With evidence that salpingectomy is effective in preventing high grade serous carcinoma, it is time to consider offering this procedure to people at higher-than-average lifetime risk for ovarian cancer, despite not having a pathogenic genetic variant that increases risk for ovarian cancer. This targeted approach has potential to be effective at reducing ovarian cancer incidence, and unlike opportunistic salpingectomy is focused on people with an increased lifetime risk of ovarian cancer. However, the acceptability of this approach within the population of potential patients remains unknown.
View Article and Find Full Text PDFUnderstanding the fundamental biochemical and metabolic requirements for the replication of coronaviruses within infected cells is of notable interest for the development of broad-based therapeutic strategies, given the likelihood of the emergence of new pandemic-potential virus species, as well as future variants of SARS-CoV-2. Here we demonstrate members of the glutaminase family of enzymes (GLS and GLS2), which catalyze the hydrolysis of glutamine to glutamate (i.e.
View Article and Find Full Text PDFBackground: The recent crises of bushfires, floods, and the COVID-19 pandemic on the southeast coast of Australia were unprecedented in their extent and intensity. Few studies have investigated responses to cumulative disasters in First Nations communities, despite acknowledgement that these crises disproportionately impact First Nations people. This study was conducted by Aboriginal and non-Aboriginal researchers in partnership with Waminda, South Coast Women's Health and Wellbeing Aboriginal Corporation, an Aboriginal Community Controlled Health Organisation (ACCHO).
View Article and Find Full Text PDFCultured cancer cells frequently rely on the consumption of glutamine and its subsequent hydrolysis by glutaminase (GLS). However, this metabolic addiction can be lost in the tumour microenvironment, rendering GLS inhibitors ineffective in the clinic. Here we show that glutamine-addicted breast cancer cells adapt to chronic glutamine starvation, or GLS inhibition, via AMPK-mediated upregulation of the serine synthesis pathway (SSP).
View Article and Find Full Text PDFBackground: Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin.
Methods: Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge.
Accelerated SuFEx Click Chemistry (ASCC) is a powerful method for coupling aryl and alkyl alcohols with SuFEx-compatible functional groups. With its hallmark favorable kinetics and exceptional product yields, ASCC streamlines the synthetic workflow, simplifies the purification process, and is ideally suited for discovering functional molecules. We showcase the versatility and practicality of the ASCC reaction as a tool for the late-stage derivatization of bioactive molecules and in the array synthesis of sulfonate-linked, high-potency, microtubule targeting agents (MTAs) that exhibit nanomolar anticancer activity against multidrug-resistant cancer cell lines.
View Article and Find Full Text PDFEpithelial ovarian cancer (EOC) is a heterogeneous group of malignancies, including high-grade serous ovarian cancer (HGSC). HGSC is often diagnosed at advanced stages and is linked to TP53 variants. While variants elevate risk, most HGSC cases occur in individuals without known genetic variants, necessitating prevention strategies for people without known high-risk genetic variants.
View Article and Find Full Text PDFUnlabelled: Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential therapeutic strategy which involves targeting members of the glutaminase family of mitochondrial metabolic enzymes (GLS and GLS2), which catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. We show three examples where GLS expression increases during coronavirus infection of host cells, and another in which GLS2 is upregulated.
View Article and Find Full Text PDFThe different cell types in the brain have highly specialized roles with unique metabolic requirements. Normal brain function requires the coordinated partitioning of metabolic pathways between these cells, such as in the neuron-astrocyte glutamate-glutamine cycle. An emerging theme in glioblastoma (GBM) biology is that malignant cells integrate into or "hijack" brain metabolism, co-opting neurons and glia for the supply of nutrients and recycling of waste products.
View Article and Find Full Text PDFUsing retrospective data from U.S. Food and Drug Administration-approved/cleared molecular vaginal panels, molecular methods were found to have higher detection for vaginitis and lower detection for bacterial vaginitis when compared to probe-based methods.
View Article and Find Full Text PDFSelf-care is essential to improving heart failure patient outcomes. However, the knowledge and behaviours necessary for self-care decision making, such as symptom perception and management, are complex and require patient education. The objective of this study was to test the feasibility, acceptability, and potential effectiveness of a web-based, gamified heart failure patient education solution, Heart Self-Care Patient Education (HeartSCaPE), that used narrative and virtual reward gamification techniques.
View Article and Find Full Text PDFBackground: There is a disproportionate representation of Aboriginal children in the Australian Out of Home Care system. An important strategy to ensure Aboriginal children experience trauma informed care that is culturally situated is to have access to Aboriginal practitioners. The experiences of Aboriginal practitioners working in Aboriginal Out of Home Care have not been explored thoroughly.
View Article and Find Full Text PDFA concise semi-synthesis of the alkaloids, (-)-jerantinine A and (-)-melodinine P, and derivatives thereof, is reported. The novel compounds were shown to have potent activity against MDA-MB-231 triple-negative breast cancer cells. Furthermore, unbiased metabolomics and live cell reporter assays reveal (-)-jerantinine A alters cellular redox metabolism and induces oxidative stress that coincides with cell cycle arrest.
View Article and Find Full Text PDF(C. coli) is a gram negative, non-spore forming, mobile, curved, or spiral-shaped rod organisms and one of the most common gastrointestinal human pathogens. Campylobacter very rarely causes bacteremia.
View Article and Find Full Text PDFHeart failure is a complex, chronic disease that requires self-care to manage, and patients need support and education to perform adequate self-care. Although electronic health interventions to support behavior change and self-care in cardiovascular disease are gaining traction, there is little engaging online education specifically designed for heart failure patients. This paper describes the design and development of a heart failure self-care patient education Web site that integrated gamification, meaning the use of game design elements in a non-game context.
View Article and Find Full Text PDFBackground: More research is needed that compares the outcomes between those who underwent a hysterectomy for endometriosis with conservation of one or both ovaries and those who underwent a hysterectomy with bilateral salpingo-oophorectomy.
Objective: This study aimed to compare the rate and types of reoperations (primary outcome) and use of other pain-related health services (secondary outcomes) among people who underwent a hysterectomy with conservation of both ovaries, those who underwent a hysterectomy with unilateral salpingo-oophorectomy, and those who underwent a hysterectomy with bilateral salpingo-oophorectomy.
Study Design: This was a population-based, retrospective cohort study of 4489 patients aged 19 to 50 years in British Columbia, Canada, who underwent a hysterectomy for endometriosis between 2001 and 2016.
The Cepheid Xpert® Xpress SARS-CoV-2 assay is 1 of the several real-time reverse transcription polymerase chain reaction (RT-PCR) assays that received Emergency Use Authorization from the United States Food and Drug Administration (FDA) for detection of SARS-CoV-2. Here we report 4 SARS-CoV-2 samples that were reported as presumptive positives on the Cepheid platform while reported as positives on alternative RT-PCR platforms. Whole genome sequencing indicated that the samples were Delta variants and had point mutations in the N gene which potentially interfered with SARS-CoV-2 detection.
View Article and Find Full Text PDFAn elevated neutrophil-lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells.
View Article and Find Full Text PDFIntroduction: Team-based care can improve integrated health services by increasing comprehensiveness and continuity of care in primary healthcare (PHC) settings. Collaborative models involving providers from different professions can help to achieve coordinated, high-quality person-centred care. In Canada, there has been variation in both the timing/pace of adoption and approach to interprofessional PHC (IPHC) policy.
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