamers.

Productive picornavirus infection requires the hijacking of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein, and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerization of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and posttranslational modification of the capsid precursor (P1-2A) by viral and cellular enzymes and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation.

Truncated Bovine Integrin Alpha-v/Beta-6 as a Universal Capture Ligand for FMD Diagnosis.

Foot-and-mouth disease (FMD) is endemic in many regions of the world and is one of the most prevalent epizootic animal diseases. FMD affects livestock, such as cattle, sheep, goats and pigs, and causes enormous economic losses due to reduced productivity and trade restrictions. Preparedness and early diagnosis are essential for effective control of FMD.

Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases.

Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles.

Use of automated reminder letters to improve diabetes management in primary care: outcomes of a quality improvement initiative.

Background: Effective management of patients with diabetes mellitus (DM) can be time-consuming and costly. One patient-centred quality improvement strategy is to generate reminder letters to prompt patient action(s), but this strategy's effect on DM outcomes is uncertain.

Aim: To determine whether using the electronic medical record to automatically generate reminder letters for patients not meeting recommended DM targets is associated with improvement in practice level quality metrics for DM management.

A role for endoplasmic reticulum exit sites in foot-and-mouth disease virus infection.

Picornaviruses replicate their genomes in association with cellular membranes. While enteroviruses are believed to utilize membranes of the early secretory pathway, the origin of the membranes used by foot-and-mouth disease virus (FMDV) for replication are unknown. Secretory-vesicle traffic through the early secretory pathway is mediated by the sequential acquisition of two distinct membrane coat complexes, COPII and COPI, and requires the coordinated actions of Sar1, Arf1 and Rab proteins.

Positively charged residues at the five-fold symmetry axis of cell culture-adapted foot-and-mouth disease virus permit novel receptor interactions.

Field isolates of foot-and-mouth disease virus (FMDV) have a restricted cell tropism which is limited by the need for certain RGD-dependent integrin receptors. In contrast, cell culture-adapted viruses use heparan sulfate (HS) or other unidentified molecules as receptors to initiate infection. Here, we report several novel findings resulting from cell culture adaptation of FMDV.

An infectious recombinant foot-and-mouth disease virus expressing a fluorescent marker protein.

Foot-and-mouth disease virus (FMDV) is one of the most extensively studied animal pathogens because it remains a major threat to livestock economies worldwide. However, the dynamics of FMDV infection are still poorly understood. The application of reverse genetics provides the opportunity to generate molecular tools to further dissect the FMDV life cycle.

Foot-and-mouth disease virus induces autophagosomes during cell entry via a class III phosphatidylinositol 3-kinase-independent pathway.

Autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses to lysosomes for degradation or can be beneficial for viruses by providing specialized membranes for virus replication. Here, we show that the picornavirus foot-and-mouth disease virus (FMDV) induces the formation of autophagosomes. Induction was dependent on Atg5, involved processing of LC3 to LC3II, and led to a redistribution of LC3 from the cytosol to punctate vesicles indicative of authentic autophagosomes.

Beers criteria for potentially inappropriate medication use in older adults.

Nurses can decrease the risk of adverse drug problems with medication review and prompt interventions. The Beers Criteria lists medications to avoid using among elderly clients. The origin of the Beers Criteria, its 2002 modification, and application in acute care settings are explained.

Capsid proteins from field strains of foot-and-mouth disease virus confer a pathogenic phenotype in cattle on an attenuated, cell-culture-adapted virus.

Chimeric foot-and-mouth disease viruses (FMDVs) have been generated from plasmids containing full-length FMDV cDNAs and characterized. The parental virus cDNA was derived from the cell-culture-adapted O1Kaufbeuren B64 (O1K B64) strain. Chimeric viruses, containing capsid coding sequences derived from the O/UKG/34/2001 or A/Turkey 2/2006 field viruses, were constructed using the backbone from the O1K B64 cDNA, and viable viruses (O1K/O-UKG and O1K/A-Tur, respectively) were successfully rescued in each case.

Extracorporeal membrane oxygenation in a Scottish intensive care unit.

I reflected on the training I had on an extraordinary treatment for profound respiratory failure. The result of training enabled us to successfully treat a young female with the influenza A virus with extracorporeal membrane oxygenation (ECMO). I report the positive outcome that occurred, while continuing to run a busy general intensive care unit (ICU).

A dominant-negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus: implications for virus entry.

Foot-and-mouth disease virus (FMDV) can use a number of different integrins (alphavbeta1, alphavbeta3, alphavbeta6, and alphavbeta8) as receptors to initiate infection. Infection mediated by alphavbeta6 is known to occur by clathrin-mediated endocytosis and is dependent on the acidic pH within endosomes. On internalization, virus is detected rapidly in early endosomes (EE) and subsequently in perinuclear recycling endosomes (PNRE), but not in late endosomal compartments.