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The aim of this study was to explore the experiences of frontline nurses caring for patients during the first 6 months of the COVID-19 pandemic. The JBI manual for evidence synthesis and the PRISMA guidelines for reporting. CINAHL Complete, MEDLINE, PsycINFO (EBSCO) and Scopus (Elsevier). The JBI Mixed Methods Data Extraction Tool following a Convergent Integrated Approach. Nineteen studies were included in the review, comprising eight countries and 2525 frontline nurses. Six themes emerged encompassing frontline nurses' COVID-19 experiences including emotional experiences, physical symptoms, ethical and moral challenges, professional impact, risk factors for negative emotional experiences and protective factors for future pandemic events. Frontline nurses have faced numerous challenges during the COVID-19 pandemic. Providing frontline nurses with the required resources and support to perform their roles in global healthcare crises allows for an empowered and resilient workforce ensuring nurses remain in their chosen profession.

The World Health Organization estimates that approximately 180,000 health care workers have died in the fight against COVID-19. Emergency nurses have experienced relentless pressure in maintaining the health and well-being of their patients, often to their detriment. This research aimed to gain an understanding of lived experiences of Australian emergency nurses working on the frontline during the first year of the COVID-19 pandemic. A qualitative research design was used, guided by an interpretive hermeneutic phenomenological approach. A total of 10 Victorian emergency nurses from both regional and metropolitan hospitals were interviewed between September and November 2020. Analysis was undertaken using a thematic analysis method. A total of 4 major themes were produced from the data. The 4 overarching themes included mixed messages, changes to practice, living through a pandemic, and 2021: here we come. Emergency nurses have been exposed to extreme physical, mental, and emotional conditions as a result of the COVID-19 pandemic. A greater emphasis on the mental and emotional well-being of frontline workers is paramount to the success of maintaining a strong and resilient health care workforce.

The need for continued research into suicide prevention strategies is undeniable, with high global statistics demonstrating the urgency of this public health issue. In Australia, approximately 3000 people end their lives each year, with those living in rural and regional areas identified as having a higher risk of dying by suicide. Due to decreased access and support services in these areas, community-based suicide prevention initiatives provide opportunities to educate and support local communities. A scoping review was conducted to explore the literature pertaining to such programs in rural and/or regional communities in Australia. This review follows the five-stage Arksey and O’Malley (2005) framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Nine databases were searched, from which studies were considered eligible if suicide prevention programs were community-based and catered for adults (aged ≥ 18 years) in rural or regional Australia. Ten papers that met our inclusion criteria were included in this review, showcasing a variety of interventions such as workshops, a digital intervention, art therapy, and initiatives to increase education and reduce stigma around suicide. Program engagement strategies included the importance of providing culturally appropriate services, the inclusion of lived experience mentoring, and tailoring the suicide prevention program to reach its targeted audience. Overall, there is a dearth of literature surrounding community-based suicide prevention initiatives for adults in rural and regional Australia. Further evaluation of community-based projects is required to ensure quality improvement and tailored suicide prevention initiatives for rural and regional Australians.

Background: To improve preventative health screening in regional Victoria, Australia, a collaborative student-led health prevention strategy was initiated. The aim of this study is to evaluate the impact of four health check clinics using a free ‘pop-up’ format within community settings.Methods: A mixed methods, explanatory sequential design was used to explore community health data and participant experiences in utilising the free health check clinics. The clinics were delivered over 6 months and located in three different communities within the regional government area. Descriptive statistics were used to analyse participant health data and a thematic analysis was utilised to determine themes from participant feedback and health outcomes.Results: The clinics were attended by 188 community members, largely impacted by government lockdowns during the coronavirus disease 2019 (COVID-19) pandemic. Health check results indicate the population is overweight and at high risk of diabetes. Participants enjoyed the free and convenient nature of the health check program and the location of the venues. Feedback from participants indicate the health education provided was useful and advocated for changes in current behaviours. Many embraced the new information and community connections and made changes to improve their future health. Others claimed to enjoy the clinic experience but reported no action from the recommendations.Conclusions: Evaluation of the health check clinics indicate they had a minor, yet positive impact on the local community in increasing engagement with preventative screening strategies. COVID-19 restrictions impacted participant numbers and thus more research is needed in a time where community movement is not limited.

Patients with ER-negative breast cancer have the worst prognosis of all breast cancer subtypes, often experiencing rapid recurrence or progression to metastatic disease shortly after diagnosis. Given that metastasis is the primary cause of mortality in most solid tumors, understanding metastatic biology is crucial for effective intervention. Using a mouse systems genetics approach, we previously identified 12 genes associated with metastatic susceptibility. Here, we extend those studies to identify Resf1 , a poorly characterized gene, as a novel metastasis susceptibility gene in ER- breast cancer. Resf1 is a large, unstructured protein with an evolutionarily conserved intron-exon structure, but with poor amino acid conservation. CRISPR or gene trap mouse models crossed to the Polyoma Middle-T antigen genetically engineered mouse model (MMTV-PyMT) demonstrated that reduction of Resf1 resulted in a significant increase in tumor growth, a shortened overall survival time, and increased incidence and number of lung metastases, consistent with patient data. Furthermore, an analysis of matched tail and primary tissues revealed loss of the wildtype copy in tumor tissue, consistent with Resf1 being a tumor suppressor. Mechanistic analysis revealed a potential role of Resf1 in transcriptional control through association with compound G4 quadruplexes in expressed sequences, particularly those associated with ribosomal biogenesis. These results suggest that loss of Resf1 enhances tumor progression in ER- breast cancer through multiple alterations in both transcriptional and translational control.

Hundreds of organic chemicals are used during natural gas extraction via high-volume hydraulic fracturing (HVHF). However, it is unclear whether these chemicals, injected into deep shale horizons, reach shallow groundwater aquifers and affect local water quality, either from those deep HVHF injection sites or from the surface or shallow subsurface. Here, we report detectable levels of organic compounds in shallow groundwater samples from private residential wells overlying the Marcellus Shale in northeastern Pennsylvania. Analyses of purgeable and extractable organic compounds from 64 groundwater samples revealed trace levels of volatile organic compounds, well below the Environmental Protection Agency’s maximum contaminant levels, and low levels of both gasoline range (0–8 ppb) and diesel range organic compounds (DRO; 0–157 ppb). A compound-specific analysis revealed the presence of bis(2-ethylhexyl) phthalate, which is a disclosed HVHF additive, that was notably absent in a representative geogenic water sample and field blanks. Pairing these analyses with (i) inorganic chemical fingerprinting of deep saline groundwater, (ii) characteristic noble gas isotopes, and (iii) spatial relationships between active shale gas extraction wells and wells with disclosed environmental health and safety violations, we differentiate between a chemical signature associated with naturally occurring saline groundwater and one associated with alternative anthropogenic routes from the surface (e.g., accidental spills or leaks). The data support a transport mechanism of DRO to groundwater via accidental release of fracturing fluid chemicals derived from the surface rather than subsurface flow of these fluids from the underlying shale formation.

Objective To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay transition to psychotic disorders for people at high risk.Design Systematic review and meta-analysis. Data sources Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status. Review methods Randomised trials comparing any psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising the results.Results 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range 51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference −0.07 (−0.14 to −0.01). Very low quality evidence for omega-3 fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions in transition to psychosis at 12 months.Conclusions Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis.

The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual. A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual. The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first. Genetic discordance of the two SARS-CoV-2 specimens was greater than could be accounted for by short-term in vivo evolution. These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application. Nevada IDEA Network of Biomedical Research, and the National Institute of General Medical Sciences (National Institutes of Health).

KDM5 histone demethylases promote the survival of drug-tolerant persister (DTP) cells in certain cancers. CPI-455, a chemical probe specific for KDM5, elevates cellular H3K4 methylation levels and reduces DTP cell numbers, suggesting that KDM5 is a viable target for cancer combination treatment. The KDM5 family of histone demethylases catalyzes the demethylation of histone H3 on lysine 4 (H3K4) and is required for the survival of drug-tolerant persister cancer cells (DTPs). Here we report the discovery and characterization of the specific KDM5 inhibitor CPI-455. The crystal structure of KDM5A revealed the mechanism of inhibition of CPI-455 as well as the topological arrangements of protein domains that influence substrate binding. CPI-455 mediated KDM5 inhibition, elevated global levels of H3K4 trimethylation (H3K4me3) and decreased the number of DTPs in multiple cancer cell line models treated with standard chemotherapy or targeted agents. These findings show that pretreatment of cancer cells with a KDM5-specific inhibitor results in the ablation of a subpopulation of cancer cells that can serve as the founders for therapeutic relapse.