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raNKl inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(raNKl)as a potential treatment *** this study,we investigated the mechanisms underlying raNKl inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after raNKl *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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Risk Factors Associated with Unsuccessful Vaginal Birth after One Cesarean (VBAC-1) in Puerto Rico

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Open Journal of Obstetrics and Gynecology 2024年第6期14卷 888-902页

作者： Irazú Guinan Marjorie Suárez Fabiola Angulo luis Mayol Paula Suárez lisandris Dominicci Nathalie Chang Saribel Torres Antonio Rodríguez raymond l. Tremblay Maricarmen Colón-Díaz Department of Physiology and Pathology San Juan Bautista School of Medicine Caguas USA

Background: Cesarean section (CS) has increased steadily over the last decade, with an estimated one-third of women delivering by cesarean section worldwide. Objective: Our study aimed to investigate the demographic and associated factors influencing vaginal birth after one cesarean (VBAC-1) success focusing on variables like pre-pregnancy BMI, diabetes, hypertension, education, and smoking. Study Design and Methods: In this retrospective study, we analyzed 285 cases (81 unsuccessful VBAC-1, 204 successful VBAC-1) from San Juan City Hospital (Puerto Rico) between January 1, 2019, and December 31, 2020. We used odds ratios and model selection comparison to assess the impact of variables on successful VBAC-1, using a significance threshold of 95% CI. Model selection assessed binomial model combinations using a generalized linear approach to identify key risk factors. Results: Unsuccessful VBAC-1 (a repeat cesarean), was associated with diabetes (OR: 0.376, p = 0.086), hypertension (OR: 0.23, p = 0.006), and university-educated women (OR: 1.372, p = 0.711). High school-educated women had an OR of 3.966 (p = 0.105), while overweight women were 0.481 times more likely to have unsuccessful VBAC-1 (p = 0.041). Significant associations were not found with obesity (OR: 0.574, p = 0.122), underweight/normal (OR: 1.01, p = 0.810), or smoking (OR: 1.227, p = 0.990). Conclusion: Results revealed women with higher education levels, hypertension, or diabetes are less likely to have a successful VBAC-1. Understanding the complex interactions affecting these outcomes is aimed at establishing guidelines for healthcare professionals to conduct systematic risk/benefit assessments. This study lays a foundation for evidence-based practices and policies, offering initial insights into VBAC-1 success factors in Puerto Rico.

关键词： Diabetes Hypertension Obesity Trial of labor Vaginal Birth after Cesarean

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C3G contributes to platelet activation and aggregation by regulating major signaling pathways

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2103-2117页

作者： Sara gutiérrez-Herrero Cristina Fernández-Infante luis Hernández-Cano Sara Ortiz-Rivero Carlos Guijas Víctor Martín-Granado Joséramón González-Porras Jesús Balsinde Almudena Porras Carmen Guerrero Instituto de Biología Molecular y Celular del Cáncer(IMBCC) University of Salamanca-CSICSalamancaSpain Instituto de Investigación Biomédica de Salamanca(IBSAl) SalamancaSpain Instituto de Biología y Genética Molecular(IBGM) Consejo Superior de Investigaciones Científicas(CSIC)University of ValladolidValladolidSpain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM) MadridSpain Departamento de Hematologiá Hospital Universitario de Salamanca(HUS)SalamancaSpain Departamento de Bioquímica y Biología Molecular Facultad de FarmaciaComplutense University of Madrid.Instituto de Investigación Sanitaria del Hospital Clínico San Carlos(IdISSC)MadridSpain Departamento de Medicina University of SalamancaSalamancaSpain

C3G is a GEF(guanine nucleotide exchange factor)for rap GTPases,among which the isoform rap1b is an essential protein in platelet *** transgenic mouse models with platelet-specific overexpression of C3G or mutant C3GΔCat,we have unveiled a new function of C3G in regulating the hemostatic function of platelets through its participation in the thrombin-PKCrap1b pathway.C3G also plays important roles in angiogenesis,tumor growth,and metastasis through its regulation of the platelet *** addition,C3G contributes to megakaryopoiesis and ***,we used a platelet-specific C3G-KO mouse model to further support the role of C3G in hemostasis.C3G-KO platelets showed a significant delay in platelet activation and aggregation as a consequence of the defective activation of rap1,which resulted in decreased thrombus formation in ***,we explored the contribution of C3G-rap1b to platelet signaling pathways triggered by thrombin,PMA or ADP,in the referenced transgenic mouse model,through the use of a battery of specific *** found that platelet C3G is phosphorylated at Tyr504 by a mechanism involving *** phosphorylation was shown to be positively regulated by ERKs through their inhibition of the tyrosine phosphatase ***,C3G participates in the ADP-P2Y12-PI3K-rap1b pathway and is a mediator of thrombin-TXA2 ***,it inhibits the synthesis of TXA2 through cPlA2 *** together,our data reveal the critical role of C3G in the main pathways leading to platelet activation and aggregation through the regulation of rap1b.

关键词： C3G platelet activation

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Epidemiology of work-related hand and wrist injuries in a referral center: A descriptive study

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World Journal of Orthopedics 2024年第7期15卷 650-659页

作者： Angélica M Rodríguez Ginna P Tocanchón Jessica T Villalba luis M Pombo Aníbal A Teherán Gabriel Camero-ramos Karen P Ayala Gerhard M Acero Research Center Fundación Universitaria Juan N.CorpasBogotá111321Colombia Red Cross Cruz Roja Colombiana-Seccional Cundinamarca BogotáBogotá111221Colombia Vigilancia Epidemiológica Instituto Nacional de SaludBogotá111321Colombia

BACKGROUND Occupational hand and wrist injuries(OHWIs)account for 25%of work-related accidents in low-and middle-income *** Colombia,more than 500000 occupational accidents occurred in 2021,and although the rate declined to less than 5%in 2020 and 2021,at least one in four accidents involved a hand or wrist *** To describe the OHWIs in workers seen at the emergency room at a second-level hospital in *** An observational study was performed using data from workers who experienced OHWIs and attended a second-level hospital,between June,2020 and May,*** overall frequency of OHWIs,as well as their distribution by sociodemo-graphic,clinical,and occupational variables,are ***,association patterns between sex,anatomical area(fingers,hand,wrist),and type of job were analyzed by correspondence analysis(CA).RESUlTS There were 2.101 workers treated for occupational accidents,423(20.3%)were cases of OHWIs,which mainly affected men(93.9%)with a median age of 31 years and who worked mainly in mining(75.9%).OHWIs were more common in the right upper extremity(55.3%)and comprised different types of injuries,such as contusion(42.1%),laceration(27.9%),fracture(18.7%),and crush injury(15.6%).They primarily affected the phalanges(95.2%),especially those of the first finger(25.7%).The CAs showed associations between the injured anatomical area and the worker’s job that differed in men and women(explained variance>90%).CONClUSION One out of five workers who suffered occupational accidents in Cundinamarca,Columbia had an OHWI,affecting mainly males employed in *** occupational profile is likely to lead to prolonged rehabilitation,and permanent functional *** results might be useful for adjusting preventive measures in cluster risk groups.

关键词： Accidents Occupational Epidemiology Hand injuries Wrist injuries Occupational health

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Deciphering the fiber quality of Gossypium barbadense *** in la Convención,Cusco,Perú

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Journal of Cotton Research 2024年第3期7卷 231-242页

作者： MOralES-AraNIBAR luis SAENZ Manuel Canto MOralES-AraNIBAR Carlos Genaro RIVEra Marite Yulisa Nieves AGUIlEra Jorge González STEINER Fábio BARDIVIESSO Diógenes Martins ZUFFO Alan Mario National Intercultural University of Quillabamba Cusco 08741Peru Universidad Nacional Agraria la Molina(UNAlM) Lima 012Peru Graduate School Jorge Basadre Grohmann National UniversityTacna 583000Peru National Institute of Agrarian Innovation(INIA) Lima 15024Peru Department of Agronomy State University of Mato Grosso do Sul(UEMS)Cassilândia 79540‑000MSBrazil Department of Agronomy State University of Maranhão(UEMA)Balsas 65800‑000MABrazil

Background The quality of cotton fiber determines its value in the textile market,influencing agricultural profitability and the efficiency of textile *** selection of genotypes with superior fibers is a key factor for genetic improvement programs seeking adaptability and sustainability in the face of climate *** demonstrates the strategic importance of this plant for sustainable agriculture and the global textile *** objective of this research was to decipher the fiber quality of Gossypium barbadense *** in the native Amazonian communities of la Convención,Cusco-Perú,and to evaluate other critical aspects of native cotton that have not yet been *** methodology included non-probability sampling for accessibility,qualitative and quantitative analyses,and multivariate *** fiber length(mm),micronaire index(maturity/fineness),fiber strength(gf/tex),length uniformity index(%),fiber elongation(%),maturation index(%),and short fiber index(%)were the fiber characteristics evaluated using the HVI method in cotton *** Cotton accessions collected from Koribeni(Gossypium spp.)and Shivankoreni(Gossypium barbadense ***)stood out for their fiber quality properties,especially length,strength,and uniformity,which highlights their relevance for advanced textile applications and potential for use in plant genetic improvement *** These findings reinforce the need to conserve and study these native cotton accessions from the Peruvian Amazon region,which can offer promising perspectives for the textile industry and agricultural biodiversity.

关键词： Cotton Sustainability Amazonian communities Cotton fiber quality

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Venopulmonary ECMO Improved Hypoxemia and Supported the Right Ventricle in a Patient with Decompensated Eisenmenger Syndrome

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World Journal of Cardiovascular Surgery 2024年第1期14卷 7-19页

作者： Daniel Manzur-Sandoval Gian Manuel Jiménez-Rodríguez Edgar García-Cruz ramón Espinosa-Soto Erika Yamali ramirez-Marcano Yessenia Máyory Téllez-lópez José luis Elizalde-Silva Gustavo Rojas-Velasco Cardiovascular Critical Care Unit Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico Adult Congenital Heart Disease Unit Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico Cardiology Department Ignacio Ch&#225vez National Institute of Cardiology Mexico City Mexico

Mechanical circulatory and/or respiratory assistance with extracorporeal membrane oxygenation (ECMO) has become a standard of care for patients with circulatory (venoarterial) and/or respiratory (venovenous) failure refractory to standard therapies. Adult patients with congenital heart disease are an increasingly recognized and growing population and include various groups, such as undiagnosed cases in childhood and palliated and/or corrected cases, which require subsequent care because of residual lesions, cardiac arrest/insufficiency, and arrhythmias, among other conditions. In addition, these patients are prone to developing pathologies that are typical of adulthood with a generally increased risk of morbidity and mortality because of their low reserves and organic damage associated with the underlying heart disease, which makes them candidates for ECMO. These patients represent an additional challenge in this therapy because malformations and the presence of a shunt can generally affect the usual cannulation methods and hemodynamic and oximetry monitoring. Thus, the configuration decision must be made on a case-by-case basis. Here, we present a cannulation method, venopulmonary artery ECMO, which provides hemodynamic and respiratory support, and may be ideal for patients with shunts and/or right ventricular dysfunction. To our knowledge, this is the first report of this configuration in patients with congenital heart diseases.

关键词： Eisenmenger Syndrome Venopulmonary Artery ECMO Refractory Hypoxemia Right Ventricular Dysfunction

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Hepatocyte culture in a radial-flow bioreactor with plasma polypyrrole coated scaffolds

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BIOCEll 2015年第2期39卷 9-14页

作者： Odin raMÍREZ-FERNÁNDEZ rafael GODÍNEZ Esmeralda ZUÑIGA-AGUIlAR luis E.GÓMEZ-QUIROZ María C.gutiÉrrez-RUIZ Juan MOralES Roberto OlAYO Departamento de Ingeniería Eléctrica Universidad Autónoma MetropolitanaUnidad IztapalapaApdo.Postal 55-534IztapalapaMéxico. Departamento de Ciencias de la Salud Universidad Autónoma MetropolitanaUnidad IztapalapaApdo.Postal 55-534IztapalapaMéxico Departamento de Física Universidad Autónoma MetropolitanaUnidad IztapalapaApdo.Postal 55-534IztapalapaMéxico

We have designed and evaluated a radial-flow bioreactor for three-dimensional liver carcinoma cell culture on a new porous coated *** designed a culture chamber where a radial flow of culture medi-um was continuously delivered through *** this system was established,flow was simulated using flow dy-namics software based on numeric methods to solve Navier-Stockes flow *** within cell culture scaffolds was simulated using a flow velocity of 7 ml/min and found that cell culture medium was distributed unhindered in the bioreactor ***,the bioreactor was built according to the simulated design and was tested with liver carcinoma cells(HepG2)cultured over an l-polylactic acid scaffold whose surface was modified with iodine-doped *** bioreactor was tested under non-flow and in radial flow *** density under radial flow conditions was almost double than that under static conditions and both total protein and albumin output was also increased under radial flow conditions.

关键词： Cell Cultures Flow Simulation Flow Features HepG2 Cells Plasma Polymerization

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Management and outcomes of patients with Crohn’s disease with first vs multiple surgeries:results from the PraCTICROHN study

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Gastroenterology Report 2019年第6期7卷 411-418,I0001,I0002页

作者： Marisa Iborra Berta Juliá Maria Dolores Martín Arranz Manuel Barreiro-de Acosta Ana gutiérrez Valle García-Sánchez Carlos Taxonera Javier P.Gisbert luis Cea-Calvo Eugeni Domènech Gastroenterology Department Hospital La FeValenciaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) MadridSpain Medical Department Merk Sharp and Dohme(MSD)MadridSpain Gastroenterology Unit Hospital Universitario La PazIdiPAZMadridSpain Gastroenterology Unit Complejo Hospitalario Universitario de SantiagoSantiago de CompostelaSpain Digestive Medicine Department Hospital General de AlicanteAlicanteSpain Unit of Clinical Management of Gastrointestinal Tract Hospital Universitario Reina SofiaMaimonides Institute of Biomedical Research of Cordoba(IMIBIC)Cordoba UniversityCordobaSpain Gastroenterology Department Hospital Clínico San CarlosMadridSpain Instituto de Investigación del Hospital Clínico San Carlos(IdISSC) MadridSpain Gastroenterology Department Hospital Universitario de La PrincesaInstituto de Investigación Sanitaria Princesa(IIS-IP)MadridSpain Gastroenterology Department Hospital Universitari Germans Trias i PujolBadalonaSpain

Background:Surgery in Crohn’s disease(CD)may be associated with poor prognosis and clinical and surgical *** aim of this study was to describe and compare the post-operative management and outcomes of patients with CD who underwent first vs recurrent ***:Observational study that included adult CD patients from 26 Spanish hospitals who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December *** were retrospectively collected from the medical ***:Data from 314 patients were analysed,of whom 262(83%)underwent first surgery and 52(17%)referred to previous CD *** characteristics were similar between the two groups except for a higher rate of stricturing behavior at diagnosis among re-operated patients(P=0.03).After surgery,a higher proportion of re-operated patients received prophylactic treatment with immunomodulators compared with patients with first surgery(P=0.04).In re-operated patients,time to clinical recurrence was not associated with the fact of receiving or not prophylaxis,whereas,in patients with first surgery,recurrence-free survival was greater when prophylaxis was received(P=0.03).Conclusions:After surgery,a higher proportion of patients with previous surgeries received prophylactic treatment with immunomodulators compared with patients with first *** prophylactic treatment was beneficial for preventing clinical recurrence in patients operated on for the first time,it did not significantly reduce the risk of further recurrence in patients with previous *** suggests that effective prophylactic therapies are still needed in this subset of patients.

关键词： Crohn’s disease surgery post-operative recurrence

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Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis

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Open Journal of Respiratory Diseases 2024年第2期14卷 39-50页

作者： Myriam Calle Rubio Olga de la Serna Blazquez José luis R. Martin Manuel Ruiz Cuetos Pulmonology Department Hospital Clínico San Carlos Madrid Spain Department of Medicine School of Medicine Universidad Complutense de Madrid Madrid Spain Instituto de Investigacion Sanitaria del Hospital Clínico San Carlos (IdISSC) Madrid Spain Pediatric Pulmonology Unit Pediatrics Department Hospital Universitario La Paz Madrid Spain Simplifying Research Institute Layos Spain Medical department in ITF Research Pharma S.l.U. Alcobendas Spain

Objective: This study aims to systematically examine the existing evidence regarding the clinical benefits of carbocysteine as an adjunctive treatment in acute bronchopulmonary and otorhinological processes. Design: Systematic review and meta-analysis. Data sources: An electronic search was conducted across PubMed, Cochrane library, ***, and the European Clinical Trial Register, with the search dated to May 2023. Bibliographic references from other literature reviews and meta-analyses were also reviewed. The search was limited to randomized clinical trials published in any language and year. It was completed by cross-checking the references of the located articles. Methods: Inclusion criteria covered studies assessing systemic or inhaled carbocysteine, regardless of dosing regimen. Concomitant medication use was acceptable if balanced between intervention and control groups. Authors independently extracted data, resolving disagreements through consensus. Methodological quality assessment relied on critical reading of each study. Dichotomous variables were analyzed using odds ratio (OR), and a final effect size was calculated. Statistical significance was established when confidence intervals did not cross the neutral value. Heterogeneity was assessed via the X2 test and I2 index. Results: Out of 318 initially identified studies, 4 met inclusion criteria. The meta-analysis for poor general condition yielded an OR of 0.45 in favor of intervention, p = 0.013, with non-significant heterogeneity. Cough events showed a percentage of 15.8% for carbocysteine vs. 27.2% for placebo. On the seventh day, expectoration rates were 18.37% for carbocysteinevs 33.3% for placebo. Conclusions: The observed clinical benefits align with carbocysteine’s mucoactive and muco-regulatory properties, complemented by anti-inflammatory and antioxidant actions. Carbocysteine stands out among mucolytic agents. In the context of persistent infectious diseases,

关键词： Acute Respiratory Infections Carbocystenine Systematic Review Meta-Analysis

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Visual perception alterations in COVID-19:a preliminary study

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International Journal of Ophthalmology(English edition) 2023年第1期16卷 1-9页

作者： María Begoña Coco-Martín luis leal-Vega Irene Alcoceba-Herrero Ainhoa Molina-Martín Dolores de-Fez María Joséluque Carlos Dueñas-gutiérrez Juan Francisco Arenillas-lara David PPiñero Group of Applied Clinical Neurosciences and Advanced Data Analysis Department of MedicineDermatology and ToxicologyUniversity of ValladolidValladolid 47005Spain Group of Optics and Visual Perception Department of OpticsPharmacology and AnatomyUniversity of AlicanteAlicante 03690Spain Department of Optics and Optometry and Vision SciencesUniversity of ValenciaValencia 46100Spain COVID-19 Unit Department of Internal MedicineUniversity Clinical Hospital of ValladolidValladolid 47003Spain Stroke Unit Department of NeurologyUniversity Clinical Hospital of ValladolidValladolid 47003Spain Clinical Optometry Unit Department of OphthalmologyVithas Medimar International HospitalAlicante 03016Spain

AIM:To compare the visual perception(color and chromatic-achromatic contrast vision)of a small cohort of COVID-19 patients at the time of infection and after 6mo with that of a healthy population matched for sex and ***:A total of 25 patients(9 females,16 males,mean age:54±10y)with COVID-19 hospitalized in the COVID-19 Unit of the University Clinical Hospital of Valladolid were recruited for this preliminary *** perception,as determined by monocular measurement of contrast sensitivity function(CSF)and color vision was assessed in each patient using the Optopad *** results obtained were then compared with those of a sample of 16 age-and sex-matched healthy controls(5 females,11 males,mean age:50±6y)in which the same measurement procedure was *** significant differences between groups were assessed using the Mann-Whitney U *** were repeated after a minimum follow-up period of 6mo and statistically significant differences between the two time points in each group were assessed using the Wilcoxon signed rank ***:Discrimination thresholds(color and chromatic-achromatic contrast vision)and their corresponding sensitivity,calculated as the inverse of the discrimination threshold,were *** of the data revealed higher contrast threshold results(i.e.,worse contrast sensitivity)in the COVID-19 group than in the control group for all spatial frequencies studied in the Optopad-CSF achromatic test and most of the spatial frequencies studied in the Optopad-CSF chromatic test for the red-green and blue-yellow *** addition,color threshold results in the COVID-19 group were also significantly higher(i.e.,worse color sensitivity)for almost all color mechanisms studied in the Optopad-Color *** 6mo,most of the differences found between the groups were maintained despite COVID-19 ***:The present results provide preliminary evidence that visual perception may be impaired in COVID-19

关键词： SARS-CoV-2 COVID-19 visual perception contrast sensitivity function color vision

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