Final results from the Betaseron (interferon β-1b) Pregnancy Registry: a prospective observational study of birth defects and pregnancy-related adverse events

ObjectiveWomen with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon β-1b (IFNβ-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population.DesignFrom 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit.SettingPatients in the USA who met these criteria were enrolled in the registry.ResultsThe registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNβ-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit.ConclusionsThe small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNβ-1b.Clinical trials registration numberNCT00317564

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina

Fil: Libster, Romina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Coviello, Silvina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Hijano, Diego R. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Dunaiewsky, Mariana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Reynoso, Natalia. Hospital Municipal Materno Infantil de San Isidro; Argentina.Fil: Cavalieri, Maria L. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Guglielmo, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Areso, M. Soledad. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Gilligan, Tomas. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santucho, Fernanda. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Gregorio, Gabriela L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Moreno, Rina. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Lutz, Maria I. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Panigasi, Alicia L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Saligari, Liliana. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Caballero, Mauricio T. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Egües Almeida, Rodrigo M. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Gutierrez Meyer, Maria E. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Neder, Maria D. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Davenport, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Del Valle, Maria P. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santidrian, Valeria S. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Mosca, Guillermina. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alvarez, Liliana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Landa, Patricia. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Pota, Ana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Boloñati, Norma. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Dalamon, Ricardo. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Sanchez Mercol, Victoria I. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Espinoza, Marco. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Peuchot, Juan Carlos. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Karolinski, Ariel. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bruno, Miriam. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Borsa, Ana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Ferrero, Fernando. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bonina, Angel. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Ramonet, Margarita. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Albano, Lidia C. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Luedicke, Nora. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alterman, Elias. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Savy, Vilma L. ANLIS Dr.C.G.Malbrán. Instituto de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Virosis Respiratoria; Argentina.Fil: Chappell, James D. Vanderbilt University. Pathology, Nashville, Tennessee; Estados Unidos.Fil: Edwards, Kathryn M. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Melendi, Guillermina A. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Polack, Fernando P. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Background: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. Methods: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. Results: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). Conclusions: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Acoustic tracking of a threatened juvenile shark species, the smooth hammerhead (Sphyrna zygaena), reveals vulnerability to exploitation at the boundary of a marine reserve

The coastal waters of South Africa are habitat to a diverse composition of sharks that are vulnerable to exploitation, many of which are endemic and/or classified by the International Union for Conservation of Nature (IUCN) Red List as Threatened or Data Deficient. Accordingly, this region has been identified as a global research and conservation priority for elasmobranchs. The De Hoop Marine Protected Area (MPA), in the Western Cape Province of South Africa, provides 288 km2 of no-take protection within its boundaries. However, the region experiences heavy commercial fishing, with two vessels actively operating as dedicated shark longliners (as of 2022). When crossing MPA boundaries, sharks are susceptible to capture by these vessels. Utilizing passive acoustic telemetry, the present study evaluated the movements of a threatened juvenile shark species, the smooth hammerhead (Sphyrna zygaena), both inside and adjacent to the De Hoop MPA, and along the greater coastline. Movement data from 20 tagged sharks were used to explore the effects of spatial, environmental, and management variables on their residency and movement patterns. Results indicate a high reliance of sharks on unprotected waters immediately adjacent to the MPA’s eastern boundary, an area of high biological productivity due to its proximity to the mouth of an estuary. Although some tagged sharks did move regionally along the South African coastline, individuals spent 95% of their days detected just outside the eastern boundary of the MPA, rendering them vulnerable to commercial shark longlining occurring there. These findings have conservation implications for smooth hammerhead sharks in South Africa and present an opportunity to revisit management practices that may optimize spatial protection for an important life stage of this threatened species

Successful parks for sharks: No-take marine reserve provides conservation benefits to endemic and threatened sharks off South Africa

Sharks are among the most threatened vertebrates on the planet. Marine protected areas (MPAs) have been widely established and promoted as a shark conservation tool. However, the geographic ranges of most imperiled shark species (endemic and threatened) fall outside the current global networks of MPAs, leaving the protective benefits of this tool questionable for the shark species of highest conservation concern. The Western Cape of South Africa is a hotspot for endemic and threatened shark species. Here, we examined the potential protective benefit of a no-take marine reserve (the De Hoop MPA) for imperiled shark species using baited remote underwater video stations (BRUVS). Eleven shark species were documented, with six of 11 species (55%) classified as threatened with extinction by the International Union for the Conservation of Nature. The composition of the shark assemblage was dominated by small to mid-sized species, including small endemics. Species-specific habitat preferences were identified, with all these habitats represented in the MPA. Frequency of occurrence and relative abundance of sharks on BRUVS were significantly higher inside the De Hoop MPA than outside. Both protected and commercially exploited sharks species exhibited higher relative abundance inside the MPA. Relative abundance also increased inside the MPA with increasing distance from the reserve boundaries. Our findings suggest that no-take MPAs can be an effective tool for protecting shark species of conservation concern, including threatened endemics, particularly if the MPA adequately incorporates their preferred habitats

Immunogenicity of a Fap2 peptide mimotope of Fusobacterium nucleatum and its potential use in the diagnosis of colorectal cancer

Abstract Background The role of Fusobacterium nucleatum Fap2 protein in the development of colorectal cancer has recently been explained. Fap2, when bound to the human inhibitory receptor, TIGIT, inhibits the cytotoxic activity of natural killer (NK) cells against cancer cells, thus, allowing proliferation of the latter eventually leading to tumor growth. The aim of the study was to identify the immunogenicity of a peptide mimotope of the Fap2 protein and to determine the reactivity of colorectal cancer patients’ sera against the mimotope. Methods Immunogenic epitope of the Fap2 protein of F. nucleatum was selected using the B-cell epitope prediction of the Immune Epitope Database and Analysis Resource (IEDB). The immunogenicity of the synthetic peptide mimotope of the Fap2 protein was determined in animal models and reactivity of colorectal cancer patients’ sera against the mimotope was done by indirect ELISA. Results Results show that the selected peptide mimotope, with sequence TELAYKHYFGT, of the outer membrane protein Fap2 of F. nucleatum is immunogenic. Increase in the absorbance readings of peptide-immunized rabbit sera was observed starting Week 1 which was sustained up to Week 10 in the indirect ELISA performed. Colorectal cancer cases (n = 37) were all reactive in an ELISA-based analysis using the mimotope as the capture antigen. Conclusions In this study, we identified an immunogenic epitope of the Fap2 protein of the Fusobacterium nucleatum. We demonstrated the reactivity of serum of histopathologically confirmed CRC patients in a peptide-capture indirect ELISA which may serve as proof of concept for the development of CRC diagnostics