A continuous mode of action of nitric oxide in hard-to-heal wound healing.

Nitric oxide (NO) is one of the most studied molecules in medical science. The role of NO as an endogenous regulator of inflammation, as an antibacterial agent and as an endogenous gasotransmitter is well established. Even so, despite a plethora of excellent wound healing data, hard-to-heal (chronic) wounds are of epidemic proportions, and still growing in number.

Inbreeding avoidance and cost in a small, isolated trout population.

The persistence of small populations is influenced by the degree and cost of inbreeding, with the degree of inbreeding depending on whether close-kin mating is passively or actively avoided. Few studies have simultaneously studied these factors. We examined inbreeding in a small, isolated population of westslope cutthroat trout using extensive genetic and demographic data.

Olezarsen, a liver-directed ASO therapy for hypertriglyceridemia.

Introduction: Apolipoprotein (apo)C-III, a key regulator of plasma triglyceride (TG) levels, is a prime candidate for the treatment of hypertriglyceridemia (HTG), prevention of acute pancreatitis, and reduction of future atherosclerotic cardiovascular disease (ASCVD) events.

Areas Covered: We discuss the role of apoC-III as a therapeutic target for HTG, describe the pharmacodynamics, pharmacokinetics, and metabolism of olezarsen, as well as report on the findings of recent clinical trials with this liver-directed antisense oligonucleotide (ASO).

Expert Opinion: Olezarsen, a GalNac-conjugated ASO targeting apoC-III, can reduce TG levels by ~ 50% in patients with extreme HTG due to familial chylomicronemia syndrome, as well as in patients with moderate HTG.

Hyperammonaemia: review of the pathophysiology, aetiology and investigation.

Acute hyperammonaemia is a medical emergency as it can progress to cerebral oedema, seizures, coma and death. Hepatic encephalopathy secondary to cirrhotic disease or portosystemic shunting are relatively well-known causes, but non-cirrhotic aetiologies of acute hyperammonaemia are less well-known, especially in the emergency department. However, an elevated ammonia is not required to make the diagnosis of hepatic encephalopathy.

Democratizing Artificial Intelligence in Anatomic Pathology.

Context.—: Artificial intelligence is a transforming technology for anatomic pathology. Involvement within the workforce will foster support for algorithm development and implementation.

Cascade testing of children and adolescents for elevated Lp(a) in pedigrees with familial hypercholesterolaemia.

Elevated plasma lipoprotein(a) [Lp(a)] is a common, inherited condition independently causing cardiovascular disease. Recent expert recommendations suggest opportunistically testing for elevated Lp(a) during cascade testing for familial hypercholesterolaemia (FH). We investigated the effectiveness of detecting elevated Lp(a) in 103 children and adolescents who were first-degree relatives of 66 adult index FH cases as part of an established FH cascade screening program.

Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease of prematurity with limited treatment options. To uncover biomarkers of BPD risk, this study investigated epigenetic and transcriptomic signatures of prematurity at birth and during the neonatal period at day 14 and 28. Peripheral blood DNAs from preterm infants were applied to methylation arrays and cell-type composition was estimated by deconvolution.

Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome.

Context: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease.

Objective: (1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss.

Epigenomic profiling of isolated blood cell types reveals highly specific B cell smoking signatures and links to disease risk.

Background: Tobacco smoking alters the DNA methylation profiles of immune cells which may underpin some of the pathogenesis of smoking-associated diseases. To link smoking-driven epigenetic effects in specific immune cell types with disease risk, we isolated six leukocyte subtypes, CD14+ monocytes, CD15+ granulocytes, CD19+ B cells, CD4+ T cells, CD8+ T cells, and CD56+ natural killer cells, from whole blood of 67 healthy adult smokers and 74 nonsmokers for epigenome-wide association study (EWAS) using Illumina 450k and EPIC methylation arrays.

Results: Numbers of smoking-associated differentially methylated sites (smCpGs) at genome-wide significance (p < 1.

The Adrenal Vein Sampling Outcomes Study (AVOS): success rates following adrenalectomy for unilateral primary aldosteronism.

The objective was to determine the clinical and biochemical success rates and assess the nature of follow-up after adrenalectomy in patients with unilateral primary aldosteronism (PA), subtyped by adrenal vein sampling (AVS) in West Australia (WA) using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Clinical and biochemical outcomes were retrospectively evaluated in patients with unilateral PA who underwent adrenalectomy according to AVS between September 2017 and September 2020. Pre- and post-surgical data were collected using a standardised questionnaire, review of clinic letters and examination of private and public pathology results and radiological reports.

Lipid-lowering therapies and cardiovascular risk-stratification strategies in adults with type 1 diabetes.

Purpose Of Review: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality in adults with type 1 diabetes (T1D). Although dyslipidaemia is a modifiable and prevalent risk factor in individuals with T1D, determining when to initiate lipid-lowering therapy for primary prevention of ASCVD can be challenging. In this article, recommendations for lipid-lowering therapy from updated clinical guidelines over the last 5 years, additional risk-stratification methods, hypertriglyceridaemia management and potential barriers to optimal care in adults with T1D are discussed.

A variant in the fibronectin (FN1) gene, rs1250229-T, is associated with decreased risk of coronary artery disease in familial hypercholesterolaemia.

Background: Increased risk of coronary artery disease (CAD) in familial hypercholesterolaemia (FH) is modified by factors beyond defects in the low-density lipoprotein receptor pathway. The rs1250229-T single nucleotide polymorphism (SNP) in the FN1 gene is associated with CAD in genome-wide association studies and is in linkage disequilibrium with another SNP (rs1250259-T) in FN1 that is associated with decrease fibronectin secretion.

Objective: We investigated whether rs1250229-T was also associated with prevalent CAD in patients with genetically confirmed FH.

Attainment of Lipid Targets Following Coronary Artery Bypass Graft Surgery: Can We Do Better?

Objective: Patients undergoing coronary artery bypass graft (CABG) surgery remain at high cardiovascular risk; however, few studies have evaluated lipid management and attainment of lipid targets in these patients. We investigated the proportion of CABG surgery patients who attained low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) targets.

Methods: Data were retrospectively obtained from patients undergoing CABG surgery at an Australian tertiary hospital between February 2015 and August 2020.

Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program.

Background: Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD.

Age-specific survival rates, causes of death, and allowable take of golden eagles in the western United States.

In the United States, the Bald and Golden Eagle Protection Act prohibits take of golden eagles (Aquila chrysaetos) unless authorized by permit, and stipulates that all permitted take must be sustainable. Golden eagles are unintentionally killed in conjunction with many lawful activities (e.g.

Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance.

Summary: We report a case of an 11-year-old girl presenting with a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene. This case highlights that INSR gene variants can be a cause for monogenic diabetes in children and adolescents and the need for genetic evaluation in atypical presentations of diabetes. We also describe the possible role of metformin in treating individuals with type A insulin resistance syndrome due to INSR gene variants.

Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey.

Background: Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs (miRs) maintain cellular homeostasis and may regulate the response to environmental stress.

Objectives: We tested the hypothesis that specific miRs are associated with liver disease and PCB exposures in a residential cohort.