Markedly Elevated Citrulline in a Neonate: Citrin Deficiency due to a Previously Unreported Solute Carrier Family 25 Member 13 Variant.

Background: Citrin deficiency (CD) is an autosomal recessive metabolic disorder affecting the urea cycle and energy production. Diagnosis involves measuring ammonia and amino acid levels (eg: citrulline), with confirmation through solute carrier family 25 member 13 (SLC25A13) gene mutation analysis. Herein, we present a case report of a variant in the SLC25A13 gene that has not been previously reported in the literature.

Recent Recall of Iron Reagent-Investigation of Potential Reagent Contamination and Assay Improvement Strategy.

Background: Recently, a major manufacturer recalled several lots of iron assay reagent due to positive bias of roughly 15%-30% and the cause remains unknown. This study investigated the root cause of this positive bias and evaluated a simple practical approach to improve the assay.

Methods: Performance comparison of recalled and unimpacted iron assay kits was done utilizing calibrators, quality control (QC) materials, and 42 remnant patient samples.

Elevated C5-hydroxy acylcarnitine in an infant girl as a result of holocarboxylase synthetase deficiency.

Context: Elevated 3-hydroxyisovaleryl-/2-methyl-3-hydroxybutyryl (C5-OH) acylcarnitine in blood can result from several genetic enzyme deficiencies: 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy 3-methylglutaryl-CoA lyase deficiency, beta-ketothiolase deficiency, 2-methyl 3-hydroxybutyryl-CoA dehydrogenase deficiency, primary 3-methylglutaconic aciduria, multiple biotin-dependent carboxylase deficiencies and biotin metabolism disorders. Biochemical tests help differentiate these causes while molecular tests are usually required for definitive diagnosis.

Case Description: We reported an infant girl with newborn screen findings of elevated C5-OH acylcarnitine.

Newborn Screening: Current Practice and Our Journey over the Last 60 Years.

Background: Inborn errors of metabolism comprise a set of more than 2000 known disorders which can result in significant morbidity and may be rapidly fatal. Diagnosing these disorders at birth and treating immediately, however, may often result in a normal to near-normal life for the affected infant. Thus, newborn screening (NBS) has saved or improved the lives of countless individuals since its inception in the 1960s.

Identification of Potential Plant-Derived Pancreatic Beta-Cell-Directed Agents Using New Custom-Designed Screening Method: as an Example.

Background: Folk medicines are attractive therapeutic agents for treating type 2 diabetes mellitus (T2DM). Most plant extracts that have been suggested to restore β-cells function were tested in vivo. Some only have been tested in vitro to determine whether they have a direct effect on β-cells islets of Langerhans.

Mouse islet-derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function.

Aims: Evidence is accumulating of the therapeutic benefits of mesenchymal stromal cells (MSCs) in diabetes-related conditions. We have identified a novel population of stromal cells within islets of Langerhans - islet stellate cells (ISCs) - which have a similar morphology to MSCs. In this study we characterize mouse ISCs and compare their morphology and function to MSCs to determine whether ISCs may also have therapeutic potential in diabetes.

Statistically significant differences versus convincing evidence of real treatment effects: an analysis of the false positive risk for single-centre trials in anaesthesia.

Background: The American Statistical Association has highlighted problems with null hypothesis significance testing and outlined alternative approaches that may 'supplement or even replace P-values'. One alternative is to report the false positive risk (FPR), which quantifies the chance the null hypothesis is true when the result is statistically significant.

Methods: We reviewed single-centre, randomised trials in 10 anaesthesia journals over 6 yr where differences in a primary binary outcome were statistically significant.

Kisspeptin upregulates β-cell serotonin production during pregnancy.

During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. The lactogenic hormones are well established to play a key role in regulating the islet adaptation to pregnancy, and one of the mechanisms through which they act is through upregulating β-cell serotonin production. During pregnancy islet serotonin levels are significantly elevated, where it is released from the β-cells to drive the adaptive response through paracrine and autocrine effects.

Interpreting frequentist hypothesis tests: insights from Bayesian inference.

Randomized controlled trials are one of the best ways of quantifying the effectiveness of medical interventions. Therefore, when the authors of a randomized superiority trial report that differences in the primary outcome between the intervention group and the control group are "significant" (i.e.

Mesenchymal stromal cell secretory molecules improve the functional survival of human islets.

Aims: Human islet transplantation as a therapy for type 1 diabetes is compromised by the loss of functional beta cells in the immediate post-transplantation period. Mesenchymal stromal cells (MSCs) and MSC-derived secretory peptides improve the outcomes of islet transplantation in rodent models of diabetes. Here, we utilized a mouse model for human islet transplantation and assessed the effects of a cocktail of MSC-secreted peptides (screened by MSC-secretome for human islet GPCRs) on the functional survival of human islets.

Defining major surgical complications using administrative data in Ontario: a validation study.

Background: Although surgical complications are often included as an outcome of surgical research conducted using administrative data, little validation work has been performed. We sought to evaluate the diagnostic performance of an algorithm designed to capture major surgical complications using health administrative data.

Methods: This retrospective study included patients who underwent high-risk elective general surgery at a single institution in Ontario, Canada, from Sept.

Utility of Commercially Available Quantitative hCG Immunoassays as Tumor Markers in Trophoblastic and Non-Trophoblastic Disease.

Background: The use of quantitative human chorionic gonadotropin (hCG) as a tumor marker is widely accepted despite lack of FDA-approval for oncology. Differences in iso- and glycoform recognition among hCG immunoassays is well established, exhibiting wide inter-method variability. Here, we assess the utility of 5 quantitative hCG immunoassays for use as tumor markers in trophoblastic and non-trophoblastic disease.

Phage-Like Microvirus Genome Sequence Identified in Wastewater in Arizona, USA, in November 2020 Encodes an Endolysin and a Putative Multiheme Cytochrome -like Protein.

We describe the genome (4,696 nucleotides [GC content, 56%; coverage, 3,641×) of MAZ-Nov-2020, a microvirus identified from municipal wastewater in Maricopa County, Arizona, USA, in November 2020. The MAZ-Nov-2020 genome encodes major capsid protein, endolysin, replication initiator protein, and two hypothetical proteins, one of which was predicted to likely be a membrane-associated multiheme cytochrome .

The Switch and Reciprocating Models for the Function of ABC Multidrug Exporters: Perspectives on Recent Research.

ATP-binding cassette (ABC) transporters comprise a large superfamily of primary active transporters, which are integral membrane proteins that couple energy to the uphill vectorial transport of substrates across cellular membranes, with concomitant hydrolysis of ATP. ABC transporters are found in all living organisms, coordinating mostly import in prokaryotes and export in eukaryotes. Unlike the highly conserved nucleotide binding domains (NBDs), sequence conservation in the transmembrane domains (TMDs) is low, with their divergent nature likely reflecting a need to accommodate a wide range of substrate types in terms of mass and polarity.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery.

Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients.

Design, Setting, And Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021.