Search

Background We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1–2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly in older adults, and higher than expected reactogenicity after the second vaccination were observed. In the current study, we evaluated the safety and immunogenicity of an optimised formulation of CoV2 preS dTM adjuvanted with AS03 to inform progression to phase 3 clinical trial. Methods This phase 2, randomised, parallel-group, dose-ranging study was done in adults (≥18 years old), including those with pre-existing medical conditions, those who were immunocompromised (except those with recent organ transplant or chemotherapy) and those with a potentially increased risk for severe COVID-19, at 20 clinical research centres in the USA and Honduras. Women who were pregnant or lactating or, for those of childbearing potential, not using an effective method of contraception or abstinence, and those who had received a COVID-19 vaccine, were excluded. Participants were randomly assigned (1:1:1) using an interactive response technology system, with stratification by age (18–59 years and ≥60 years), rapid serodiagnostic test result (positive or negative), and high-risk medical conditions (yes or no), to receive two injections (day 1 and day 22) of 5 7mu;g (low dose), 10 7mu;g (medium dose), or 15 7mu;g (high dose) CoV2 preS dTM antigen with fixed AS03 content. All participants and outcome assessors were masked to group assignment; unmasked study staff involved in vaccine preparation were not involved in safety outcome assessments. All laboratory staff performing the assays were masked to treatment. The primary safety objective was to describe the safety profile in all participants, for each candidate vaccine formulation. Safety endpoints were evaluated for all randomised participants who received at least one dose of the study vaccine (safety analysis set), and are presented here for the interim study period (up to day 43). The primary immunogenicity objective was to describe the neutralising antibody titres to the D614G variant 14 days after the second vaccination (day 36) in participants who were SARS-CoV-2 naive who received both injections, provided samples at day 1 and day 36, did not have protocol deviations, and did not receive an authorised COVID-19 vaccine before day 36. Neutralising antibodies were measured using a pseudovirus neutralisation assay and are presented here up to 14 days after the second dose. As a secondary immunogenicity objective, we assessed neutralising antibodies in non-naive participants. This trial is registered with ClinicalTrials.gov (NCT04762680) and is closed to new participants for the cohort reported here. Findings Of 722 participants enrolled and randomly assigned between Feb 24, 2021, and March 8, 2021, 721 received at least one injection (low dose=240, medium dose=239, and high dose=242). The proportion of participants reporting at least one solicited adverse reaction (injection site or systemic) in the first 7 days after any vaccination was similar between treatment groups (217 [91%] of 238 in the low-dose group, 213 [90%] of 237 in the medium-dose group, and 218 [91%] of 239 in the high-dose group); these adverse reactions were transient, were mostly mild to moderate in intensity, and occurred at a higher frequency and intensity after the second vaccination. Four participants reported immediate unsolicited adverse events; two (one each in the low-dose group and medium-dose group) were considered by the investigators to be vaccine related and two (one each in the low-dose and high-dose groups) were considered unrelated. Five participants reported seven vaccine-related medically attended adverse events (two in the low-dose group, one in the medium-dose group, and four in the high-dose group). No vaccine-related serious adverse events and no adverse events of special interest were reported. Among participants naive to SARS-CoV-2 at day 36, 158 (98%) of 162 in the low-dose group, 166 (99%) of 168 in the medium-dose group, and 163 (98%) of 166 in the high-dose group had at least a two-fold increase in neutralising antibody titres to the D614G variant from baseline. Neutralising antibody geometric mean titres (GMTs) at day 36 for participants who were naive were 2189 (95% CI 1744–2746) for the low-dose group, 2269 (1792–2873) for the medium-dose group, and 2895 (2294–3654) for the high-dose group. GMT ratios (day 36: day 1) were 107 (95% CI 85–135) in the low-dose group, 110 (87–140) in the medium-dose group, and 141 (111–179) in the high-dose group. Neutralising antibody titres in non-naive adults 21 days after one injection tended to be higher than titres after two injections in adults who were naive, with GMTs 21 days after one injection for participants who were non-naive being 3143 (95% CI 836–11 815) in the low-dose group, 2338 (593–9226) in the medium-dose group, and 7069 (1361–36 725) in the high-dose group. Interpretation Two injections of CoV2 preS dTM-AS03 showed acceptable safety and reactogenicity, and robust immunogenicity in adults who were SARS-CoV-2 naive and non-naive. These results supported progression to phase 3 evaluation of the 10 7mu;g antigen dose for primary vaccination and a 5 7mu;g antigen dose for booster vaccination. Funding Sanofi Pasteur and Biomedical Advanced Research and Development Authority.

Introduction Adoption of control tools for atopic dermatitis (AD) in Latin America (LA) is currently very limited. Clinical assessment tools represent a practical method to measure the impact of treatment on disease activity and on the quality of life of patients. However, the use of these tools in the LA clinical practice setting is limited. Methods A selected panel of Latin American experts in fields related to atopic dermatitis were provided with a series of relevant questions to address prior to the multi-day conference. Within this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion, until a consensus was achieved. Results The panel proposes specific and realistic recommendations for implementing control tools for AD care in LA. In creating these recommendations, the authors strove to address all barriers to the widespread use of these tools. Conclusion This article includes a narrative analysis of barriers to AD control in LA and provides necessary recommendations to integrate and increase the use of validated AD control assessment tools throughout the region.

ObjectiveThe French Polynesia Zika virus (ZIKV) outbreak (2013–2014) broadened the known manifestations of ZIKV disease (ZVD) to include neural and congenital syndromes. A subsequent epidemic in the Americas (2015–2016) caused >685,000 suspected/confirmed cases before seemingly disappearing as fast as it expanded. A study was implemented (2017–2018) to detect ZVD cases in the region (Mexico, Honduras, Colombia and Puerto Rico), with the aim of validating surveillance methodology so as to increase sensitivity in case detection, which would have potential application for future vaccine development endeavors.Study design and settingTo identify potential cases, we focused on signs/symptoms that were frequently associated with ZVD for confirmation by PCR. Serostatus and seroconversion were evaluated by ZIKV non-structural protein 1 blockade-of-binding enzyme-linked immunosorbent assay (BOB ELISA) and microneutralization assay.ResultsOverall, 2,400 participants aged 15–40 years were enrolled; 959 (40.0%) had signs/symptoms that could be associated with ZVD: axillary temperature ≥37°C (64.3%), myalgia (60.8%) and arthralgia (58.6%). Three suspected cases were virologically confirmed. Zika seroprevalence was high at study initiation (52.6% [BOB ELISA] and 56.0% [microneutralization assay]). In participants who were Zika seronegative, low seroconversion rates were observed after one year follow-up (3.6% [BOB ELISA] and 3.1% [microneutralization assay]).ConclusionThe ZIKV continued to circulate in the Americas at very low levels following the 2015–2016 outbreak. The epidemiological factors driving Zika’s rapid rise and decline remain poorly understood.Clinical trial registrationClinicaltrials.gov: NCT03158233 BARDA (Contract # HHSO100201600039C) WHO Universal Trial Number: U1111-1183-5687.

Summary Background In the absence of a licensed vaccine, Clostridioides (formerly Clostridium) difficile infection represents a substantial health burden. The aim of this study was to evaluate the efficacy, immunogenicity, and safety of a toxoid vaccine candidate. Methods We did a phase 3 multicentre, observer-blind, randomised, controlled trial at 326 hospitals, clinics, and clinical research centres in 27 countries in the USA, Canada, Latin America, Europe, and the Asia-Pacific region. We included adults aged 50 years or older who were considered to be at an increased risk of C difficile infection because they had previously had two hospital stays (each ≥24 h in duration) and had received systemic antibiotics in the previous 12 months (risk stratum 1), or because they were anticipating being admitted to hospital for 72 h or more for elective surgery within 60 days of enrolment (risk stratum 2). Eligible participants were stratified by geographical region and the two risk strata, and randomly assigned (2:1), with a fixed block size of three, to receive either a C difficile toxoid vaccine candidate, containing toxoids A and B (C difficile vaccine candidate group), or a placebo vaccine (placebo group). Participants, investigators, and personnel responsible for collecting safety data and analysing blood and stool samples were masked to group assignment. Personnel responsible for study product preparation and administration were not masked to group assignment. One dose (0·5 mL) of C difficile vaccine candidate or placebo vaccine was administered intramuscularly on days 0, 7, and 30. The primary outcome was the efficacy of the vaccine in preventing symptomatic C difficile infection, defined as having three or more loose stools in a period of 24 h or less, loose stools for 24 h or more, and a PCR-positive test for C difficile toxin B in a loose stool sample, within 3 years after the final vaccine dose. The primary outcome was measured in the modified intention-to-treat population (ie, all participants who received at least one injection of the assigned vaccine). The safety of the vaccine was assessed in the safety analysis set (ie, all participants who had received at least one injection, analysed according to the product received). This study is registered with WHO/ICTRP, number U111-1127-7162, and ClinicalTrials.gov , number NCT01887912 , and has been terminated. Findings Between July 30, 2013, and Nov 17, 2017, we enrolled and randomly assigned 9302 participants to the C difficile vaccine candidate group (n=6201) or to the placebo group (n=3101). 6173 (99·5%) participants in the C difficile vaccine candidate group and 3085 (99·5%) participants in the placebo group received at least one dose of the vaccine. The study was terminated after the first planned interim analysis because of futility. In the C difficile vaccine candidate group, 34 C difficile infections were reported over 11 697·2 person-years at risk (0·29 infections per 100 person-years [95% CI 0·20–0·41]) compared with 16 C difficile infections over 5789·4 person-years at risk in the placebo group (0·28 infections per 100 person-years [0·16–0·45]), indicating a vaccine efficacy of −5·2% (95% CI −104·1 to 43·5). In the C difficile vaccine candidate group, 2847 (46·6%) of 6113 participants reported an adverse event within 30 days of injection compared with 1282 (41·9%) of 3057 participants in the placebo group. The proportion of participants who had an adverse event leading to study discontinuation was 4·8% in both groups (296 participants in the C difficile vaccine candidate group and 146 participants in the placebo group). 1662 (27·2%) participants in the C difficile vaccine candidate group reported at least one serious adverse event compared with 851 (27·8%) participants in the placebo group. Interpretation In adults at risk for C difficile infection, a bivalent C difficile toxoid vaccine did not prevent C difficile infection. Since the C difficile vaccine candidate met the criteria for futility, the study was terminated and clinical development of this vaccine candidate was stopped. Funding Sanofi Pasteur.

Talking about innovation and entrepreneurship, although it may seem similar, it is not. However, both concepts should always go hand in hand when undertaking any business idea and even more so, those that seek to empower entrepreneurs, in addition to seeking to strengthen the economic sectors of their region. The general objective of the research is to analyze the technological innovations in the textile sector in the canton of Esmeraldas-Ecuador, seeking to know the perception of the people with respect to this particular topic and its inclusion in this new modern era that is currently being lived, which is totally surrounded by technology. The population selected with the people who belong to the textile sector of the canton mentioned above, having a sample of 10 people to whom a semi-structured interview was applied, consisting of five (5) items that are related to the objective of the research, finally the technique and tool used for the processing and analysis of data is the software program Atlas. Ti software, which allows storing and recording the opinions obtained from the sample.

SummaryBackgroundThis study evaluated the safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein candidate vaccine, CoV2 preS dTM.MethodsThis Phase 2, modified double-blind, parallel-group study (NCT04762680) was conducted in adults, including those at increased risk of severe COVID-19. Participants were randomised 1:1:1, stratified by age (18–59/≥60 years), rapid serodiagnostic test (positive/negative) and high-risk medical conditions (yes/no), to receive two injections (day [D]1 and D22) of 5μg, 10μg or 15μg of CoV2 preS dTM antigen with fixed AS03 content. Interim safety and reactogenicity results (to D43) and neutralising antibodies (NAbs) against the D614G variant are presented (primary objectives).FindingsOf 722 participants enrolled and randomised between 24 February and 8 March 2021, 721 received ≥1 injections (5μg, n=240; 10μg, n=239; 15μg, n=242). Four participants reported unsolicited immediate adverse events (AEs), two were vaccine-related (investigator assessment). Five participants reported seven vaccine-related medically-attended AEs. No vaccine-related serious AEs and no AEs of special interest were reported. Solicited reactions (local and systemic) were reported at similar frequencies between study groups; these were mostly mild to moderate and transient, with higher frequency and intensity post-injection 2 than post-injection 1. In SARS-CoV-2 naïve participants at D36, 96·9%, 97.0% and 97·6% of participants had ≥4-fold-rise in NAb titres from baseline in the 5μg-, 10μg- and 15μg-dose groups, respectively. NAb titres increased with antigen dose in younger (GMTs: 2954, 3951 and 5142 for 5μg-, 10μg- and 15μg-dose groups) but not older adults (GMTs: 1628, 1393 and 1736, respectively). NAb titres in non-naïve adults after one injection were higher than titres after two injections in naïve adults.InterpretationTwo injections of CoV2 preS dTM-AS03 demonstrated acceptable safety and reactogenicity, and robust immunogenicity in SARS-CoV-2 naïve and non-naïve adults. These results informed antigen dose selection for progression to Phase 3 evaluation of primary and booster vaccination.

Annual vaccination is the most effective way to prevent seasonal influenza. Influenza vaccines in multi-dose vial (MDV) formats can facilitate timely vaccination of large populations by reducing per-dose costs and cold storage requirements compared to single-dose pre-filled syringe (PFS) formats. MDV vaccines require thiomersal or another preservative to prevent microbial contamination. We conducted a randomized, open-label trial in 302 healthy subjects aged 6 months to 17 years to evaluate the immunogenicity and safety of a quadrivalent influenza vaccine (QIV) in a thiomersal-containing MDV format compared to the licensed thiomersal-free PFS format. Subjects were randomly assigned in a 1:1 ratio to receive the MDV (n = 153) or PFS (n = 149) format. Post-vaccination hemagglutination inhibition titers for all four vaccine strains were ≥4.9-fold higher than baseline titers with no difference in magnitude between the MDV and PFS groups. Seroconversion rates per strain were also comparable between the two groups. There were no differences in reactogenicity or safety between the two vaccine formats. These results showed that the MDV format of QIV was as safe and immunogenic as the PFS format in infants, children, and adolescents. These findings support the use of MDV QIV as a resource-saving alternative for seasonal influenza vaccination.

Cervical cancer (CC) is one of the leading causes of cancer-associated mortalities in women from developing countries. Similar to other types of cancer, CC is considered to be a multifactorial disease, involving socioeconomic, cultural, immunological and epigenetic factors, as well as persistent human papilloma virus (HPV) infection. It has been well established that cancer stem cells (CSCs) play an important role in defining tumor size, the speed of development and the level of regression following treatment; therefore, CSCs are associated with a poor prognosis. CSCs have been detected in many types of cancer, including leukemia, pancreatic, colon, esophagus, liver, prostate, breast, gastric and lung cancer. In cervical cancer, CSCs have been associated with resistance to normally used drugs such as cisplatin. The present review summarizes the strategies that high-risk HPV viruses (HPV-16 and HPV-18) have developed to transform normal epithelial cells into cancer cells, as well as the cellular pathways and studies associated with the identification of cervical cancer stem cell biomarkers. In this sense, the present review provides state of the art information regarding CC development.

RESUMEN Objetivo: evaluar el grado de concordancia entre el modelo de evaluación del estado nutricional materna propuesto por Rosso-Mardones con el propuesto por Atalah Materiales y métodos: estudio de concordancia diagnóstica. Se incluyeron gestantes entre los 19 y 37 años, con una edad gestacional de 10 o más semanas; se excluyeron gestantes con: diabetes, enfermedad tiroidea, hipertensión asociada al embarazo, embarazos gemelares, malformaciones fetales graves, muerte fetal e hidrops fetalis. Muestreo no probabilístico. Se midieron las variables sociodemográficas, obstétricas y el estado nutricional. Se calculó el valor de kappa de concordancia entre las dos escalas de evaluación nutricional. Conclusiones: las escalas de evaluación nutricional en gestantes, nomograma de Rosso-Mardones y de Atalah, tienen un acuerdo considerable. Se requieren más estudios que evalúen la concordancia entre estas escalas en población gestante. ABSTRACT Objective: To assess the degree of agreement between the model for maternal nutritional assessment proposed by Rosso-Mardones and the one proposed by Atalah. Materials and methods: Diagnostic agreement study. Pregnant women between the ages of 19 and 37 years with a gestational age of 10 or more weeks were included; patients with diabetes, thyroid disease, pregnancy-associated hypertension, twin pregnancy, severe fetal malformation, fetal death and hydrops fetalis were excluded. Non-probabilistic sampling. Sociodemographic, obstetrical and nutritional status variables were measured. Results: Overall, 98 pregnant women were included. With the use of the Rosso-Mardones scale, 33% of the patients were classified as having a normal nutritional status, 22% as low weight, and 44% as overweight or obese. With the Atalah scale, 41% of the women were classified as having a normal nutritional status, 10% as low weight and 48% as overweight or obese. The weighted kappa value was 0.74 with a standard error of 0.04, a 95% CI of 0.66-0.82 and a p value < 0.05. Conclusions: There is substantial agreement between nutritional assessment scales used in pregnancy, namely the Rosso-Mardones nomogram and the Atalah scale. Further studies to assess the agreement of these scales in the pregnant population are required.

Las fuentes de informacion, su calidad y disponibilidad son esenciales para el desarrollo de los procesos de investigacion. Al abordar el tema de la frontera y su influencia en conformacion de la localidad de Cardenas en Rivas, Nicaragua se hace uso obligatorio de las fuentes de informacion disponibles para el enriquecimiento de los aspectos teoricos de la investigacion, los que se complementan y fundamentan con los datos recopilados en campo. Este articulo realiza un analisis de las fuentes encontradas que ayudan a sustentar los aspectos teoricos relacionados con esta localidad nicaraguense y que por su naturaleza fronteriza esta rodeada de aspectos relevantes que valen la pena rescatar. Este articulo escrito nace como parte de la investigacion doctoral titulada: Influencia de la frontera en la dinamica del proceso de conformacion local de Cardenas, en la region historica de Rivas , Nicaragua del programa de doctorado en Historia con mencion en estudios regionales y locales transdisciplinarios de la UNAN-Managua.

The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated.This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed.Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study.Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.

La contaminación del aire de interiores y de exteriores ha sido considerada un serio problema de salud pública a nivel mundial, el cual se asocia anualmente con alrededor de 7 millones de muertes (4.8 millones asociadas con el aire de exteriores y 2.2 millones con el aire de interiores). Entre las principales razones ligadas a estas muertes se encuentran: enfermedad pulmonar obstructiva crónica, neumonía, cardiopatía isquémica y cáncer de pulmón. Además, estudios epidemiológicos han asociado la exposición a este tipo de contaminantes con mayor susceptibilidad para la aparición de enfermedades infecciosas y no infecciosas. Entre las enfermedades infecciosas, una de las más importantes es la tuberculosis, la cual, durante el transcurso de los años, ha empeorado con el surgimiento de cepas resistentes a múltiples fármacos, así como por la asociación con otras afecciones como la diabetes mellitus tipo 2 y el síndrome de inmunodeficiencia adquirida (sida). A pesar del esfuerzo realizado por la Organización Mundial de la Salud (OMS) por detener esta epidemia, aún existen anualmente un gran número de muertes causadas por esta enfermedad: alrededor de 1.7 millones a nivel mundial. En esta revisión se hará un breve resumen de los efectos que tiene la exposición a la contaminación del aire de interiores y de exteriores en la respuesta inmune innata en contra de la tuberculosis, y cómo estas alteraciones pueden estar ligadas a la aparición de tuberculosis pulmonar. Indoor and outdoor air pollution has been considered a serious public health problem worldwide, and is associated annually with around 7 million deaths (4.8 million associated with outdoor air and 2.2 million indoor air). The main reasons for these deaths include: chronic obstructive pulmonary diseases, pneumonia, ischemic cardiopathy and lung cancer. In addition, epidemiological studies have associated exposure to this type of pollutants with a greater susceptibility to the development of infectious and non-infectious diseases. One of the most important infectious diseases is tuberculosis, which over the years has worsened with the emergence of resistant multi-drug strains, as well as with association with other diseases such as diabetes mellitus type 2 and the acquired immune deficiency syndrome (AIDS). In fact, despite efforts made by the World Health Organization to stop the epidemic, a large number of deaths (about 1.7 million worldwide) are still caused by this disease. In this review, a brief summary will be made of the effects of exposure to indoor and outdoor air pollution on the innate immune response against tuberculosis, and how these alterations could be linked to the development of pulmonary tuberculosis.

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3–8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3–8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

El estudio de las fronteras ha tenido un gran auge especialmente en los últimos años a nivel de Latinoamérica y el Caribe. Para el caso de Centroamérica, las fronteras han sido consideradas como zonas de conflicto entre los países que las comparten. Históricamente éstas no han tenido atención desde el Estado, permaneciendo olvidadas y atendidas solamente cuando aparecen nuevos conflictos limítrofes o territoriales. En otros diversos campos de las ciencias sociales y humanas, la noción de frontera es tomada en cuenta en un sentido más amplio y no se traduce sistemáticamente en los límites entre Estados. El término es utilizado para expresar una separación entre grupos culturales (frontera lingüística, religiosa) y se asocia a un contacto confuso, impreciso, móvil. La frontera tiene la capacidad de incidir de manera directa en la configuración de las localidades, ciudades y pueblos que se desarrollan a lo largo de ésta. Sin embargo, esta capacidad de influencia es divergente y discontinua por diversos factores de carácter histórico, geográfico, socioeconómico y político. La actual investigación tiene el propósito de producir una obra que aborde el estudio de la localidad de Cárdenas y de sus comarcas fronterizas, entendiéndolas como aquellos espacios de trascendencia para el desarrollo de éstas y de Nicaragua, desde una perspectiva integradora y multidisciplinaria.

A prospective study was conducted in four tertiary hospitals in Argentina and Mexico in order to describe the occurrence of Clostridium difficile infection (CDI) in these settings. The objective was to evaluate the incidence of CDI in at-risk populations in Argentina (one center) and Mexico (three centers) and to further explore potential study sites for vaccine development in this region. A prospective, descriptive, CDI surveillance study was conducted among hospitalized patients aged ≥40 years who had received ≥48 h of antibiotic treatment. Stool samples were collected from those with diarrhea within 30 days after starting antibiotics and analyzed for toxins A and B by ELISA, and positive samples were further tested by toxinogenic culture and restriction endonuclease analysis type assay. Overall, 466 patients were enrolled (193 in Argentina and 273 in Mexico) of whom 414 completed the follow-up. Of these, 15/414 (3.6%) experienced CDI episodes occurring on average 18.1 days after admission to hospital and 15.9 days after the end of antibiotics treatment. The incidence rate of CDI was 3.1 (95% CI 1.7–5.2) per 1000 patient-days during hospitalization, and 1.1 (95% CI 0.6–1.8) per 1000 patient-days during the 30-day follow-up period. This study highlighted the need for further evaluation of the burden of CDI in both countries, including the cases occurring after discharge from hospital. Keywords: Clostridium infections, Epidemiology, Latin America, Incidence

Background In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. Methods In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. Results A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. Conclusions The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.)

To prepare for a Phase III dengue vaccine efficacy trial, 20 investigational sites were selected for this observational study to identify dengue infections in a closed cohort (N = 3,000 children 9-16 years of age). Of 255 acute febrile episodes experienced by 235 children, 50 (21.3%) were considered serologically probable dengue, and 18 (7.7%) were considered virologically confirmed (i.e., dengue NS1 antigen positive) dengue cases. Considering the disease-free and at-risk period from study start to onset of symptoms, the overall incidence density of acute febrile episodes was 17.7 per 100 person-years of follow-up, ranging from 15.3 in Colombia to 22.0 in Puerto Rico. This study showed that all sites were capable of capturing and following up acute febrile episodes within a specific timeframe among the established cohort and to detect dengue cases.

The dengue virus is a member of the Flavivirus (FV) genus, which also includes the yellow fever virus. Dengue disease is caused by any 1 of 4 dengue virus serotypes and is a serious public health concern in Latin America. This study evaluated the safety and immunogenicity of a candidate recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in 9-16 year olds in Latin America.In this randomized, blinded, controlled study, volunteers received either 3 doses of CYD-TDV (n = 401) or placebo as first and second injection and tetanus/diphtheria/acellular pertussis vaccine as third injection (n = 199) at 0, 6 and 12 months. Adverse events were documented. Plaque reduction neutralization test antibody titers against the 4 CYD-TDV parental strains were measured before and 28 days after each dose. Seropositivity was defined as antibody titers ≥10 1/dil.The number of adverse reactions decreased after each successive CYD-TDV dose. After each CYD-TDV dose, antibody titers against all 4 serotypes were higher than baseline and respective predose titers. After the third dose of CYD-TDV, 100%, 98.6% and 93.4% of participants were seropositive for at least 2, at least 3 or all 4 serotypes, respectively. Higher antibody titers were observed in participants in the CYD-TDV group who were FV-seropositive at baseline compared with those who were FV-seronegative.CYD-TDV had a favorable safety profile and elicited antibody responses against all 4 dengue virus serotypes in 9-16 year olds in Latin America. These findings support the continued development of CYD-TDV.

RESUMENSe presenta una revisión sobre síndrome HELLP con mayor énfasis a las nuevas teorías que pretenden explicar la fisiopatología y unas recomendaciones para su manejo. El síndrome se caracteriza por daño endotelial microvascular. Sin embargo, la fisiopatología del síndrome aún no está bien definida. Existe un creciente interés en las citoquinas inflamatorias, factores genéticos y ambientales en la patogénesis de la misma. Al considerarla una Microangiopatía difusa del embarazo se presta atención a los factores angiogénicos y podría ser explicada por el desbalance de los factores angiogénicos circulantes, caracterizado por altos niveles circulantes de tirosincinasa tipo fms 1 soluble, endoglina y otros factores antiangiogénicos, bajos niveles circulantes de factor de crecimiento placentario y factor de crecimiento endotelial vascular.El impacto sistémico es de tal magnitud que los niveles séricos de proteínas de choque térmico son significativamente superiores en los pacientes con el síndrome HELLP. Para el diagnóstico es preciso la presentación clínica y estudios que demuestren la alteración de los parámetros que lo caracteriza. Se presentan alternativas para los exámenes cotidianos como la baja concentración de haptoglobina que puede ser usado para el diagnóstico de hemólisis y es el marcador de preferencia para la misma. La glutatión S-transferasa-a1 plasmático podría ser un indicador más sensible que las transaminasas para diagnóstico temprano de daño hepático, Finalmente se presentan recomendaciones de manejo clínico de la enfermedad, que incluye la necesidad de manejo interdisciplinario en una unidad de cuidados intensivos.PALABRAS CLAVES: SÍNDROME HELLP, FACTORES ANGIOGÉNICOS, ENDOGLINAS, HAPTOGLOBINA, GLUTATIÓN S-TRANSFERASA-A1.ABSTRACTA HELLP syndrome review is present, with greater emphasis to new theories that seek to explain the pathophysiology and management recommendations. The syndrome is characterized by microvascular endothelial damage. However, the pathophysiology of the syndrome is not yet well defined. There is a growing interest in inflammatory cytokines, genetic and environmental factors in the pathogenesis of the same. To consider it a diffuse Microangiopathy pregnancy pays attention to the angiogénics factors and could be explained by the imbalance of the circulating angiogénics, characterized by high circulating levels of tirosincinasa factors type 1 soluble fms and endoglin and other factors antiangiogénicos and lower circulating levels of placental growth factor and vascular endothelial growth factor. The systemic impact is of such magnitude that serum levels of heat shock proteins are significantly higher in patients with the HELLP syndrome. The diagnosis necessitates the clinical presentation and studies showing the alteration of the parameters that characterizes it. Alternatives for everyday exams as the low concentration of which can be used for the diagnosis of hemolysis and is the preference for the same marker haptoglobin are presented. Glutathione S-transferase-a1 plasma could be a more sensitive transaminases for diagnosis early liver damage. Finally recommendations for clinical management of the disease, including the need for interdisciplinary management in an intensive care unit indicator is presented. KEY WORDS: SYNDROME HELLP, ANGIOGÉNICS FACTORS, ENDOGLINAS, HAPTOGLOBIN, GLUTATHIONE S-TRANSFERASE-A1. Correspondencia: Edgar E. Rivas-PerdomoEl Prado. Avenida Cartagena. Nº 32-43 Cartagena- ColombiaTeléfonos (5)6626-872– Celular: 312-670 2992E mail: erivasperdomo@gmail.com

FUNDAÇÃO DE APOIO À PESQUISA DO ESTADO DO RIO DE JANEIRO Esta dissertação trata da modelagem do comportamento dinâmico de cascas cilíndricas laminadas numa faixa considerada de altas frequências onde o comprimento de onda é menor que a espessura da casca. Nestes casos,as teorias tradicionais de cascas tem problemas para representar com acuracidade a resposta dinâmica destas estruturas. Para superar este inconveniente,empregou-se a teoria discreta de Reddy para compósitos laminados.Esta teoria tem como característica o emprego de funções de interpolação para descrever a variação dos campos de deslocamento ao longo da espessura do laminado. Assim, discretizou-se a espessura da casca em lâminas delgadas na direção radial, impondo condições cinemáticas para cada uma delas. Por isto um estado tridimensional de tensões foi assumido para cada lâmina. Esta técnica permitiu a representação de campos de deslocamentos complexos na espessura do laminado representativos daqueles associados às ondas guiadas em altas frequências. A equação de estado que governa a dinâmica da casca foi então obtida no domínio da frequência a partir da aplicação do principio variacional, sendo empregado o método de Riccati para solucionar a mesma. A validação da metodologia proposta nesta dissertação foi feita comparando o espectro de frequência exato com aquele previsto pela teoria aproximada. Desta forma demonstrou-se que a teoria de Reddy é capaz de representar com precisão o comportamento dinâmico da casca cilíndrica na faixa de alta frequência. Além disso, os resultados obtidos na faixa de baixa frequência foram comparados pelo método dos elementos This dissertation addresses the problem of modeling the dynamic response of laminated cylindrical shells in the high frequency range -short wavelength-. In this range of frequency, traditional theories fail to provide an accurate result of the vibratory structural response; So, in order to overcome this shortcoming, we employed a model based on Reddys discrete layer-wise theory. In this method the cylindrical shell is discretized in an arbitrary number of layers in the radial direction, and a three dimensional stress state is assumed in each one. Hence, the application of this method let the representation of complexes displacement elds through the thickness of the shell. This characteristic is representative of displacement elds associated to guided waves in the high frequency range. In the frequency domain,the governing equations were written in a state space form by applying a variational principle. The solution of this state equation was obtained by employing an algorithm based on a discrete version of the Ricatti transformation.To validate the method proposed in this dissertation, comparisons of the present work to the exact wave-dispersion spectra were assessed with excellent results. It indicates that the present method can predict an accurate description of the dynamic response in the high-frequency range. In the low frequency range, the results of the theory of Reddy were compared with the nite element method and, again, a good accuracy was obtained.

The partial biochemical composition of seed flour from 6 varieties of cowpea, Vigna unguiculata (L.) Walp. (Br 14 Mulato, Br 9 Longá, Br 17 Gurguéia, CNC 0434, VlTA 7, and CE 315) was evaluated by determing their lipid content, the fatty acid composition of the oils, the fractionation in different protein (globulins, albumins, glutelins and prolamins), the amount of total soluble protein extracted at different pH, and the presence of hemagglutination activity in the extracts (flour and fractions). The screening for the presence of hemagglutinins (lectins) was carried out by hemagglutination assays whereby the different extracts of each variety (pH 2,6; 7,6 and 9,0) were evaluated by their capacity to clump either normal or proteolytically treated erythroytes from humans (A,B and O blood groups) and rabit. For this porpose, erythrocites treated with bromelain, papain, subtilisin and trypsin were used. In adition, the eletrophoretic pattern under denaturations and reductions conditions of the seed protein was analysed, finaly, the amino acid composition of flour and fraction were determined. The seeds from the 6 varieties investigated showed a low fat content as usually found in a large numbers of legumes seeds, in the range of 1,23 to 1,71% of the dry seed weight. The Br 14 and Br 9 cowpea varieties showed the grater specificactivity in the hemagglutination assays than other varieties; the presence of hemagglutination activity in differents fraction suggest the probably presence of more than one lectins in this varieties. The amount of total and soluble proteins showed in decreasing order (globulins, albumins, glutelins and prolamins) in all varieties studied, the Br 14 and Br 9 showed the major content of globulin fraction. The eletrophoretic profile SDS-PAGE) of seed protein (flour and fraction), showed that eletrophoretic pattern of flour was extremely homogeneus for all varieties, although the eletrophoretic paterns of fractions permited to stablish some differences among varieties principaly in the albumin fraction. Finaly the amino acids compositions showed a very similar pattern in flour and fraction, characterized by a high content of acid and hidroxilic amino acid and a very low content of sulfur amino acid like methionine and cysteine. No presente trabalho farinhas de sementes de 6 variedades de Feijão-de-corda (Vigna unguiculata L. Walp), Br-14 Mulato, Br-9 Longá, Br-17 Gurguéia, CNC-0434, Vita-7 e CE-315, foram submetidas a determinações de teores de lipídeos (totais, saponificáveis e insaponificáveis, além da análise qualitativa e quantitativa de ácidos graxos na fração saponificável), de fracionamento protéico (obtenção das frações albuminas, globulinas, glutelinas ácidas e básicas e prolaminas), de proteínas totais e solúveis a 3 valores de pH (2,6; 7,6; e 9,0), de atividade hemaglutinante dos extratos protéicos (bem como das frações protéicas) contra hemácias de coelho e humanas do sistema ABO, não tratadas e tratadas com enzimas proteolíticas (Bromelaína, Papaína, Subtilisina e Tripsina). Além disto, foi estabelecido também o padrão eletroforético (por eletroforese em gel de poliacrilamida em presença de dodecil sulfato de sódio e 2-mercaptoetanol) das farinhas e de todas as frações. A análise qualitativa e quantitativa das frações lipídicas permitiu estabelecer que nas farinhas das sementes analisadas os lipídeos, como já encontrado para outras leguminosas, se apresentaram em baixos teores percentuais. No que diz respeito à atividade hemaglutinante dos diferentes extratos e frações o que foi observado é que destacadamente as variedades Br-14 e Br-9 apresentaram as maiores atividades específicas. A análise dos resultados de uma forma comparativa e levando-se em conta hemácias tratadas e não tratadas com enzimas proteolíticas leva a concluir que, aparentemente, existe mais de uma lectina nos extratos e frações testadas. Quanto ao fracionamento protéico, tanto as proteínas totais como as proteínas solúveis das diferentes variedades se apresentaram na ordem decrescente de abundância: globulinas, albuminas, glutelinas e prolaminas, sendo que as variedades Br-14 e Br-9 apresentaram o maior conteúdo de globulinas. Com relação a análise eletroforética de farinhas e frações protéicas, foi observado que se por um lado o padrão eletroforético das farinhas é extremamente homogêneo para todas as variedades, por outro lado os perfis eletroforéticos das frações permite estabelecer algumas diferenças entre as variedades, notadamente na fração albumínica das mesmas. Finalmente, em relação à composição de aminoácidos as variedades estudadas se caracterizaram por apresentarem composições bastante semelhantes, com altos conteúdos de aminoácidos ácidos e hidroxilados. Alem disto, todas as variedades se caracterizam por apresentarem baixo teor de aminoácidos sulfurados, como a metionina.

Dengue epidemics in three Mexican cities were investigated with retrospective surveys and virus isolations from acute cases. These epidemics were part of the continuing extension of dengue in Mexico since 1978 after 15 years without transmission. Serotype 1 dengue infection predominated in all epidemics, but in one city, type 2 strains were also isolated. The following findings were consistent in all three cities: 1) illness history provided evidence of presence of infection months before the epidemic became evident, 2) there was a very sharp and progressive increase of dengue illness attack rates by age, 3) there were no interpretable relationships between illness and the presence of different types of breeding sights in the home, 4) socioeconomic status was strongly negatively related to illness, and 5) geographical factors not related to the other measured variables had a strong effect on illness rates reflecting the focality of transmission. In addition, there was evidence of a strong protective effect against illness by the use of mosquito netting or the presence of screens on houses, but these relationships were not universal to all three cities.