Preclinical Studies of NEAST (Neutralizing Equine Anti-Shiga Toxin): A Potential Treatment for Prevention of Stec-Hus

STEC-HUS is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia and acute kidney injury. Despite the magnitude of the social and economic problems caused by STEC infections, there are currently no specific therapeutic options on the market. HUS is a toxemic disorder and the therapeutic effect of the early intervention with anti-toxin neutralizing antibodies has been supported in several animal models. We have designed novel protein nanoparticles with very strong immunogenic capacity by inserting Stx1B and Stx2B subunits of Shiga toxin to Brucella abortus Lumazine Synthase (BLS). The chimeric BLS-StxBs particles elicited strong neutralizing antibodies against Shiga toxins in horses. Based on these responses, we produced NEAST (Neutralizing Equine Anti-Shiga Toxin), composed of purified F(ab’)2 fragments. In this report we present the preclinical analysis of this new treatment. As a general conclusion, NEAST shows a very strong neutralizing capacity against 8 Shiga toxin variants in preclinical models of STEC-HUS. NEAST is also able to neutralize pathologic effects after previous exposure to Shiga Toxin, defining a potential therapeutic window. Besides, NEAST shows an excellent pharmacokinetics and safety profile in animal models. Overall, these results indicate that NEAST is a very good drug candidate for preventing the onset of HUS in STEC-infected patients and validate the conduction of a first in human clinical study at the Hospital Italiano de Buenos Aires in order to evaluate its safety and pharmacokinetic profiles in healthy adult volunteers.Fil: Hiriart, Yanina. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Pardo, Romina Paola. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bukata, Lucas. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lauché, Constanza Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Muñoz, Luciana. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Berengeno, Andrea Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Colonna, Mariana. Inmunova S.A; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Goldbaum, Fernando Alberto. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Sanguineti, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina. Inmunova S.A; ArgentinaFil: Zylberman, Vanesa. Inmunova S.A; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentin

Ecological Momentary Assessment of Awake Bruxism Behaviors: A Scoping Review of Findings from Smartphone-Based Studies in Healthy Young Adults

Background: The recent introduction of ecological momentary assessment (EMA) smartphone-based strategies has allowed achieving some interesting data on the frequency of different awake bruxism (AB) behaviors reported by an individual in the natural environment. Objective: The present paper aims to review the literature on the reported frequency of AB based on data gathered via smartphone EMA technology. Methods: On September 2022, a systematic search in the Pubmed, Scopus and Google Scholar databases was performed to identify all peer-reviewed English-language studies assessing awake bruxism behaviors using a smartphone-based Ecological Momentary Assessment. The selected articles were assessed independently by two authors according to a structured reading of the articles’ format (PICO). Results: A literature search, for which the search terms “Awake Bruxism” and “Ecological Momentary Assessment” were used, identified 15 articles. Of them, eight fulfilled the inclusion criteria. The results of seven studies using the same smartphone-based app reported a frequency of AB behaviors in the range between 28.3 and 40% over one week, while another investigation adopted a different smartphone-based EMA approach via WhatsApp using a web-based survey program and reported an AB frequency of 58.6%. Most included studies were based on convenience samples with limited age range, highlighting the need for more studies on other population samples. Conclusions: Despite the methodological limits, the results of the reviewed studies provide a standpoint for comparison for future studies on the epidemiology of awake bruxism behaviors

Safety and effectiveness of RBD-specific polyclonal equine F(ab´)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: A retrospective cohort study

Background Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population. Methods We conducted a retrospective cohort study at “Hospital de Campaña Escuela-Hogar" (HCEH) in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. Findings Subsequent clinical records of 446 non-exposed (Controls) and 395 exposed (EPIC) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95% CI: 0.46–0.96) P = 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n = 379), OR 0.58 (95% CI 0.39 to 0.85) P = 0.005. Overall and serious adverse events were not significantly different between groups. Conclusions In this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.Fil: Farizano Salazar, Diego H.. Hospital de Campaña Escuela Hogar; ArgentinaFil: Achinelli, Fernando. Hospital de Campaña Escuela Hogar; ArgentinaFil: Colonna, Mariana. Inmunova; ArgentinaFil: Pérez, Lucía. Hospital Italiano; ArgentinaFil: Giménez, Analía A.. Hospital de Campaña Escuela Hogar; ArgentinaFil: Ojeda, Maria Alejandra. Hospital de Campaña Escuela Hogar; ArgentinaFil: Miranda Puente, Susana N.. Hospital de Campaña Escuela Hogar; ArgentinaFil: Sánchez Negrette, Lía. Hospital de Campaña Escuela Hogar; ArgentinaFil: Cañete, Florencia. Hospital de Campaña Escuela Hogar; ArgentinaFil: Martelotte Ibarra, Ornela I.. Hospital de Campaña Escuela Hogar; ArgentinaFil: Sanguineti, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Spatz, Linus. Inmunova; ArgentinaFil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Massa, Carolina. Inmunova; ArgentinaFil: Rivas, Marta. Inmunova; ArgentinaFil: Pichel, Mariana. Inmunova; ArgentinaFil: Hiriart, Yanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Zylberman, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gallego, Sandra Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Konigheim, Brenda Salome. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Fernández, Francisco. No especifíca;Fil: Deprati, Matías. No especifíca;Fil: Roubicek, Ian. Inmunova; ArgentinaFil: Giunta, Diego Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; ArgentinaFil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Lopardo, Gustavo. No especifíca;Fil: Belloso, Waldo Horacio. Hospital Italiano; Argentin

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial

Background: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. Methods: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). Findings: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65 1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5 28% [-3 95; 14 50]; p = 0 15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14 2 (§ 0 7) days in the INM005 group and 16 3 (§ 0 7) days in the placebo group, hazard ratio 1 31 (95% CI 1 0 to 1 74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6 9% the INM005 group and 11 4% in the placebo group (risk difference [95% IC]: 0 57 [0 24 to 1 37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.Fil: Lopardo, Gustavo. Municipalidad de Vicente Lopez (buenos Aires). Hospital Municipal Doctor Bernardo Houssay.; ArgentinaFil: Belloso, Waldo H.. Hospital Italiano; ArgentinaFil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Colonna, Mariana. Inmunova; ArgentinaFil: Sanguineti, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Inmunova; ArgentinaFil: Zylberman, Vanesa. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Muñoz, Luciana. Inmunova; ArgentinaFil: Dobarro, Martín. Sanatorio Sagrado Corazón; ArgentinaFil: Lebersztein, Gabriel. Sanatorio Sagrado Corazón; ArgentinaFil: Farina, Javier. Gobierno de la Provincia de Buenos Aires. Hospital de Alta Complejidad Cuenca Alta Doctor Nestor Carlos Kirchner.; ArgentinaFil: Vidiella, Gabriela. Sanatorio Agote. Dr. Luis Agote; ArgentinaFil: Bertetti, Anselmo. Sanatorio Guemes Sociedad Anonima.; ArgentinaFil: Crudo, Favio. Universidad Nacional de San Antonio de Areco; ArgentinaFil: Alzogaray, Maria Fernanda. Instituto Medico Platense.; ArgentinaFil: Barcelona, Laura. Municipalidad de Vicente Lopez (buenos Aires). Hospital Municipal Doctor Bernardo Houssay.; ArgentinaFil: Teijeiro, Ricardo. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Lambert, Sandra. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Scublinsky, Darío. Clinica Zabala.; ArgentinaFil: Iacono, Marisa. Provincia del Neuquen. Hospital Provincial Neuquen "dr. E. Castro Rendon"; ArgentinaFil: Stanek, Vanina. Hospital Italiano; ArgentinaFil: Solari, Rubén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Cruz, Pablo. No especifíca;Fil: Casas, Marcelo Martín. Clinica Adventista Belgrano; ArgentinaFil: Abusamra, Lorena. Hospital Municipal Dr. Diego Thompson; ArgentinaFil: Luciardi, Héctor Lucas. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hosp. Centro de Salud "zenon Santillan"; ArgentinaFil: Cremona, Alberto. Hospital Italiano de La Plata; ArgentinaFil: Caruso, Diego. Hospital Español; ArgentinaFil: de Miguel, Bernardo. No especifíca;Fil: Perez Lloret, Santiago. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Millán, Susana. No especifíca;Fil: Kilstein, Yael. No especifíca;Fil: Pereiro, Ana. Fundación Mundo Sano; ArgentinaFil: Sued, Omar. Fundación Huésped; ArgentinaFil: Cahn, Pedro. Fundación Huésped; ArgentinaFil: Spatz, Linus. Inmunova; ArgentinaFil: Goldbaum, Fernando Alberto. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de San Martin. Centro de Rediseño E Ingenieria de Proteinas.; Argentin

Desarrollo de un suero equino hiperinmune para el tratamiento de COVID-19 en Argentina

La enfermedad denominada COVID-19 es causada por el coronavirus SARS-CoV-2 y es actualmente considerada una pandemia a nivel global. El desarrollo de vacunas es sin duda la mejor estrategia a largo plazo, pero debido a la emergencia sanitaria, existe una necesidad urgente de encontrar soluciones rápidas y efectivas para el tratamiento de la enfermedad. Hasta la fecha, el uso de plasma de convalecientes es la única inmunoterapia disponible para pacientes hospitalizados con COVID-19. El uso de anticuerpos policlonales equinos (EpAbs) es otra alternativa terapéutica interesante. La nueva generación de EpAbs incluyen el procesamiento y purificación de los mismos y la obtención de fragmentos F(ab’)2 con alta pureza y un excelente perfil de seguridad en humanos. Los EpAbs son fáciles de producir, lo cual permite el desarrollo rápido y la elaboración a gran escala de un producto terapéutico. En este trabajo mostramos el desarrollo de un suero terapéutico obtenido luego de la inmunización de caballos utilizando el receptor-binding domain de la glicoproteína Spike del virus. Nuestro producto mostró ser alrededor de 50 veces más potente en ensayos de seroneutralización in vitro que el promedio de los plasmas de convalecientes. Estos resultados nos permitirían testear la seguridad y eficacia de nuestro producto en ensayos clínicos de fase 2/3 a realizarse a partir de julio de 2020 en la zona metropolitana de Buenos Aires, Argentina.The disease named COVID-19, caused by the SARS-CoV-2 coronavirus, is currently generating a global pandemic. Vaccine development is no doubt the best long-term immunological approach, but in the current epidemiologic and health emergency there is a need for rapid and effective solutions. Convalescent plasma is the only antibody-based therapy available for COVID-19 patients to date. Equine polyclonal antibodies (EpAbs) put forward a sound alternative. The new generation of processed and purified EpAbs containing highly purified F(ab’)2 fragments demonstrated to be safe and well tolerated. EpAbs are easy to manufacture allowing a fast development and scaling up for a treatment. Based on these ideas, we present a new therapeutic product obtained after immunization of horses with the receptor-binding domain of the viral Spike glycoprotein. Our product shows around 50 times more potency in in vitro seroneutralization assays than the average of convalescent plasma. This result may allow us to test the safety and efficacy of this product in a phase 2/3 clinical trial to be conducted in July 2020 in the metropolitan area of Buenos Aires, Argentina.Fil: Zylberman, Vanesa. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanguineti, Santiago. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pontoriero, Andrea. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Higa, Sandra V.. Instituto Biológico Argentino S.A.I.C.; ArgentinaFil: Cerutti, Maria Laura. Universidad Nacional de San Martín. Centro de Rediseño e Ingeniería de Proteínas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morrone Seijo, Susana María. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pardo, Romina Paola. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Muñoz, Luciana. Inmunova; ArgentinaFil: Acuña Intieri, María Eugenia. Universidad Nacional de San Martín. Centro de Rediseño e Ingeniería de Proteínas; ArgentinaFil: Alzogaray, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Avaro, Martín M.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Benedetti, Estefanía. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Bocanera, Laura. mAbxience; ArgentinaFil: Bukata, Lucas. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bustelo, Marina S.. Inmunova; ArgentinaFil: Campos, Ana M.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Colonna, Mariana. Inmunova; ArgentinaFil: Correa, Elisa. mAbxience; ArgentinaFil: Cragnaz, Lucí­a. mAbxience; ArgentinaFil: Dattero, María E.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Dellafiore, María Andrea. mAbxience; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Foscaldi, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: González, Joaquí­n V.. Inmunova; ArgentinaFil: Guerra, Luciano Lucas. mAbxience; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Labanda, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Lauché, Constanza Elena. Inmunova; ArgentinaFil: López, Juan C.. Instituto Biológico Argentino S.A.I.C.; ArgentinaFil: Martínez, Anabela M.. Instituto Biológico Argentino S.A.I.C.; ArgentinaFil: Otero, Lisandro Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Peyric, Elías H.. Instituto Biológico Argentino S.A.I.C.; ArgentinaFil: Ponziani, Pablo F.. Instituto Biológico Argentino S.A.I.C.; ArgentinaFil: Ramondino, Romina. Inmunova; ArgentinaFil: Rinaldi, Jimena Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rodrí­guez, Santiago. mAbxience; ArgentinaFil: Russo, Javier E.. Instituto Biológico Argentino S.A.I.C.; ArgentinaFil: Russo, Mara Laura. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saavedra, Soledad Lorena. Instituto Biológico Argentino S.A.I.C.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seigelchifer, Mauricio. mAbxience; ArgentinaFil: Sosa, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Vilariño, Claudio. Universidad Nacional de San Martín. Centro de Rediseño e Ingeniería de Proteínas; ArgentinaFil: López Biscayart, Patricia. Instituto Biológico Argentino S.A.I.C.; ArgentinaFil: Corley, Esteban. mAbxience; ArgentinaFil: Spatz, Linus. Inmunova; ArgentinaFil: Baumeister, Elsa. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Goldbaum, Fernando Alberto. Universidad Nacional de San Martín. Centro de Rediseño e Ingeniería de Proteínas; Argentina. Inmunova; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Ecological Momentary Assessment of Awake Bruxism Frequency in Patients with Different Temporomandibular Disorders

Self-reported awake bruxism (AB) has been associated with temporomandibular disorders (TMD). However, the daily amount of AB behavior has not been quantified in pain patients. Therefore, this study aimed to assess AB frequency in patients with myofascial pain and temporomandibular joint (TMJ) pain and compare it to a group of pain-free individuals. Eighty-four individuals belonging to either a TMD group (n = 54) or a healthy control group (n = 30) were selected. AB frequency was obtained by ecological momentary assessment with a dedicated smartphone application that sent sound alerts at random intervals during the day for one week. Upon receiving the alert, the volunteer reported the current muscular condition and/or the teeth position, i.e., relaxed jaw muscle, jaw bracing, teeth contact, teeth clenching, or teeth grinding. Data were evaluated by independent t-test (α = 0.05). During the seven days, AB frequency was 62.1% ± 26.8% for TMD patients and 36.2% ± 27.3% for pain-free subjects (p p < 0.001), while teeth contact, clenching, and grinding did not differ between groups. Moreover, no differences were found in AB frequency between myofascial pain and TMJ pain patients. Therefore, TMD patients have higher AB frequency characterized by jaw bracing, irrespective of pain location

Development of a product anti-Shiga toxin for prevention of the hemolytic uremic syndrome

The typical hemolytic uremic syndrome (HUS) is an orphan disease caused by Shiga toxin(Stx) producing Escherichia coli strains and characterized by acute kidney damage, microangiopathic hemolytic anemia and low platelet count. It is endemic in Argentina, the country with the highest incidence of HUS in the world. Stx is essential for its development and therefore, HUS is considered a toxemic non-bacteremic disorder, which could be treated with antibodies. Herein we describe the development of a new treatment capable of neutralizing the toxic effect of Stx and its variants. The treatment consists of F(ab')2 fragments from an equine antiserum whose efficacy and potency against Stx1 and Stx2 were proved in different preclinical models. The product was shown to be safe in animals. Furthermore, the anti-Stx F(ab')2 pharmacokinetic was shown to be similar to that of analogous compounds and a therapeutic window for its administration was determined. Altogether, these preclinical results warrant testing in humans. The phase I clinical trial will be performed at the Hospital Italiano in Buenos Aires to evaluate the safety and pharmacokinetics of the product in healthy adult volunteers. Based on the results of this study, a phase II clinical trial will be planned in pediatric patients diagnosed with infection by Stx-producing E. coli strains

β-adrenergic stimulation controls the expression of a thioesterase specific for very-long-chain fatty acids in perfused hearts

Arachidonic acid is not freely stored in the cells. A number of different pathways for the mobilization of this compound have been proposed, including a novel mechanism that involves the release of arachidonic acid from arachidonoyl-CoA by a thioesterase with substrate specificity for very-long-chain fatty acids. In rat heart, the acyl-CoA thioesterase activity can be regulated by a mechanism that involves β-adrenoceptors. In this paper we demonstrate that β-adrenergic agonists also regulate the acyl-CoA thioesterase mRNA levels. Isoproterenol (10-7) a concentration known to exert physiological responses - increases in a time-dependent manner the acyl-CoA thioesterase mRNA levels, an effect blocked by a specific β-adrenoceptor antagonist. In addition, our results show that cAMP is involved in this process. The acyl-CoA thioesterase mRNA levels are also increased by fasting, but not by di(2-ethylhexyl)phthalate, a peroxisome proliferator. These results may suggest the existence of a β-adrenoceptor-activated regulatory pathway for arachidonic acid release in cardiac tissue. © 2002 Elsevier Science (USA). All rights reserved.Fil: Neuman, Maria Isabel. Universidad de Buenos Aires; ArgentinaFil: Maloberti, Paula Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Lisdero, Constanza. Universidad de Buenos Aires; ArgentinaFil: Colonna, Cecilia. Universidad de Buenos Aires; ArgentinaFil: Peralta, Jorge. Universidad de Buenos Aires; ArgentinaFil: Poderoso, Juan José. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Podestá, Ernesto J.. Universidad de Buenos Aires; Argentin

Expression of Nitric Oxide Synthases in Rat Adrenal Zona Fasciculata Cells

Nitric oxide (NO) synthase (NOS) expression was analyzed in rat adrenal zona fasciculata. Both neuronal NOS and endothelial NOS mRNAs were detected by RT-PCR, immunohistochemistry, and immunoblot analysis. The biochemical characterization of adrenal zona fasciculata NOS enzymatic activity confirmed the presence of a constitutive isoform. In a cell line derived from mouse adrenal cortex, only endothelial NOS expression was detected by both RT-PCR and immunoblot analysis. Nitrate plus nitrite levels in Y1 cell incubation medium were increased in the presence of L-arginine and the calcium ionophore A23187, but not D-arginine, indicating enzymatic activity. Moreover, a low, but significant, conversion of Larginine to L-citrulline, abolished by the NOS inhibitor, N(G)-nitro-L-arginine, was detected in Y1 cells. The effect of L-arginine on pregnenolone production was examined. L-Arginine decreased both basal and ACTH-stimulated pregnenolone production in Y1 cells. The inhibitory effect of L-arginine could be attributed to endogenously generated NO, because it was blocked by N(G)-nitro-L-arginine, and it was mimicked by the addition of a NO donor, diethylenetriamine-NO. An inhibitory effect of NO on pregnenolone production from 22Rhydroxycholesterol and on steroidogenic acute regulatory protein expression was also determined. Taken together, these results suggest that at least part of the adrenal NO could derive from steroidogenic cells and modulate their function.Fil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Lotito, Sebastian. Universidad de Buenos Aires, Facultad de Medicina,Departamento de Bioquimica Humana; ArgentinaFil: Colonna, Cecilia. Universidad de Buenos Aires, Facultad de Medicina,Departamento de Bioquímica Humana; ArgentinaFil: Finkielstein, Carla. Universidad de Buenos Aires.Facultad de Medicina.Departamento de Bioquímica Humana; ArgentinaFil: Pomeraniec, Yael. Universidad de Buenos Aires; ArgentinaFil: Grión, Natalia. Universidad de Buenos Aires; ArgentinaFil: Gadda, Luciana. Universidad de Buenos Aires; ArgentinaFil: Maloberti, Paula Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin