17Beta-estradiol Increases Basal But not Bradykinin-stimulated Release of Active t-PA in Young Postmenopausal Women

Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17beta-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2+/-2.3 years) who were randomized to receive 17beta-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before and during intraarterial enalaprilat (0.33 microg/min/100 mL forearm volume). 17Beta-estradiol significantly reduced baseline venous plasminogen activator inhibitor-1 antigen (4.4+/-1.4 versus 10.4+/-2.5 ng/mL, P=0.001) and t-PA antigen (5.5+/-0.6 versus 7.5+/-1.3 ng/mL, P=0.022) compared with placebo. 17Beta-estradiol increased basal forearm vascular release of active t-PA compared with placebo (1.2+/-0.3 IU/mL/min versus 0.4+/-0.1 IU/mL/min respectively, P=0.032), without increasing t-PA antigen release (P=0.761). Enalaprilat significantly increased basal net t-PA antigen release (from -0.8+/-1.0 to 3.2+/-1.2 ng/min/100 mL, P=0.012), but not the release of active t-PA, during either placebo or 17beta-estradiol. Enalaprilat potentiated bradykinin-stimulated vasodilation and t-PA antigen and activity release similarly during placebo and 17beta-estradiol treatment. 17Beta-estradiol treatment does not alter the effect of angiotensin-converting enzyme inhibition on basal t-PA antigen or on bradykinin-stimulated t-PA antigen or activity release. 17Beta-estradiol increases basal release of active t-PA in young postmenopausal women, consistent with enhanced vascular fibrinolytic function

Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-dependent Vasodilation During Angiotensin-converting Enzyme Inhibition

To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1+9/-9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/-9:-9/-9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4+/-2.8, 113.8+/-1.8, and 110.6+/-1.8 mm Hg in +9/+9, +9/-9, and -9/-9 groups, respectively; P=0.007). In the absence of enalaprilat, bradykinin-stimulated forearm blood flow, forearm vascular resistance, and net t-PA release were similar among genotype groups. Enalaprilat increased basal forearm blood flow (P=0.002) and decreased basal forearm vascular resistance (P=0.01) without affecting blood pressure. Enalaprilat enhanced the effect of bradykinin on forearm blood flow, forearm vascular resistance, and t-PA release (all P\u3c0.001). During enalaprilat, forearm blood flow was significantly lower and forearm vascular resistance was higher in response to bradykinin in the +9/+9 compared with +9/-9 and -9/-9 genotype groups (P=0.04 for both). t-PA release tended to be decreased in response to bradykinin in the +9/+9 group (P=0.08). When analyzed separately by gender, BE1 genotype was associated with bradykinin-stimulated t-PA release in angiotensin-converting enzyme inhibitor-treated men but not women (P=0.02 and P=0.77, respectively), after controlling for body mass index. There was no effect of BE1 genotype on responses to the bradykinin type 2 receptor-independent vasodilator methacholine during enalaprilat. In conclusion, the BDKRB2 BE1 polymorphism influences bradykinin type 2 receptor-mediated vasodilation during angiotensin-converting enzyme inhibition

Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data

Accurate and representative data is vital for precisely reporting the impact of influenza in healthcare systems. Northern hemisphere winter 2022/23 experienced the most substantial influenza wave since the COVID-19 pandemic began in 2020. Simultaneously, new data streams become available within health services because of the pandemic. Comparing these data, surveillance and administrative, supports the accurate monitoring of population level disease trends. We analysed admissions rates per capita from four different collection mechanisms covering National Health Service hospital Trusts in England over the winter 2022/23 wave. We adjust for difference in reporting and extracted key epidemic characteristics including the maximum admission rate, peak timing, cumulative season admissions and growth rates by fitting generalised additive models at national and regional levels. By modelling the admission rates per capita across surveillance and administrative data systems we show that different data measuring the epidemic produce different estimates of key quantities. Nationally and in most regions the data correspond well for the maximum admission rate, date of peak and growth rate, however, in subnational analysis discrepancies in estimates arose, particularly for the cumulative admission rate. This research shows that the choice of data used to measure seasonal influenza epidemics can influence analysis substantially at sub-national levels. For the admission rate per capita there is comparability in the sentinel surveillance approach (which has other important functions), rapid situational reports, operational databases and time lagged administrative data giving assurance in their combined value. Utilising multiple sources of data aids understanding of the impact of seasonal influenza epidemics in the population

Biosecurity and the ornamental fish trade: A stakeholder perspective in England

The freshwater and marine ornamental fish industry is a primary route of hazard introduction and emergence, including aquatic animal diseases and non-native species. Prevention measures are key to reducing the risk of hazard incursion and establishment, but there is currently little understanding of the biosecurity practices and hazard responses implemented at post-border stages of the ornamental fish supply chain. This study addresses this knowledge gap, using questionnaires to collate information on actual biosecurity behaviours and hazard responses practised by ornamental fish retailers and hobbyist communities in England. Actual behaviours varied considerably within retailers and hobbyists, suggesting that reliance on preventative practices by individuals in the post-border stages of the ornamental fish supply chain is likely to be ineffective in minimizing the risk of hazard incursion and establishment. Resources should be allocated towards improving and enforcing robust pre- and at-border control measures, such as risk-based surveillance of ornamental fish imports at border controls. In addition, these findings should be used to implement targeted awareness-raising campaigns and help create directed training on biosecurity practices for individuals involved in the post-border stages of the ornamental supply chain

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Habitat features influencing jaguar Panthera onca (Carnivora: Felidae) occupancy in Tortuguero National Park, Costa Rica

Habitat characteristics and human activities are known to play a major role in the occupancy of jaguars Panthera onca across their range, however the key variables influencing jaguar distribution in Tortuguero National Park, Costa Rica, have yet to be identified. This study evaluated jaguar occupancy in Tortuguero National Park and the surrounding area. Jaguar detection/non-detection data was collected using digital camera traps distributed within the boundaries of the protected area. Local community members were also interviewed to determine jaguar occurrence in the Park's buffer zone. Occupancy models were then applied to identify the habitat characteristics that may better explain jaguar distribution across the study area. From June 2012 to June 2013, a total of 4 339 camera trap days were used to identify 18 individual jaguars inside the protected area; 17 of these jaguars were exclusively detected within the coastal habitat, whilst the remaining individual was detected solely within the interior of the Park. Interviewees reported 61 occasions of jaguar presence inside the buffer zone, between 1995 and 2013, with 80% of these described by the communities of Lomas de Sierpe, Barra de Parismina and La Aurora. These communities also reported the highest levels of livestock predation by jaguars (85% of attacks). In the study area, jaguar occurrence was positively correlated with the seasonal presence of nesting green turtles Chelonia mydas, and negatively correlated with distance to the Park boundary. Our findings suggested that the current occupancy of the jaguar in the study area may be a response to: 1) the vast availability of prey (marine turtles) on Tortuguero beach, 2) the decline of its primary prey species as a result of illegal hunting inside the Park, and 3) the increase in anthropogenic pressures in the Park boundaries. Stephanny Arroyo-Arce1*, James Guilder2 & Roberto Salom-Pérez3 1Instituto Internacional en Conservación y Manejo de Vida Silvestre, Universidad Nacional, 1350-3000 Heredia, Costa Rica; [email protected] Vision International/GVI Costa Rica, 230-60601 Quepos, Costa Rica; [email protected] Costa Rica, 8-3870-1000 San José, Costa Rica; [email protected]* Correspondenc

Production without medicalisation : Risk practices and disease in Bangladesh aquaculture

Improved biosecurity and livestock disease control measures in low resource settings are often regarded as beneficial for agricultural productivity, rural incomes, global health, and sustainability. In this paper we present data from a study of shrimp and prawn aquaculture in Bangladesh to argue that this relationship is not as straightforward as it would seem. Analysing quantitative and qualitative data from a multi‐method field study involving 300 “missing middle” farmers, we demonstrate the importance of socio‐economic and ecological conditions to any disease management strategy. We describe how a technical programme to introduce “disease‐free” seed faltered partly as a result of the farmers' tendency to offset disease and livelihood risks by frequently re‐stocking their ponds. Changes to seed provision were accompanied by calls to alter farmers' livestock production practices. Paradoxically, these changes exposed farmers to more intense risks, potentially locking them into unsustainable disease management practices. The analysis emphasises that vernacular farming practices should be considered as key assets rather than barriers to disease management strategies, and that closer attention be paid to value chain and other risks as drivers of unsustainable practices.Peer reviewe

Jaguars (Panthera onca) increase kill utilization rates and share prey in response to seasonal fluctuations in nesting green turtle (Chelonia mydas mydas) abundance in Tortuguero National Park, Costa Rica

Jaguar (Panthera onca) predation of green turtles (Chelonia mydas mydas) is now a common occurrence in Tortuguero National Park, Costa Rica. The abundance of green turtles during nesting season ensures a constant provision of easy and predictable prey, however it is unknown to what extent jaguars con sume turtle carcasses and how the jaguar population responds to limited turtle availability outside of nesting season. This study took advantage of the accessible nature of jaguar-predated turtle carcasses on Tortuguero Beach over a two year period (2011–2013), to provide a novel analysis of carcass utiliza tion rates by jaguars and determine the effects of temporal fluctuations in green turtle nesting numbers. Camera traps were set-up on freshly predated turtles to capture jaguar activity across both Peak and Non Peak green turtle nesting seasons. Thirteen individual jaguars (five males, five females, three cubs) were captured returning to 77% of monitored turtle kills (60% Peak; 95% Non Peak). During Non Peak season, the number of jaguars per kill increased (H(1) = 15.91, p < 0.001) and total jaguar feeding time per kill also increased (H(1) = 13.34, p < 0.001). The propensity for tolerated scavenging or sharing during Non Peak season is illustrated by four adult jaguars captured interacting with a kill at separate times over two nights in October, 2012 (two males, two females). There were no significant differences between males and females, although there is a tendency for the latter to handle the prey to a greater extent. Although marine turtles may notto be a primary prey species,they play an important role in subsidizing the jaguars in this study. The increased kill utilization rates and prey sharing displayed by the jaguars, ensures opti mal foraging during periods of low prey availability. These apparently atypical feeding behaviors may be unique to Tortuguero, however their prevalence across the jaguar’s range should be considered. © 2014 Deutsche Gesellschaft für Säugetierkunde. Published by Elsevier GmbH. All rights reserved.Universidad Nacional, Costa Rica.Instituto Internacional en Conservación y Manejo de Vida Silvestr

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