In vivo evaluation of selenium-tellurium based nanoparticles as a novel treatment for bovine mastitis.

Background: Bovine mastitis is one of the main causes of reduced production in dairy cows. The infection of the mammary gland is mainly caused by the bacterium Staphylococcus aureus, whose resistant strains make the treatment of mastitis with conventional antibiotics very difficult and result in high losses. Therefore, it is important to develop novel therapeutic agents to overcome the resistance of mastitis-causing strains.

A model of care for Aboriginal and Torres Strait Islander prisoner health and wellbeing in South Australia.

Purpose: Aboriginal and Torres Strait Islander (Aboriginal) people are overrepresented in Australian prisons, where they experience complex health needs. A model of care was designed to respond to the broad needs of the Aboriginal prisoner population within the nine adult prisons across South Australia. The purpose of this paper is to describe the methods and findings of the Model of Care for Aboriginal and Torres Strait Islander Prisoner Health and Wellbeing for South Australia.

Neutrophils in Cancer immunotherapy: friends or foes?

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis.

Priority setting: Development of the South Australian Aboriginal Chronic Disease Consortium RoadMap for Action.

Issues Addressed: Aboriginal and Torres Strait Islander (Aboriginal) people in South Australia are overburdened by cardiovascular disease, diabetes and cancer. The South Australian Aboriginal Chronic Disease Consortium (Consortium) was established in June 2017 as a collaborative partnership to lead the implementation of three state-wide chronic disease plans using a strategic approach to identifying key priority areas for action.

Methods: In 2017-2018, the Consortium Coordinating Centre facilitated a priority setting process, which involved extensive consultation, including a prioritisation survey and stakeholder workshops.

Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells.

Background & Aims: Metallothionein-3 (hMT3) is a structurally unique member of the metallothioneins family of low-mass cysteine-rich proteins. hMT3 has poorly characterized functions, and its importance for hepatocellular carcinoma (HCC) cells has not yet been elucidated. Therefore, we investigated the molecular mechanisms driven by hMT3 with a special emphasis on susceptibility to sorafenib.

Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules.

Ferritins are globular proteins with an internal cavity that enables the encapsulation of a plethora of low-mass compounds. Unfortunately, the overall negative surface charge of ferritin's internal cavity hampers efficient loading of negatively charged molecules. Therefore, we produced a genetically engineered human H-chain ferritin containing a cationic RKRK domain, reversing the natural net charge of the cavity to positive, thus allowing for efficient encapsulation of negatively charged siRNA.

Proteinase-activated Receptor 2: Springboard of Tumors.

Proteinase-activated receptors (PARs) were discovered more than 25 years ago and since then, their role in cancer has been under investigation. Research has primarily focused on the receptors located on the membrane of cancer cells and their impact on metabolism, intracellular signalling, and proliferation. Regarding the host response to cancer, studies have predominantly examined the relationship of thrombin receptors (PAR-1, PAR-3, and PAR-4) with blood clotting in distant metastatic spread.

BODIPY-labelled acetylcholinesterase reactivators can be encapsulated into ferritin nanovehicles for enhanced bioavailability in the CNS.

The BODIPY-labelled oxime reactivator was prepared and used to study its biodistribution into central nervous system. The newly synthesized oxime was found to be weak inhibitor of acetylcholinesterase and strong inhibitor of butyrylcholinesterase. Its reactivation ability for organophosphate inhibited acetylcholinesterase was found similar to a parent oxime.

Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).

Phosphoinositide 3-kinases (PI3K) and phosphoinositide 3-kinase-related protein kinases (PIKK) are two structurally related families of kinases that play vital roles in cell growth and DNA damage repair. Dysfunction of PIKK members and aberrant stimulation of the PI3K/AKT/mTOR signalling pathway are linked to a plethora of diseases including cancer. In recent decades, numerous inhibitors related to the PI3K/AKT/mTOR signalling have made great strides in cancer treatment, like copanlisib and sirolimus.

PATTERN OF MMP2 AND MMP9 EXPRESSION DEPENDS ON BREAST CANCER PATIENTS' AGE.

Background: Despite the large number of studies devoted to the study of the features of tumor microenvironment in breast cancer (BCa), presently there is no consensus on the features of MMP-2 and MMP-9 expression in the tumor tissue of BCa patients depending on the age. The aim of the study was to investigate the relationship between MMP-2 and -9 expression at the protein and mRNA levels in BCa tissues and the clinical and pathological features of BCapatientsin different age groups.

Materials And Methods: The expression level of MMP-2 and -9in the BCa tissue of patients of two age groups (< 45 years and > 45 years) was studied using the bioinformatics method (UALCAN database), immunohistochemical method, and real-time PCR.

An Aboriginal-led consortium approach to chronic disease action for health equity and holistic wellbeing.

Issue Addressed: The Wellbeing Economy, which places human and ecological wellbeing at the centre of policy making, aligns with holistic Aboriginal and Torres Strait Islander conceptualisations of health and wellbeing. In order to address chronic diseases in South Australian Aboriginal and Torres Strait Islander populations, the South Australian Aboriginal Chronic Disease Consortium (Consortium) is fostering action in ways that align both with the Wellbeing Economy and with Health in All Policies (HiAP) approaches.

Methods: In June 2017, the Consortium was established as a collaborative partnership between government and non-government organisations, researchers, Aboriginal organisations and communities to lead the effective implementation of three state-wide chronic disease plans.

Duration of forensic psychiatric care and subsequent criminal recidivism in individuals sentenced in Sweden between 2009 and 2019.

Background: The duration of forensic psychiatric care is in Sweden not determined at the time of sentencing; instead, offenders are regularly evaluated, often with regard to risk of criminal recidivism. The length and justifiability of such a sanction have been greatly debated; however, previous estimates of treatment duration based on datasets delimited to discharged patients-have provided an uncertain groundwork for these deliberations. The aim of this study was to use a more suitable approach to calculate average duration of forensic psychiatric care and to examine the relationship between length of treatment and subsequent recidivism after discharge.

PROGNOSTIC ROLE OF RESIDUAL TUMOR FEATURES IN HER2-NEGATIVE BREAST CANCER.

Unlabelled: The aim of the study was to examine the prognostic value of immunobiological markers (tumor-infiltrating lymphocytes (TILs) and their subpopulations) in residual tumor after neoadjuvant chemotherapy (NACT) completion in patients with triple negative (TNBC) and luminal B HER2-neu negative breast cancer (LBBC).

Materials And Methods: The analysis of the treatment results of 59 patients with TNBC and 56 patients with LBBC with stage IIB-IIIB who received NACT was performed. The levels of TILs and their subpopulations (FOXP3+, CD4+, CD8+) in patients at the time of diagnosis in core-needle biopsy material and in residual tumor in postoperative material were studied by immunohistochemical method.

Platinum-based drug-induced depletion of amino acids in the kidneys and liver.

Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a widely used cytostatic agent; however, it tends to promote kidney and liver disease, which are a major signs of drug-induced toxicity. Platinum compounds are often presented as alternative therapeutics and subsequently easily dispersed in the environment as contaminants. Due to the major roles of the liver and kidneys in removing toxic materials from the human body, we performed a comparative study of the amino acid profiles in chicken liver and kidneys before and after the application of CDDP and platinum nanoparticles (PtNPs-10 and PtNPs-40).

HPMA Copolymer Mebendazole Conjugate Allows Systemic Administration and Possesses Antitumour Activity In Vivo.

Mebendazole and other benzimidazole antihelmintics, such as albendazole, fenbendazole, or flubendazole, have been shown to possess antitumour activity, primarily due to their microtubule-disrupting activity. However, the extremely poor water-solubility of mebendazole and other benzimidazoles, resulting in very low bioavailability, is a serious drawback of this class of drugs. Thus, the investigation of their antitumour potential has been limited so far to administering repeated high doses given peroral (p.

Simultaneous Delivery of Doxorubicin and Protease Inhibitor Derivative to Solid Tumors via Star-Shaped Polymer Nanomedicines Overcomes P-gp- and STAT3-Mediated Chemoresistance.

The derivative of protease inhibitor ritonavir (5-methyl-4-oxohexanoic acid ritonavir ester; RD) was recently recognized as a potent P-gp inhibitor and cancerostatic drug inhibiting the proteasome and STAT3 signaling. Therefore, we designed high-molecular-weight HPMA copolymer conjugates with a PAMAM dendrimer core bearing both doxorubicin (Dox) and RD (Star-RD + Dox) to increase the circulation half-life to maximize simultaneous delivery of Dox and RD into the tumor. Star-RD inhibited P-gp activity, potently sensitizing both low- and high-P-gp-expressing cancer cells to the cytostatic and proapoptotic activity of Dox in vitro.

IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25Foxp3 T cells.

Complexes of IL-2 and JES6-1 mAb (IL-2/JES6) provide strong sustained IL-2 signal selective for CD25 cells and thus they potently expand T cells. IL-2/JES6 are effective in the treatment of autoimmune diseases and in protecting against rejection of pancreatic islet allografts. However, we found that IL-2/JES6 also dramatically increase sensitivity to LPS-mediated shock in C57BL/6 mice.

Improving the well-being for young people living with rheumatic heart disease: A peer support pilot program through Danila Dilba Health Service.

Issue Addressed: Aboriginal and Torres Strait Islander peoples in Australia have an inequitable burden of acute rheumatic fever (ARF) and rheumatic heart disease (RHD), concentrated among young people and necessitating ongoing medical care during adolescence. There is an unmet need for improved well-being and support for these young people to complement current biomedical management.

Methods: This pilot program initiative aimed to determine the suitability and appropriate format of an ongoing peer support program to address the needs of young people living with RHD in urban Darwin.

Polymer-ritonavir derivate nanomedicine with pH-sensitive activation possesses potent anti-tumor activity in vivo via inhibition of proteasome and STAT3 signaling.

Drug repurposing is a promising strategy for identifying new applications for approved drugs. Here, we describe a polymer biomaterial composed of the antiretroviral drug ritonavir derivative (5-methyl-4-oxohexanoic acid ritonavir ester; RD), covalently bound to HPMA copolymer carrier via a pH-sensitive hydrazone bond (P-RD). Apart from being more potent inhibitor of P-glycoprotein in comparison to ritonavir, we found RD to have considerable cytostatic activity in six mice (IC ~ 2.

Gene silencing delivery systems for the treatment of pancreatic cancer: Where and what to target next?

Despite intensive research efforts and development of numerous new anticancer drugs and treatment strategies over the past decades, there has been only very limited improvement in overall patient survival and in effective treatment options for pancreatic cancer. Current chemotherapy improves survival in terms of months and death rates in pancreatic cancer patients are almost equivalent to incidence rates. It is imperative to develop new therapeutic approaches.

"Language Breathes Life"-Barngarla Community Perspectives on the Wellbeing Impacts of Reclaiming a Dormant Australian Aboriginal Language.

Traditional languages are a key element of Indigenous peoples' identity, cultural expression, autonomy, spiritual and intellectual sovereignty, and wellbeing. While the links between Indigenous language loss and poor mental health have been demonstrated in several settings, little research has sought to identify the potential psychological benefits that may derive from language reclamation. The revival of the Barngarla language on the Eyre Peninsula, South Australia, offers a unique opportunity to examine whether improvements in mental health and social and emotional wellbeing can occur during and following the language reclamation process.

Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue.

The delivery of nitric oxide (NO) specifically to solid tumours was explored in this study as a strategy to augment the passive accumulation of nanomedicines in tumours induced by the Enhanced Permeability and Retention (EPR) effect. An increase in accumulation was achieved by the binding of the chemical precursor of NO, based on an organic nitrate, to a water-soluble synthetic polymer drug carrier. Four structurally different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer NO donors were synthesized.

Towards the development of a wellbeing model for aboriginal and Torres Strait islander peoples living with chronic disease.

Background: Re-defining the way in which care is delivered, to reflect Aboriginal and Torres Strait Islander peoples' needs and values, is essential for improving the accessibility of primary healthcare. This study focused on developing a Framework to support the quality of care and quality of life of, as well as treatment for, Aboriginal and Torres Strait Islander peoples living with chronic disease.

Methods: A team of researchers, including thirteen experienced Aboriginal healthcare professionals, came together to undertake this important work.