Differential effects of endogenous and exogenous nitric oxide on the release of endothelin-1 from the intact perfused rat adrenal gland in situ

AbstractStudies using an inhibitor of nitric oxide (NO) synthesis have suggested that endogenous NO may have a role in regulating endothelin release. We investigated the effect of endogenous and exogenous nitric oxide (NO) on the release of irET-1. l-NAME stimulated, but l-arginine inhibited irET-1 release. Perfusing sodium nitroprusside (SNP), however, did not inhibit irET-1 secretion. CyclicGMP, the second messenger for NO action, was stimulated by SNP but not by l-arginine. These data demonstrate that endogenous NO inhibits of irET-1, in a manner which is independent of cGMP, and suggest that this action may contribute to the vasodilatory effect of NO

Site assessment of Douglas Shoal ship grounding in the Great Barrier Reef

The bulk carrier Shen Neng 1 ran aground on Douglas Shoal in the Great Barrier Reef Marine Park in April 2010. At over 40 hectares, this is the largest ship grounding scar known in the Great Barrier Reef, and possibly the largest reef-related grounding in the world. Challenges for assessment of the site included its large scale and the remote nature of Douglas Shoal coupled with its high exposure to wind, wave conditions and fauna that may pose safety hazards. Marine surveys used multiple and novel methods including sediment sampling combined with visual and acoustic survey techniques

Spin Structure of the Pion in a Light-Cone Representation

The spin structure of the pion is discussed by transforming the wave function for the pion in the naive quark model into a light-cone representation. It is shown that there are higher helicity ($\lambda_{1}+\lambda_{2}=\pm1$) states in the full light-cone wave function for the pion besides the ordinary helicity ($\lambda_{1}+\lambda_{2}=0$) component wave functions as a consequence from the Melosh rotation relating spin states in light-front dynamics and those in instant-form dynamics. Some low energy properties of the pion, such as the electromagnetic form factor, the charged mean square radius, and the weak decay constant, could be interrelated in this representation with reasonable parameters.Comment: 15 Latex pages, 2 figures upon reques

Curved Tails in Polymerization-Based Bacterial Motility

The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2

COVID-19 vaccine safety in Scotland - background rates of adverse events of special interest

Objectives: Mass COVID-19 vaccination commenced in December 2020 in Scotland. Monitoring vaccine safety relies on accurate background incidence rates (IRs) for health outcomes potentially associated with vaccination. This study aimed to quantify IRs in Scotland of adverse events of special interest (AESI) potentially associated with COVID-19 vaccination. Study design and methods: IRs and 95% confidence intervals (CIs) for 36 AESI were calculated retrospectively for the pre-COVID-19 pandemic period (01 January 2015–31 December 2019) and the COVID-19 pandemic period (01 April 2020–30 November 2020), with age-sex stratification, and separately by calendar month and year. Incident cases were determined using International Classification of Diseases-10th Revision (ICD-10)–coded hospitalisations. Results: Prepandemic population-wide IRs ranged from 0.4 (0.3–0.5 CIs) cases per 100,000 person-years (PYRS) for neuromyelitis optica to 478.4 (475.8–481.0 CIs) cases per 100,000 PYRS for acute renal failure. Pandemic population-wide IRs ranged from 0.3 (0.2–0.5 CIs) cases per 100,000 PYRS for Kawasaki disease to 483.4 (473.2–493.7 CIs) cases per 100,000 PYRS for acute coronary syndrome. All AESI IRs varied by age and sex. Ten AESI (acute coronary syndrome, acute myocardial infarction, angina pectoris, heart failure, multiple sclerosis, polyneuropathies and peripheral neuropathies, respiratory failure, rheumatoid arthritis and polyarthritis, seizures and vasculitis) had lower pandemic than prepandemic period IRs overall. Only deep vein thrombosis and pulmonary embolism had a higher pandemic IR. Conclusion: Lower pandemic IRs likely resulted from reduced health-seeking behaviours and healthcare provision. Higher IRs may be associated with SARS-CoV-2 infections. AESI IRs will facilitate future vaccine safety studies in Scotland

Factors and expectations influencing concussion disclosure within NCAA Division I athletes: A mixed methodological approach

Background: Participation in sports is associated with many benefits to all aspects of health; however, it also comes with the risk of injury, particularly concussions. Self-disclosure and care seeking following a concussion are especially important because of the lack of outwardly visible signs and/or symptoms. Although recent research has explored factors affecting concussion disclosure, use of isolated methodologies limits the ability to contextualize how disclosure or nondisclosure occurs. Therefore, the purpose of this study was to describe the factors and expectations of National Collegiate Athletic Association (NCAA) athletes that may influence concussion disclosure. Methods: This mixed-methods convergent parallel research study included 25 NCAA Division I athletes representing 13 sports, all of whom completed a concussion-education session with pre-/post-test surveys and a semistructured interview. Eligible athletes were at least 18 years old and on an NCAA roster. The surveys focused on previous concussion-related disclosure behaviors, knowledge, attitudes, beliefs, norms, and intentions about disclosing concussion. Interviews focused on the athletes’ experiences related to concussion disclosure. Survey data were analyzed using descriptive statistics and Mann-Whitney U tests. Interviews were analyzed using a Consensual Qualitative Research tradition. Results: Participants had good concussion knowledge (median = 46.0), positive attitudes (median = 38.0), strong beliefs (median = 13.0), and strong intentions to disclose concussion symptoms (median = 7.0). None of the constructs differed by participants’ gender. Although quantitative findings were mostly positive, interview data highlighted factors that may explain why some participants are successful in disclosing concussions and why others may find disclosure difficult. Educational efforts, sport culture, and medical professional presence were the primary facilitators discussed by participants. Stigma, pressure, and a lack of team support were perceived as disclosure barriers. Conclusion: The context in which concussion disclosure occurs or does not occur is vital to the success of educational interventions. Interventions must prioritize stakeholder- and team-based perspectives on concussion to establish a network supportive to disclosure

Interferon and Ribavirin Combination Treatment Synergistically Inhibit HCV Internal Ribosome Entry Site Mediated Translation at the Level of Polyribosome Formation

Purpose:Although chronic hepatitis C virus (HCV) infection has been treated with the combination of interferon alpha (IFN-α) and ribavirin (RBV) for over a decade, the mechanism of antiviral synergy is not well understood. We aimed to determine the synergistic antiviral mechanisms of IFN-α and RBV combination treatment using HCV cell culture.Methods:The antiviral efficacy of IFN-α, RBV alone and in combination was quantitatively measured using HCV infected and replicon cell culture. Direct antiviral activity of these two drugs at the level of HCV internal ribosome entry site (IRES) mediated translation in Huh-7 cell culture was investigated. The synergistic antiviral effect of IFN-α and RBV combination treatment was verified using both the CalcuSyn Software and MacSynergy Software.Results:RBV combination with IFN-α efficiently inhibits HCV replication cell culture. Our results demonstrate that IFN-α, interferon lambda (IFN-λ) and RBV each inhibit the expression of HCV IRES-GFP and that they have a minimal effect on the expression of GFP in which the translation is not IRES dependent. The combination treatments of RBV along with IFN-α or IFN-λ were highly synergistic with combination indexes <1. We show that IFN-α treatment induce levels of PKR and eIF2α phosphorylation that prevented ribosome loading of the HCV IRES-GFP mRNA. Silencing of PKR expression in Huh-7 cells prevented the inhibitory effect of IFN-α on HCV IRES-GFP expression. RBV also blocked polyribosome loading of HCV-IRES mRNA through the inhibition of cellular IMPDH activity, and induced PKR and eIF2α phosphorylation. Knockdown of PKR or IMPDH prevented RBV induced HCV IRES-GFP translation.Conclusions:We demonstrated both IFN-α and RBV inhibit HCV IRES through prevention of polyribosome formation. The combination of IFN-α and RBV treatment synergistically inhibits HCV IRES translation via using two different mechanisms involving PKR activation and depletion of intracellular guanosine pool through inhibition of IMPDH

Determinants of intention to disclose concussion symptoms in a population of U.S. military cadets

Objectives: Non-disclosure of concussion complicates concussion management, but almost nothing is known about non-disclosure in military settings. This study describes concussion disclosure-related knowledge, attitudes, perceived social norms, perceived control, and intention. Additionally, the study identifies determinants of high intention to disclose concussion symptoms. Design: Cross sectional survey. Methods: First-year service academy cadets completed a cross-sectional survey to assess perceptions of concussion disclosure. Independent variables included: gender, race, ethnicity, high school athlete status, NCAA athlete status, previous concussion history, previous concussion education, socioeconomic proxy, concussion-related knowledge, attitudes about concussion, perceived social norms (perceived peer/organizational support and actions), and perceived control over disclosure. Log-binomial regression was used to identify determinants of high intention to disclose concussion symptoms. Results: A total of 972 first-year military service academy cadets completed the survey [85% response; age = 18.4 ± 0.9 y]. In the simple models, previous concussion history was associated with lower intention to disclose concussion symptoms. High perceived control over disclosure, higher concussion knowledge, more favorable attitudes and social norms about concussion were associated with high intention to disclose. In the multivariable model, a 10% shift towards more favorable perceived social norms (PR = 1.28; p < 0.001) and attitudes (PR = 1.07; p = 0.05) about concussion were associated with high intention to disclose concussion symptoms. High perceived control over disclosure was associated with high intention to disclose concussion symptoms (PR = 1.39; p = 0.08). Conclusions: Concussion-related perceived social norms, attitudes, and perceived control are associated with intention to disclose. Organizationally appropriate intervention strategies can be developed from these data

Perceived social norms and concussion-disclosure behaviours among first-year NCAA student-athletes: implications for concussion prevention and education

Timely disclosure and identification of concussion symptoms are essential to proper care. Perceived social norms are a potential driving factor in many health-related decisions. The study purpose was to describe concussion disclosure behaviours and identify the association between perceived social norms and these disclosure behaviours. First-year student-athletes (n = 391) at two NCAA institutions completed a cross-sectional survey about concussion disclosure and disclosure determinants. Log-binomial regression models identified factors associated with concussion disclosure behaviour prevalence for: higher intention to disclose symptoms, disclosed all at time of injury, eventually disclosed all, and never participated with concussion symptoms. More favourable perceived social norms were associated with higher prevalence of intention to disclose (PR = 1.34; 95%CI: 1.18, 1.53) and higher prevalence of never participating in sports with concussion symptoms (PR = 1.50; 95%CI: 1.07, 2.10). Clinicians, coaches, sports administrators, and healthcare practitioners should be mindful of the need to create supportive social environments to improve concussion symptom disclosure