Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice

Activation of the hypothalamic-pituitary-adrenal axis results in the release of hormones from the adrenal glands, including glucocorticoids and mineralocorticoids. The physiological association between corticosteroids and cardiac disease is becoming increasingly recognized; however, the mechanisms underlying this association are not well understood. To determine the biological effects of corticosteroids on the heart, we investigated the impact of adrenalectomy in C57BL/6 male mice. Animals were adrenalectomized (ADX) at 1 month of age and maintained for 3–6 months after surgery to evaluate the effects of long-term adrenalectomy on cardiac function. Morphological evaluation suggested that ADX mice showed significantly enlarged hearts compared with age-matched intact controls. These changes in morphology correlated with deficits in left ventricular (LV) function and electrocardiogram (ECG) abnormalities in ADX mice. Correlating with these functional defects, gene expression analysis of ADX hearts revealed aberrant expression of a large cohort of genes associated with cardiac hypertrophy and arrhythmia. Combined corticosterone and aldosterone replacement treatment prevented the emergence of cardiac abnormalities in ADX mice, whereas corticosterone replacement prevented the effects of adrenalectomy on LV function but did not block the emergence of ECG alterations. Aldosterone replacement did not preserve the LV function but prevented ECG abnormalities. Together, the data indicate that adrenal glucocorticoids and mineralocorticoids either directly or indirectly have selective effects in the heart and their signaling pathways are essential in maintaining normal cardiac function

Quiet Supersonic Flights 2018 (QSF18) Test: Galveston, Texas Risk Reduction for Future Community Testing with a Low-Boom Flight Demonstration Vehicle

The Quiet Supersonic Flights 2018 (QSF18) Program was designed to develop tools and methods for demonstration of overland supersonic flight with an acceptable sonic boom, and collect a large dataset of responses from a representative sample of the population. Phase 1 provided the basis for a low amplitude sonic boom testing in six different climate regions that will enable international regulatory agencies to draft a noise-based standard for certifying civilian supersonic overland flight. Phase 2 successfully executed a large scale test in Galveston, Texas, developed well documented data sets, calculated dose response relationships, yielded lessons, and identified future risk reduction activities

Work-related and personal factors associated with mental well-being during the COVID-19 response: Survey of health care and other workers

BACKGROUND: The response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an unprecedented disruption in work conditions. This study describes the mental health and well-being of workers both with and without clinical exposure to patients with coronavirus disease (COVID-19). OBJECTIVE: The aim of this study is to measure the prevalence of stress, anxiety, depression, work exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic and describe work-related and personal factors associated with their mental health and well-being. METHODS: All faculty, staff, and postdoctoral fellows of a university, including its medical school, were invited in April 2020 to complete an online questionnaire measuring stress, anxiety, depression, work exhaustion, burnout, and decreased well-being. We examined associations between these outcomes and factors including work in high-risk clinical settings and family/home stressors. RESULTS: There were 5550 respondents (overall response rate of 34.3%). Overall, 34% of faculty and 14% of staff (n=915) were providing clinical care, while 61% of faculty and 77% of staff were working from home. Among all workers, anxiety (prevalence ratio 1.37, 95% CI 1.09-1.73), depression (prevalence ratio 1.28, 95% CI 1.03-1.59), and high work exhaustion (prevalence ratio 1.24, 95% CI 1.13-1.36) were independently associated with community or clinical exposure to COVID-19. Poor family-supportive behaviors by supervisors were also associated with these outcomes (prevalence ratio 1.40, 95% CI 1.21-1.62; prevalence ratio 1.69, 95% CI 1.48-1.92; and prevalence ratio 1.54, 95% CI 1.44-1.64, respectively). Age \u3c40 years and a greater number of family/home stressors were also associated with these poorer outcomes. Among the subset of clinicians, caring for patients with COVID-19 and working in high-risk clinical settings were additional risk factors. CONCLUSIONS: Our findings suggest that the pandemic has had negative effects on the mental health and well-being of both clinical and nonclinical employees. Mitigating exposure to COVID-19 and increasing supervisor support are modifiable risk factors that may protect mental health and well-being for all workers

Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease

Effect of Ozone and Calcium Lactate Treaments on Browning and Textured Properties of Fresh-Cut Lettuce

The effects of three treatments, 1 mg L−1 ozone at 18–20 °C, 15 g L−1 calcium lactate (CLac) at 50 °C and a combination thereof, were compared on fresh-cut lettuce over 10 days of refrigerated storage. Respiration rate, browning and texture were examined as main quality indicators. The use of ozone produced a significantly (P \u3c 0.05) higher oxygen decline than the use of CLac (from day 3 to day 10). At the end of storage, CLac (alone or combined with ozone) samples had higher oxygen content (∼9%) than ozone samples (∼6%). Enzymatic activity decreased significantly (P \u3c 0.05) in ozone samples. Polyphenol oxidase activity in fresh-cut lettuce treated with ozone (alone or combined with CLac) showed lower values on day 1 (−1) and at the end of storage (g−1) than CLac samples (4000–4800 units g−1). Ozone also reduced peroxidase activity to ∼300 units g−1 after treatment. Finally, pectin methylesterase activity was also reduced with ozone, showing a negative effect on textural properties. Data suggested that CLac maintained quality markers better than treatments with ozone and ozone/CLac combination over 10 days of storag

History of exotic Meson (4-quark) and Baryon (5-quark) States

I briefly review the history of exotic meson (4-quark) and baryon (5-quark) states, which is rooted in the formalism of Regge pole and duality. There are robust model-independent predictions for the exchange of 4-quark (Baryonium) Regge trajectories in several processes, which are strongly supported by experiment. On the other hand the predictions for the spectroscopy of 4-quark resonances are based on specific QCD inspired models, with some experimental support. The corresponding predictions for the recently discovered exotic baryon (Pentaquark) state are briefly discussed.Comment: 14 pages Latex including 4 eps figures, final version to appear as a topical review in J. Phys.

Developing indicators and measures of high-quality for Australian general practice

Background: Rising health costs and health inequity are major challenges in Australia, as internationally. Strong primary health care is well evidenced to address these challenges. Primary Health Networks (PHNs) work with general practices to collect data and support quality improvement; however, there is no consensus regarding what defines high quality. This paper describes the development of an evidence-based suite of indicators and measures of high-quality general practice for the Australian context. Methods: We reviewed the literature to develop a suitable framework and revise quality assurance measures currently in use, then reviewed these in three workshops with general practitioners, practice managers, nurses, consumers and PHN staff in western Sydney. We used a descriptive qualitative research approach to analyse the data. Results: A total of 125 evidence-based indicators were agreed to be relevant, and 80 were deemed both relevant and feasible. These were arranged across a framework based on the Quadruple Aim, and include structure, process and outcome measures. Conclusions: The agreed suite of indicators and measures will be further validated in collaboration with PHNs across Australia. This work has the potential to inform health systems innovation both nationally and internationally

Use of newly isolated phages for the control of Pseudomonas aeruginosa PAO1 and ATCC 10145 biofilms

Pseudomonas aeruginosa is a relevant opportunistic pathogen involved in nosocomial infections. that frequently shows low antibiotic susceptibility. One of its virulence factors is associated with the ability to adhere to surfaces and form virulent biofilms. This work describes the isolation and characterization of lytic phages capable of infecting antibiotic-resistant P. aeruginosa strains. In addition, characterization of P. aeruginosa biofilms and the potential of newly isolated phages for planktonic and biofilm control was accessed. According to the results, the isolated phages showed different spectra of activity and efficiency of lysis. Four broad lytic phages were selected for infection of planktonic cells; however, despite their broad range of activity, two of the selected phages failed to efficiently control planktonic cultures. Therefore, only two phages (phiIBB-PAA2 and phiIBB-PAP21), highly capable of causing strong biomass reduction of planktonic cells, were tested against 24 h biofilms using a m.o.i. of 1. Both phages reduced approximately 1-2 log the biofilm population after 2 h of infection and reduction was further enhanced after 6 h of biofilm infection. However, biofilm cells of P. aeruginosa PAO1 acquired resistance to phiIBB-PAP21; consequently, an increase in the number of cells after 24 h of treatment was observed. Conversely, phage phiIB-PAA2 for P. aeruginosa ATCC10145 continued to destroy biofilm cells, even after 24 h of infection. In these biofilms, phages caused a 3 log reduction in the number of viable counts of biofilm cells