Initial Implementation of the My Heart, My Life Program by the National Heart Foundation of Australia: Pilot Mixed Methods Evaluation Study.

Background: Coronary heart disease (CHD) remains the leading cause of death in Australia, with a high residual risk of repeat events in survivors. Secondary prevention therapy is crucial for reducing the risk of both death and other major adverse cardiac events. The National Heart Foundation of Australia has developed a consumer-facing support program called My Heart, My Life (MHML) to address the gap in the secondary prevention of CHD in Australia.

Telehealth is here to stay but not without challenges: a consultation of cardiac rehabilitation clinicians during COVID-19 in Victoria, Australia.

Aims: Delivery of cardiac rehabilitation (CR) was challenged during the pandemic caused by the Coronavirus disease (COVID-19), due to government stay-at-home directives which restricted in-person programmes. The Australian state of Victoria experienced the longest and most severe COVID-19 restrictions and was in lockdown for ∼6 months of 2020. We aimed to explore (i) clinicians' experiences and perceptions and (ii) identify barriers and enablers, for delivering CR during the COVID-19 pandemic.

Fractionated Dosing Improves Preclinical Therapeutic Index of Pyrrolobenzodiazepine-Containing Antibody Drug Conjugates.

To use preclinical models to identify a dosing schedule that improves tolerability of highly potent pyrrolobenzodiazepine dimers (PBDs) antibody drug conjugates (ADCs) without compromising antitumor activity. A series of dose-fractionation studies were conducted to investigate the pharmacokinetic drivers of safety and efficacy of PBD ADCs in animal models. The exposure-activity relationship was investigated in mouse xenograft models of human prostate cancer, breast cancer, and gastric cancer by comparing antitumor activity after single and fractionated dosing with tumor-targeting ADCs conjugated to SG3249, a potent PBD dimer.

Thymic stromal lymphopoietin and interleukin-4 mediate the pathogenesis of halothane-induced liver injury in mice.

Unlabelled: Liver eosinophilia has been associated with incidences of drug-induced liver injury (DILI) for more than 50 years, although its role in this disease has remained largely unknown. In this regard, it was recently shown that eosinophils played a pathogenic role in a mouse model of halothane-induced liver injury (HILI). However, the signaling events that drove hepatic expression of eosinophil-associated chemokines, eotaxins, eosinophil infiltration, and subsequent HILI were unclear.

Endogenous interleukin-4 regulates glutathione synthesis following acetaminophen-induced liver injury in mice.

In a recent study, we reported that interleukin (IL)-4 had a protective role against acetaminophen (APAP)-induced liver injury (AILI), although the mechanism of protection was unclear. Here, we carried out more detailed investigations and have shown that one way IL-4 may control the severity of AILI is by regulating glutathione (GSH) synthesis. In the present studies, the protective role of IL-4 in AILI was established definitively by showing that C57BL/6J mice made deficient in IL-4 genetically (IL-4(-/-)) or by depletion with an antibody, were more susceptible to AILI than mice not depleted of IL-4.

Pathologic role of stressed-induced glucocorticoids in drug-induced liver injury in mice.

Unlabelled: We previously reported that acetaminophen (APAP)-induced liver injury (AILI) in mice is associated with a rise in serum levels of the glucocorticoid (GC), corticosterone. In the current study, we provide evidence that endogenous GC play a pathologic role in AILI. Specifically, pretreatment of mice with the GC receptor (GCR) inhibitor, RU486 (mifepristrone), protected normal but not adrenalectomized mice from AILI, while pretreatment with dexamethasone, a synthetic GC, exacerbated AILI.

Disruption of the endoplasmic reticulum by cytotoxins in LLC-PK1 cells.

Prior induction of an endoplasmic reticulum stress response results in protection against reactive cytotoxins in the LLC-PK1 cell line. The purpose of this investigation was to determine therefore if the endoplasmic reticulum was disrupted by iodoacetamide, tert-butylhydroperoxide or sulfamethoxazole hydroxylamine. Toxic concentrations of the three toxins caused a dramatic loss of GRP94 protein within 3-8h of exposure, while induction of GRP78 and calreticulin occurred at 8 and 24h following exposure.