De novo human angiotensin-converting enzyme 2 decoy NL-CVX1 protects mice from severe disease after severe acute respiratory syndrome Coronavirus 2 infection

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections.This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements number 852985.info:eu-repo/semantics/publishedVersio

De novo human angiotensin - converting enzyme 2 Decoy NL-CVX1 protects mice from severe disease after severe acute respiratory syndrome coronavirus 2 infection

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections.info:eu-repo/semantics/publishedVersio

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The Voices of Native Hawaiian Women: Perceptions, Responses and Needs Regarding Intimate Partner Violence

Abstract Using a community based participatory approach, individual interviews and focus groups were conducted with Native Hawaiian women to understand their cultural perceptions, responses, and needs regarding intimate partner violence (IPV). Semi-structured interview guides were used for both interviews. The overriding theme derived from content analysis is that IPV "starts in the home," it is learned in the family and in the community. Visible injuries requiring emergency care is commonly perceived as IPV. The response to IPV included a primary theme of "defend the collective." Intimate partner violence is understood to be a "family matter," dealt within the family or by oneself. Native Hawaiian women who participated in this study sought to re-connect or establish relationships with self, others, spirit, natural elements, cultural practices, and community. Responding to IPV requires an understanding of cultural perceptions, responses, and needs of Native Hawaiians, with implications for families and communities. The needs expressed by Native Hawaiian participants reflect what they need to access "health." Implications for health care providers require understanding how best to facilitate an individual's access to "health" vs. access to "health care.&quot

SYSTEM ANALYSIS OF THE ARMY COMMUNICATION NETWORK IN SUPPORT OF ENHANCED RECRUITING

Methods of communication have increased greatly over the past 25 years. Faster, more targeted communication enables organizations to influence their audience with greater precision and achieve their effect with greater impact on those receiving the message. Communication has moved from the days of broadcasting (equivalent to the basic "dumb bomb") to targeted messaging aimed at specific groups or even individuals (equivalent to today's precision-guided munitions [PGM]). Targeted information is a "PGM" the Army can use to achieve a number of desired goals if that "weapon" is employed properly. Recruiting is a prime example of where precisely targeted communication can benefit the Army. The communications network, which includes messages, mediums, outlets, and audience, is a system that can be analyzed at its nodes and arc capacitance. Moreover, the operational effectiveness of the system is an area of analysis that will have an impact on the design and development of the network.Civilian, Department of the ArmyCivilian, Department of the ArmyCivilian, Department of the ArmyCivilian, Department of the ArmyCivilian, Department of the ArmyCivilian, Department of the ArmyApproved for public release. Distribution is unlimited

Effect of Antibiotic Duration in Emergency General Surgery Patients with Intra-Abdominal Infection Managed with Open vs Closed Abdomen

BACKGROUND: Data on duration of antibiotics in patients managed with an open abdomen (OA) due to intra-abdominal infection (IAI) are scarce. We hypothesized that patients with IAI managed with OA rather than closed abdomen (CA) would have higher rates of secondary infections (SIs) independent of the duration of the antibiotic treatment. METHODS: This was an observational, prospective, multicenter, international study of patients with IAI requiring laparotomy for source control. Demographic and antibiotic duration values were collected. Primary outcomes were SI (surgical site, bloodstream, pneumonia, urinary tract) and mortality. Statistical analysis included ANOVA, chi-square/Fisher\u27s exact test, and logistic regression. RESULTS: Twenty-one centers contributed 752 patients. The average age was 59.6 years, 43.6% were women, and 43.9% were managed with OA. Overall mortality was 16.1%, with higher rates among OA patients (31.6% vs 4.4%, p \u3c 0.001). OA patients had higher Sequential Organ Failure Assessment (4.7 vs 1.8, p \u3c 0.001), American Society of Anesthesiologists Physical Status (3.6 vs 2.7, p \u3c 0.001), and APACHE II scores (16.1 vs 9.4, p \u3c 0.001). The mean duration of antibiotics was 6.5 days (8.0 OA vs 5.4 CA, p \u3c 0.001). A total of 179 (23.8%) patients developed SI (33.1% OA vs 16.8% CA, p \u3c 0.001). Longer antibiotic duration was associated with increased rates of SI: 1 to 2 days, 15.8%; 3 to 5 days, 20.4%; 6 to 14 days, 26.6%; and more than 14 days, 46.8% (p \u3c 0.001). CONCLUSIONS: Patients with IAI managed with OA had higher rates of SI and increased mortality compared with CA. A prolonged duration of antibiotics was associated with increased rates of SI. Increased antibiotic duration is not associated with improved outcomes in patients with IAI and OA

Pediatric cryptosporidiosis: An evaluation of health care and societal costs in Peru, Bangladesh and Kenya

<div><p><i>Cryptosporidium</i> is a leading cause of pediatric diarrhea in resource-limited settings; yet, few studies report the health care costs or societal impacts of this protozoan parasite. Our study examined direct and indirect costs associated with symptomatic cryptosporidiosis in infants younger than 12 months in Kenya, Peru and Bangladesh. Inputs to the economic burden model, such as disease incidence, population size, health care seeking behaviour, hospital costs, travel costs, were extracted from peer-reviewed literature, government documents, and internationally validated statistical tools for each country. Indirect losses (i.e. caregiver income loss, mortality, and growth faltering) were also estimated. Our findings suggest that direct treatment costs per symptomatic cryptosporidiosis episode were highest in Kenya ($59.01), followed by Peru ($23.32), and Bangladesh ($7.62). The total annual economic impacts for the 0–11 month cohorts were highest in Peru ($41.5M; range $0.88-$599.3M), followed by Kenya ($37.4M; range$1.6-$804.5M) and Bangladesh ($9.6M, range $0.28-$91.5M). For all scenarios, indirect societal costs far outweighed direct treatment costs. These results highlight the critical need for innovative improvements to current prevention, diagnostic and treatment strategies available in resource poor settings, as well as the need for solutions that span multiple disciplines including food and water safety, sanitation and livestock production.</p></div