Determining Plasma Tacrolimus Concentrations Using High-Performance LC-MS/MS in Renal Transplant Recipients.

Background: Whole-blood therapeutic drug monitoring of tacrolimus is conducted to maintain tacrolimus concentrations within a safe and effective range. Changes in hematocrit cause variability in blood concentrations of tacrolimus because it is highly bound to erythrocytes. Measuring plasma concentrations may eliminate this variability; however, current methods have limitations owing to the use of cross-reactive immunoassays, plasma separation at nonbiological temperatures, and lack of clinical validation.

Desmoglein-2 as a cancer modulator: friend or foe?

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer.

Predicting stop codon reassignment improves functional annotation of bacteriophages.

The majority of bacteriophage diversity remains uncharacterised, and new intriguing mechanisms of their biology are being continually described. Members of some phage lineages, such as the , repurpose stop codons to encode an amino acid by using alternate genetic codes. Here, we investigated the prevalence of stop codon reassignment in phage genomes and subsequent impacts on functional annotation.

Hybracter: Enabling Scalable, Automated, Complete and Accurate Bacterial Genome Assemblies.

Improvements in the accuracy and availability of long-read sequencing mean that complete bacterial genomes are now routinely reconstructed using hybrid (i.e. short- and long-reads) assembly approaches.

Enhanced phylogenetic insights into the microbiome of chronic rhinosinusitis through the novel application of long read 16S rRNA gene amplicon sequencing.

Introduction: 16S rRNA next generation sequencing (NGS) has been the de facto standard of microbiome profiling. A limitation of this technology is the inability to accurately assign taxonomy to a species order. Long read 16S sequencing platforms, including Oxford Nanopore Technologies (ONT), have the potential to overcome this limitation.

The risk of fractures after entering long-term care facilities.

Background: Stratifying residents at increased risk for fractures in long-term care facilities (LTCFs) can potentially improve awareness and facilitate the delivery of targeted interventions to reduce risk. Although several fracture risk assessment tools exist, most are not suitable for individuals entering LTCF. Moreover, existing tools do not examine risk profiles of individuals at key periods in their aged care journey, specifically at entry into LTCFs.

Autologous Faecal Microbiota Transplantation to Improve Outcomes of Haematopoietic Stem Cell Transplantation: Results of a Single-Centre Feasibility Study.

Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual's own stool (autologous FMT) to mitigate the risks of disease transmission from a donor stool.

Clinical application of cytokine-induced killer (CIK) cell therapy in colorectal cancer: Current strategies and future challenges.

Colorectal cancer (CRC) remains a significant global health burden and is the second leading cause of cancer-related death. Cytokine induced killer (CIK) cell therapy is an immunotherapy which has the potential to meet this need. Clinical trials of CIK cell therapy for the management of CRC have reported improved clinical outcomes.

Superior efficacy of a skin-applied microprojection device for delivering a novel Zika DNA vaccine.

Zika virus (ZIKV) infections are spreading silently with limited global surveillance in at least 89 countries and territories. There is a pressing need to develop an effective vaccine suitable for equitable distribution globally. Consequently, we previously developed a proprietary DNA vaccine encoding secreted non-structural protein 1 of ZIKV (pVAX-tpaNS1) to elicit rapid protection in a T cell-dependent manner in mice.

The intra-host evolutionary landscape and pathoadaptation of persistent in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common chronic sinonasal mucosal inflammation associated with biofilm and relapsing infections. This study aimed to determine rates of persistence and pathoadaptation in CRS patients by investigating the genomic relatedness and antibiotic resistance/tolerance in longitudinally collected clinical isolates. A total of 68 .

Angina and Non-Obstructive Coronary Artery (ANOCA) Patients with Coronary Vasomotor Disorders.

Angina and Non-Obstructive Coronary Artery (ANOCA) patients often lack a clear explanation for their symptoms, and are frequently discharged with the label of "unspecified chest pain", despite the availability of functional coronary angiography (provocative spasm and microvascular function testing) to identify potential underlying coronary vasomotor disorders. This study compared the outcomes of ANOCA patients with a coronary vasomotor disorder diagnosis post elective coronary angiography to patients discharged with unspecified chest pain. Using the CADOSA (Coronary Angiogram Database of South Australia) registry, consecutive symptomatic patients ( = 7555) from 2012 to 2018 underwent elective angiography; 30% had ANOCA (stenosis <50%).

Euglycemic Ketoacidosis in Two Patients Without Diabetes After Introduction of Sodium-Glucose Cotransporter 2 Inhibitor for Heart Failure With Reduced Ejection Fraction.

Objective: Ketoacidosis induced by sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment has been consistently observed in clinical practice in patients with type 2 diabetes despite minimal indication from the landmark cardiovascular outcome trials. It has been postulated that individuals without diabetes will not develop this complication due to an adequate insulin secretory capacity, which will protect against significant ketone formation. Cardiovascular outcome trials examining SGLT2i use in individuals with heart failure but not diabetes have not reported ketoacidosis.

Molecular Mechanism Biomarkers Predict Diagnosis in Schizophrenia and Schizoaffective Psychosis, with Implications for Treatment.

Diagnostic uncertainty and relapse rates in schizophrenia and schizoaffective disorder are relatively high, indicating the potential involvement of other pathological mechanisms that could serve as diagnostic indicators to be targeted for adjunctive treatment. This study aimed to seek objective evidence of methylenetetrahydrofolate reductase C677T genotype-related bio markers in blood and urine. Vitamin and mineral cofactors related to methylation and indolamine-catecholamine metabolism were investigated.

Saos-2 cells cultured under hypoxia rapidly differentiate to an osteocyte-like stage and support intracellular infection by Staphylococcus aureus.

The intracellular infection of osteocytes represents a clinically important aspect of osteomyelitis. However, few human osteocyte in vitro models exist and the differentiation of immature osteoblasts to an osteocyte stage typically takes at least 4-weeks of culture, making the study of this process challenging and time consuming. The osteosarcoma cell line Saos-2 has proved to be a useful model of human osteoblast to mature osteocyte differentiation.

An exploration of healthcare use in older people waiting for and receiving Australian community-based aged care services.

Aim: Home care packages (HCPs) facilitate older individuals to remain at home, with longer HCP wait times associated with increased mortality risk. We analyze healthcare cost data pre- and post-HCP access to inform hypotheses around the effects of healthcare use and mortality risk.

Methods: Regression models were used to assess the impact of delayed HCP access on healthcare costs and to compare costs whilst waiting and in the 6- and 12 month periods post-HCP access for 16 629 older adults.

Assessment and management of diabetes-related foot infection according to the new International Working Group on the Diabetic Foot guidelines 2023-Multidisciplinary grand rounds.

Diabetes-related foot disease is a serious and common complication for people with diabetes mellitus. The gold standard care for a person with diabetes-related foot disease is the involvement of a multidisciplinary foot team engaged in evidence-based care. To date, there are seven International Working Group on the Diabetic Foot (IWGDF) guidelines published to assist healthcare providers in managing diabetes-related foot disease around the world.

Dynamic exposure and body burden models for per- and polyfluoroalkyl substances (PFAS) enable management of food safety risks in cattle.

With increasing global focus on planetary boundaries, food safety and quality, the presence of per- and polyfluoroalkyl substances (PFAS) in the food chain presents a challenge for the sustainable production and supply of quality assured food. Consumption of food is the primary PFAS exposure route for the general population. At contaminated sites, PFAS have been reported in a range of agricultural commodities including cattle.

Pregnancy Complications Are Associated with Premature Coronary Artery Disease: Linking Three Cohorts.

There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case-control study design.

Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity.

Objectives: B cells drive the production of autoreactive antibody-secreting cells (ASCs) in autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Sjögren's syndrome, causing long-term organ damage. Current treatments for antibody-mediated autoimmune diseases target B cells or broadly suppress the immune system. However, pre-existing long-lived ASCs are often refractory to treatment, leaving a reservoir of autoreactive cells that continue to produce antibodies.

Risk Factors for Early-Onset Versus Late-Onset Coronary Heart Disease (CHD): Systematic Review and Meta-Analysis.

Aim: We aimed to systematically compare literature on prevalence of modifiable and non-modifiable risk factors for early compared to late-onset coronary heart disease (CHD).

Methods: PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol registered in PROSPERO CRD42020173216). Study quality was assessed using the National Heart, Lung and Blood Institute tool for observational and case-control studies.

Sex-specific and ethnicity-specific differences in MINOCA.

Suspected myocardial infarction with non-obstructive coronary arteries (MINOCA) has received increasing attention over the past decade. Given the heterogeneity in the mechanisms underlying acute myocardial infarction in the absence of obstructive coronary arteries, the syndrome of MINOCA is considered a working diagnosis that requires further investigation after diagnostic angiography studies have been performed, including coronary magnetic resonance angiography and functional angiography. Although once considered an infrequent and low-risk form of myocardial infarction, recent data have shown that the prognosis of MINOCA is not as benign as previously assumed.

Lyophilized Lipid Liquid Crystalline Nanoparticles as an Antimicrobial Delivery System.

Lipid liquid crystalline nanoparticles (LCNPs) are unique nanocarriers that efficiently deliver antimicrobials through biological barriers. Yet, their wide application as an antimicrobial delivery system is hindered by their poor stability in aqueous dispersions. The production of dried LCNP powder via lyophilization is a promising approach to promote the stability of LCNPs.

Efficacy of Plasma-Treated Water against Salmonella Typhimurium: Antibacterial Activity, Inhibition of Invasion, and Biofilm Disruption.

Plasma-treated water (PTW) has emerged as a potential sanitizing agent. This study evaluated antibacterial activity, inhibition of invasion, and biofilm disruption effects of PTW against Typhimurium. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined for different PTW types.