Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynecological malignancy. High-grade serous OC (HGSOC) is the most common and aggressive OC subtype, characterized by widespread genome changes and chromosomal instability and is consequently poorly responsive to chemotherapy treatment. The objective of this study was to investigate the role of the microRNA miR-433 in the cellular response of OC cells to paclitaxel treatment. We show that stable miR-433 expression in A2780 OC cells results in the induction of cellular senescence demonstrated by morphological changes, downregulation of phosphorylated retinoblastoma (p-Rb), and an increase in β-galactosidase activity. Furthermore, in silico analysis identified four possible miR-433 target genes associated with cellular senescence: cyclin-dependent kinase 6 (CDK6), MAPK14, E2F3, and CDKN2A. Mechanistically, we demonstrate that downregulation of p-Rb is attributable to a miR-433-dependent downregulation of CDK6, establishing it as a novel miR-433 associated gene. Interestingly, we show that high miR-433 expressing cells release miR-433 into the growth media via exosomes which in turn can induce a senescence bystander effect. Furthermore, in relation to a chemotherapeutic response, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that only PEO1 and PEO4 OC cells with the highest miR-433 expression survive paclitaxel treatment. Our data highlight how the aberrant expression of miR-433 can adversely affect intracellular signaling to mediate chemoresistance in OC cells by driving cellular senescence.

Aim: To investigate the perceptions of radiographers in the Greater Sydney metropolitan area concerning the performance of intravenous contrast media injections by radiographers. Methods: 90 radiographers (corresponds to a 40.9% return) from five randomly selected private radiology practices and five randomly selected public hospitals within the Greater Sydney metropolitan area were surveyed. The survey was structured such that each section of the survey related to a specific objective of the study. This study focuses on training, departmental workflow and medico‐legal issues. Results: Radiographers from private practices were more in favour of performing intravenous contrast media administration, although the majority of the radiographers surveyed felt that it should be performed as part of their normal duties. They felt that it would greatly aid department workflow and patient throughput. However, there were concerns about the medico‐legal implications of this added responsibility. Conclusions: Most respondents were in favour of radiographers performing contrast media injections. Standardised and accredited training, including education on the medico‐legal coverage available to them, may be needed to allay their concerns and adequately prepare them to take on this extended role.

objectives Melioidosis, caused by Burkholderia pseudomallei, is prevalent in rural areas of Malaysia. The aim of this study is to delineate the epidemiology and predictors of mortality from melioidosis in Kapit district, Sarawak.methods For this retrospective study of patients with culture-confirmed melioidosis admitted to Kapit Hospital, Sarawak, Malaysia, between July 2016 and July 2019, epidemiological, clinical and microbiological data were obtained. Univariate and multivariate logistic regression analyses were used to determine predictors of mortality.results Seventy three patients met inclusion criteria. Diabetes mellitus (28.8%) and hypertension (27.4%) were primary co-morbidities. Clinical spectrum of melioidosis ranged from bacteraemia (64.4%), pneumonia (61.6%) and internal organ abscesses (49.3%) to localised soft tissue (21.9%) and joint abscesses (6.9%). Mortality rate was 12.3%. Bacteraemia and pneumonia were significantly associated with septic shock, whereas patients with soft tissue abscesses tended to present with a milder form of melioidosis without septic shock. Septic shock, mechanical ventilation, intensive care unit admission, serum urea, creatinine, bicarbonate, albumin and aspartate transaminase were all significantly associated with increased mortality on univariate analysis (all P < 0.05). Multivariate analysis revealed that low serum bicarbonate (P = 0.004, OR 0.64, 95% CI 0.48-0.87) and albumin (P = 0.031, OR 0.73, 95% CI 0.54-0.97) could be associated with a higher mortality.conclusion Melioidosis remains a fatal infection and commonly presents with septic shock, in the form of bacteraemia and pneumonia. Two routine clinical parameters, serum bicarbonate and serum albumin, may have important prognostic implications in septicaemic melioidosis.

Background: Melioidosis, caused by Burkholderia pseudomallei, is prevalent in rural areas of Malaysia. This soil-dwelling pathogen is inherently resistant to many first-line antibiotics and carries a high mortality rate. Hence, it poses a significant burden of disease in terms of productivity losses among farmers and blue-collar workers in resource-poor environments. There are limited reports on the factors associated with mortality from melioidosis in Borneo.Methods and materials: This study delineates the epidemiological, clinical and microbiological characteristics of melioidosis, and the predictors of mortality. Seventy-three adults, with cultureconfirmed melioidosis at Kapit Hospital, Sarawak, Malaysia, over a 3-year period were retrospectively identified.Results: Among 73 patients, diabetes mellitus (28.8%; n = 21) and hypertension (27.4%; n = 20) were reported as the primary risk factors. The clinical spectrum of melioidosis may vary from localised soft tissue (21.9%; n = 16) and joint abscesses (6.9%; n = 5), to a fulminant end of the spectrum, in the form of bacteraemia (64.4%; n = 47), pneumonia (61.6%; n = 45) and internal organ abscesses (49.3%; n = 36). The mortality rate was 12.3% (n = 9). The mean time from presentation to initiation of anti-melioidosis treatment was 2.6 ± 2.3 days. Positive cultures largely came from blood (58.9%, n = 43) and sputum (28.8%; n = 21). All isolates were sensitive to Ceftazidime and 92.7% were sensitive to Gentamicin, which is a unique occurrence in Sarawak. Using univariate analyses, we identified septic shock (p < 0.001), intensive care unit admission (p = 0.001), mechanical ventilation (p < 0.001), serum urea (p < 0.001), serum creatinine (p < 0.001), serum aspartate transaminase (p = 0.037), serum bicarbonate (p < 0.001) and serum albumin (p = 0.025), to be associated with increased risk of mortality. Multivariate logistic regression analyses identified serum bicarbonate (p = 0.004, OR 0.64, 95% CI 0.48-0.87) and serum albumin (p = 0.031, OR 0.73, 95% CI 0.54-0.97), to be the independent predictors of mortality from melioidosis. Conclusion:The identification of these two routine clinical parameters, namely serum bicarbonate and serum albumin, have important prognostic implications in septicaemic melioidosis, which could potentially allow prompt recognition of critically ill patients and timely initiation of anti-melioidosis treatment.