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51.
Association between CFH,CFB, ARMS2, SERPINF1, VEGFR1 and VEGF polymorphisms and anatomical and functional response to ranibizumab treatment in neovascular age‐related macular degeneration 下载免费PDF全文
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Alfredo Oliveros Ki Hyun Yoo Mohammad Abdur Rashid Ana Corujo-Ramirez Benjamin Hur Jaeyun Sung Yuanhang Liu John R. Hawse Doo-Sup Choi Detlev Boison Mi-Hyeon Jang 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(28)
Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A2A receptor (A2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A2AR inhibition by the Food and Drug Administration–approved A2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments. 相似文献
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Amy C. Morrison Robert C. Reiner Jr. William H. Elson Helvio Astete Carolina Guevara Clara del Aguila Isabel Bazan Crystyan Siles Patricia Barrera Anna B. Kawiecki Christopher M. Barker Gissella M. Vasquez Karin Escobedo-Vargas Carmen Flores-Mendoza Alfredo A. Huaman Mariana Leguia Maria E. Silva Sarah A. Jenkins Wesley R. Campbell Eugenio J. Abente Robert D. Hontz Valerie A. Paz-Soldan John P. Grieco Neil F. Lobo Thomas W. Scott Nicole L. Achee 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(26)
Over half the world’s population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito–human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = −9.11) and 12.4% (95% CI 4.2%, ∞); z = −2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.Aedes-borne viral diseases (ABVDs) [e.g., dengue (DENV), chikungunya, Zika (ZIKV), and yellow fever] are devastating, expanding global public health threats that disproportionally affect low- and middle-income countries. DENV, one of the most rapidly increasing vector-borne infectious diseases, results in ∼400 million infections each year (1, 2), with 4 billion people at risk for infection annually (3). Currently, the primary means for ABVD prevention is controlling the primary mosquito vector, Aedes aegypti. Existing vector control interventions, however, have failed to prevent ABV transmission and epidemics (4–6).There is an urgent need to develop evidence-based guidance for the use of new and existing ABV vector control tools. The evidence base for vector control against ABVs is weak, despite considerable government investments in World Health Organization (WHO)-recommended control of larval habitats (larviciding, container removal) and ultra-low-volume insecticide spraying (4, 5, 7–9). These strategies continue to be implemented despite the lack of rigorously generated data from controlled clinical trials demonstrating they reduce ABV infection or disease (6). The only ABV intervention with a proven epidemiological impact in a cluster-randomized control trial (cRCT) assessed community mobilization to reduce mosquito larval habitats (10). A recent test-negative trial with Wolbachia-infected mosquitoes reported a significant reduction of DENV illness in Indonesia (11).Spatial repellents (SRs) are devices that contain volatile active ingredients that disperse in air. The active ingredients can repel mosquitoes from entering a treated space, inhibit attraction to human host cues, or disrupt mosquito biting and blood-feeding behavior and, thus, interfere with mosquito–human contact (12–14). Any of these outcomes reduce the probability of pathogen transmission. Pyrethroid-based SRs have shown efficacy in reducing malaria infections in China (15) and Indonesia (16). There have, however, been no clinical trials evaluating the protective efficacy (PE) of SRs against ABV infection or disease.To generate evidence for public health consideration, we conducted a double-blinded, parallel cRCT to demonstrate and quantify the PE of a transfluthrin-based SR to reduce ABV infection incidence over 2 y in a human cohort in Iquitos, Peru. 相似文献
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Redondo Alfredo Paradela-Dobarro Beatriz Moscoso Isabel Moure-Álvarez María Cebro-Márquez María González-Juanatey José Ramón García-Seara Javier Álvarez Ezequiel 《Journal of molecular medicine (Berlin, Germany)》2021,99(7):955-956
Journal of Molecular Medicine - A Correction to this paper has been published: https://doi.org/10.1007/s00109-021-02062-6 相似文献
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Ferdinando Carlo Sasso Pia Clara Pafundi Alfredo Caturano Raffaele Galiero Erica Vetrano Riccardo Nevola Salvatore Petta Anna Ludovica Fracanzani Carmine Coppola Vito Di Marco Antonio Solano Rosa Lombardi Mauro Giordano Antonio Craxi Alessandro Perrella Celestino Sardu Raffaele Marfella Teresa Salvatore Luca Rinaldi 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2021,31(8):2345-2353
Background and aimsBeyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort.Methods and resultsIn this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19–34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148–1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44–53.95; p = 0.016).ConclusionsHCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors. 相似文献
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Diego Penela Cheryl Teres Juan Fernández-Armenta Luis Aguinaga Luis Tercedor David Soto-Iglesias Beatriz Jauregui Augusto Ordóñez Juan Acosta Felipe Bisbal Marta Aceña Etelvino Silva Alfredo Chauca Francesco De Sensi Radu Vatasescu Pablo Sánchez-Millán Julio Carballo Lluis Mont Antonio Berruezo 《Heart rhythm》2021,18(1):27-33
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