Reduced PI3K(p110α) induces atrial myopathy, and PI3K-related lipids are dysregulated in athletes with atrial fibrillation.

Background: Elucidating mechanisms underlying atrial myopathy, which predisposes individuals to atrial fibrillation (AF), will be critical for preventing/treating AF. In a serendipitous discovery, we identified atrial enlargement, fibrosis, and thrombi in mice with reduced phosphoinositide 3-kinase (PI3K) in cardiomyocytes. PI3K(p110α) is elevated in the heart with exercise and is critical for exercise-induced ventricular enlargement and protection, but the role in the atria was unknown.

Phage Therapy in Korea: A Prescribers' Survey of Attitudes Amongst Korean Infectious Diseases Specialists Towards Phage Therapy.

Background: Concerns about the rise in antimicrobial resistance have led to renewed interest in phage therapy worldwide, but perceptions among relevant medical professionals in Korea remain largely unknown.

Materials And Methods: We conducted a semi-quantitative online survey to evaluate the Korean infectious disease specialists' perception of phage therapy.

Results: We sent out the link to the questionnaire to 380 subjects and received 91 replies, with 90/91 respondents identifying as Korean infectious diseases specialists or trainees.

Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial.

Introduction: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.

Methods And Analysis: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia's Therapeutic Goods Administration Special Access Scheme.

Novel gene-intergenic fusion involving ubiquitin E3 ligase UBE3C causes distal hereditary motor neuropathy.

Distal hereditary motor neuropathies (dHMNs) are a group of inherited diseases involving the progressive, length-dependent axonal degeneration of the lower motor neurons. There are currently 29 reported causative genes and four disease loci implicated in dHMN. Despite the high genetic heterogeneity, mutations in the known genes account for less than 20% of dHMN cases, with the mutations identified predominantly being point mutations or indels.

Data to Power Precision Phage Therapy: A Look at the Phage Directory-Phage Australia Partnership.

Phage Directory has recently partnered with Phage Australia to help optimize Australia's data-centric standardized approach to personalized phage therapy. Here is a behind-the-scenes look at the genesis of Phage Australia, how the Phage Directory-Phage Australia partnership started, and what it is working toward.

3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies.

Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics conditions and pathological conditions such as cancer. In comparison to biospecimens taken from tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma - an aggressive cancer with very limited effective treatment options.

Two plus One: Combination Therapy Tri-systems Involving Two Membrane-Disrupting Antimicrobial Macromolecules and Antibiotics.

The escalating issue of multidrug-resistant (MDR) bacteria indicates the urgent need for new and effective strategies to combat this global health challenge. Here, we describe a new combinatorial approach that can be put forward for experimental therapy application against MDR bacteria. Specifically, we have developed a tri-system that includes the coadministration of two different membrane-disrupting-type antimicrobial agents─a synthetic antimicrobial polymer and an antimicrobial peptide (AMP) colistin methanesulfonate ()─in conjunction with an antibiotic [doxycycline (), rifampicin (), or azithromycin ()].

Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child.

Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7-year-old child. Monitoring of phage and bacterial kinetics allowed real-time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment.

Transcriptome analysis of islets from diabetes-resistant and diabetes-prone obese mice reveals novel gene regulatory networks involved in beta-cell compensation and failure.

The mechanisms underpinning beta-cell compensation for obesity-associated insulin resistance and beta-cell failure in type 2 diabetes remain poorly understood. We used a large-scale strategy to determine the time-dependent transcriptomic changes in islets of diabetes-prone db/db and diabetes-resistant ob/ob mice at 6 and 16 weeks of age. Differentially expressed genes were subjected to cluster, gene ontology, pathway and gene set enrichment analyses.

A Phage Therapy Guide for Clinicians and Basic Scientists: Background and Highlighting Applications for Developing Countries.

Approximately 10% of global health research is devoted to 90% of global disease burden (the so-called "10/90 Gap") and it often neglects those diseases most prevalent in low-income countries. Antibiotic resistant bacterial infections are known to impact on healthcare, food security, and socio-economic fabric in the developing countries. With a global antibiotic resistance crisis currently reaching a critical level, the unmet needs in the developing countries are even more striking.

Skeletal glucocorticoid signalling determines leptin resistance and obesity in aging mice.

Objective: Aging and chronic glucocorticoid excess share a number of critical features, including the development of central obesity, insulin resistance and osteoporosis. Previous studies have shown that skeletal glucocorticoid signalling increases with aging and that osteoblasts mediate the detrimental skeletal and metabolic effects of chronic glucocorticoid excess. Here, we investigated whether endogenous glucocorticoid action in the skeleton contributes to metabolic dysfunction during normal aging.

Vascular transcriptome landscape of Trail mice: Implications and therapeutic strategies for diabetic vascular disease.

Circulating plasma TRAIL levels are suppressed in patients with cardiovascular and diabetic diseases. To identify novel targets in vascular metabolic diseases, genome-wide transcriptome of aortic tissue from Trail versus Trail mice were interrogated. We found 861 genes differentially expressed with TRAIL deletion.

Publisher Correction: Safety of bacteriophage therapy in severe Staphylococcus aureus infection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Safety of bacteriophage therapy in severe Staphylococcus aureus infection.

In this single-arm non-comparative trial, 13 patients in an Australian hospital with severe Staphylococcus aureus infections were intravenously administered a good manufacturing practice-quality preparation of three Myoviridae bacteriophages (AB-SA01) as adjunctive therapy. AB-SA01 was intravenously administered twice daily for 14 d and the clinical, haematological and blood biochemical parameters of the recipients were monitored for 90 d. The primary outcome was the assessment of safety and tolerability (that is, pain and redness at the infusion site and systemic adverse reactions, such as fever, tachycardia, hypotension, diarrhoea or abdominal pain and the development of renal or hepatic dysfunction).

Characterizing the role of porin mutations in susceptibility of beta lactamase producing Klebsiella pneumoniae isolates to ceftaroline and ceftaroline-avibactam.

Objectives: Evaluate the role of porins in the susceptibility of Klebsiella pneumoniae to ceftaroline and ceftaroline-avibactam.

Methods: Susceptibility to ceftaroline and ceftaroline-avibactam was tested by broth microdilution method in Klebsiella pneumoniae isolates (n = 65), including isogenic mutants (n = 30) and clinical isolates (n = 35), with different outer membrane porin defects in the presence or absence of beta lactamases.

Results: Ceftaroline exhibited excellent activity against all the isogenic porin mutants with a MIC range of 0.

Replicable Expansion and Differentiation of Neural Precursors from Adult Canine Skin.

Repopulation of brain circuits by neural precursors is a potential therapeutic strategy for neurodegenerative disorders; however, choice of cell is critical. Previously, we introduced a two-step culture system that generates a high yield of neural precursors from small samples of adult canine skin. Here, we probe their gene and protein expression profiles in comparison with dermal fibroblasts and brain-derived neural stem cells and characterize their neuronal potential.

MicroRNA gene expression signatures in long-surviving malignant pleural mesothelioma patients.

Malignant pleural mesothelioma (MPM) is a tumor originating in the mesothelium, the membrane lining the thoracic cavities, and is induced by exposure to asbestos. Australia suffers one of the world's highest rates of MPM and the incidence is yet to peak. The prognosis for patients with MPM is poor and median survival following diagnosis is 4-18 months.

Sex differences in response to miRNA-34a therapy in mouse models of cardiac disease: identification of sex-, disease- and treatment-regulated miRNAs.

Key Points: MicroRNA (miRNA)-based therapies are in development for numerous diseases, including heart disease. Currently, very limited basic information is available on the regulation of specific miRNAs in male and female hearts in settings of disease. The identification of sex-specific miRNA signatures has implications for translation into the clinic and suggests the need for customised therapy.

KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets.

Identification of miR-34 regulatory networks in settings of disease and antimiR-therapy: Implications for treating cardiac pathology and other diseases.

Expression of the miR-34 family (miR-34a, -34b, -34c) is elevated in settings of heart disease, and inhibition with antimiR-34a/antimiR-34 has emerged as a promising therapeutic strategy. Under chronic cardiac disease settings, targeting the entire miR-34 family is more effective than targeting miR-34a alone. The identification of transcription factor (TF)-miRNA regulatory networks has added complexity to understanding the therapeutic potential of miRNA-based therapies.