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Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms. Indeed, STAT1 signaling downregulates NQO1, a key ROS scavenger, in many breast cancer models. Moreover, genetic ablation or pharmacological inhibition of NQO1 using β-lapachone (an NQO1 bioactivatable drug) increases oxidative stress to selectively sensitize breast cancer models, including patient derived xenografts of HER2+ and triple negative disease, to the tumoricidal effects of phenformin. We provide evidence that therapies targeting ROS scavengers increase the anti-neoplastic efficacy of mitochondrial complex I inhibitors in breast cancer., Complex I inhibition induces oxidative stress leading to cancer cell cytotoxicity. Here, the authors show, in breast cancer models, that inflammatory mediators can potentiate complex I inhibitor phenformin cytotoxicity through STAT1-mediated downregulation of the reactive oxygen species scavenger NQO1.

COVID-19 had a huge impact on healthcare systems globally. Institutions, care teams and individuals made considerable efforts to adapt their practices. The present longitudinal, mixed-methods study examined a large sample of healthcare institution employees in Switzerland. Organisational resilience processes were assessed by identifying problematic real-world situations and evaluating how they were managed during three phases of the pandemic's first year. Results highlighted differences between resilience processes across the different types of problematic situations encountered by healthcare workers. Four configurations of organisational resilience were identified depending on teams' performance and ability to adapt over time: "learning from mistakes", "effective development", "new standards" and "hindered resilience". Resilience trajectories differed depending on professional categories, hierarchical status and the problematic situation's perceived severity. Factors promoting or impairing organisational resilience are discussed. Findings highlighted the importance of individuals', teams' and institutions'

Background Intensive care workers are known for their stressful work environment and for a high prevalence of mental health outcomes. The aim of this study was to evaluate the mental health, well-being and changes in lifestyle among intensive care unit (ICU) healthcare workers (HCW) during the first wave of the COVID-19 pandemic and to compare these results with those of HCW in other hospital units. Another objective was to understand which associated factors aggravate their mental health during the COVID-19 outbreak. Methods This cross-sectional survey collected socio-demographic data, lifestyle changes and mental health evaluations as assessed by the Generalized Anxiety Disorder 7 items (GAD-7), the Patient Health Questionnaire 9 items (PHQ-9), the Peritraumatic Distress Inventory (PDI) and the World Health Organization Well-Being Index (WHO-5) from the 28th May to 7th July 2020. The study was carried out at Geneva University Hospitals, a group of eight public hospitals in Switzerland. ICU HCW were analyzed for mental health outcomes and lifestyles changes and then compared to non-ICU HCW. A series of linear regression analyses were performed to assess factors associated with mental health scores. Results A total of 3461 HCW were included in the study, with 352 ICU HCW. Among ICU HCW, 145 (41%) showed low well-being, 162 (46%) symptoms of anxiety, 163 (46%) symptoms of depression and 76 (22%) had peritraumatic distress. The mean scores of GAD-7, PHQ-9 and WHO-5 were worse in ICU HCW than in non-ICU HCW (p p Conclusion This study confirms the suspicion of a high prevalence of anxiety, depression, peritraumatic distress and low well-being during the first COVID-19 wave among HCW, especially among ICU HCW. This allows for the identification of associated risk factors. Long-term psychological follow-up should be considered for HCW.

Vasopressins are evolutionarily conserved peptide hormones. Mammalian vasopressin functions systemically as an antidiuretic and regulator of blood and cardiac flow essential for adapting to terrestrial environments. Moreover, vasopressin acts centrally as a neurohormone involved in social and parental behavior and stress response. Vasopressin synthesis in several cell types, storage in intracellular vesicles, and release in response to physiological stimuli are highly regulated and mediated by three distinct G protein coupled receptors. Other receptors may bind or cross-bind vasopressin. Vasopressin is regulated spatially and temporally through transcriptional and post-transcriptional mechanisms, sex, tissue, and cell-specific receptor expression. Anomalies of vasopressin signaling have been observed in polycystic kidney disease, chronic heart failure, and neuropsychiatric conditions. Growing knowledge of the central biological roles of vasopressin has enabled pharmacological advances to treat these conditions by targeting defective systemic or central pathways utilizing specific agonists and antagonists.

In recent decades, neighborhoods across the United States have begun to employ digital media to monitor their communities for outsiders who are seen as suspicious. Yet, little is known about these surveillance practices and their consequences at the individual and neighborhood levels. Such monitoring behaviors are important to analyze not only because of the ways that perceptions of criminal threat are often racialized but also because of the role that private citizens play in initiating contact between strangers and the police. Based on an analysis of e-mails submitted to a listserv in a liberal, predominantly white neighborhood from September 2008 through August 2009, this article explores how residents identify, discuss, and respond to people whom they define as suspicious. Findings show that most suspicious person e-mails focus on black men who are also more likely to be portrayed as unique threats to neighborhood safety. These results suggest that listserv surveillance practices foster racialized notions of criminal threat that both reinforce the boundaries of predominantly white neighborhoods and reproduce the perception of black men as criminals.

Background and Objective Intravenous (IV) infusions of telavancin for injection are generally administered in-hospital, but in some circumstances they may be administered in an outpatient environment. In that setting, antibiotics may be premixed and frozen. This study determined the chemical stability of nonpreserved telavancin in various commonly used reconstitution diluents stored in IV bags (polyvinyl chloride [PVC] and PVC-free) at −20°C (-4°F) without light. Methods Telavancin (750 mg/vial) was reconstituted with 5% dextrose injection USP (D5W) or 0.9% sodium chloride injection USP (NS) to obtain drug solutions at approximately 15 mg/mL. Infusion solutions of telavancin at diluted concentrations of 0.6 mg/mL and 8.0 mg/mL covering the range utilized in clinical practice were prepared in both PVC and PVC-free IV bags using D5W or NS solutions. The infusion solutions were stored under frozen conditions (-20°C ± 5°C [-4°F ± 41°F]) and the chemical stability was evaluated for up to 32 days. Telavancin concentration, purity, and degradant levels were determined using a stability-indicating high-performance liquid chromatography (HPLC) method. Results Telavancin IV infusion solutions in D5W or NS at 0.6 mg/mL and 8 mg/mL and stored at −20°C (-4°F) met the chemical stability criteria when tested on days 0, 7, 14, and 32. The assayed telavancin concentration at each time point was within 97% to 103% of the initial mean assay value. The total degradants quantified by the HPLC stability-indicating method did not show any significant change over the 32-day study period. Conclusion Telavancin IV infusion solutions (in D5W or NS) in both PVC and PVC-free IV bags were stable for at least 32 days when stored at −20°C (-4°F) without light. These results provide prolonged frozen stability data further to that previously established for 7 days under refrigerated conditions (2°C-8°C [36°F −46°F]), and for 12 hours at room temperature when diluted into IV bags containing D5W, NS, or lactated Ringer's solution.

BACKGROUND Planning for discharge from the hospital should begin early in each patient's stay and focus on the patient's needs. OBJECTIVE To determine how often patient-reported barriers to discharge on admission were resolved by discharge and to explore associations between barriers and readmission. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study of patients admitted to an academic medical center. INTERVENTION AND MEASUREMENTS Patients completed a barriers to discharge survey from the start of hospitalization to discharge. Primary outcomes were the prevalence of discharge barriers, rates of resolution of barriers during hospitalization, and comparisons between barriers identified in admission and discharge surveys. RESULTS One hundred sixty-three patients were enrolled, and 68 patients (42%) completed an admission survey and discharge survey ≤48 hours before discharge. Patients completed on average 1.82 surveys (standard deviation, 1.10; range, 1–8). Total and mean numbers of barriers were highest on the admission survey and decreased until the fourth survey. On average, the total number of barriers to discharge decreased by 0.15 (95% confidence interval: 0.01-0.30) per day (P = 0.047). Ninety percent of patients were discharged with at least 1 issue. The 3 most common barriers on the admission and discharge survey remained the same: pain, lack of understanding of recovery plan, and daily-living activities. CONCLUSIONS Patient-reported barriers to discharge are prevalent and incompletely addressed. This suggests an opportunity for improved discharge planning and a framework for communication between providers and patients. Journal of Hospital Medicine 2016. © 2016 Society of Hospital Medicine