ABSTRACT In Cuba, newborn screening (NBS) for cystic fibrosis (CF) was introduced in January 2019. The results from the first three years of the CF NBS program are presented. An IRT/IRT protocol was followed using a cut-off value of 50 ng/mL. In this period 281,717 neonates were screened, 2,197 samples had increased IRT values, and a second sample was necessary (recall rate=0.78%). In 686 (0.24%) neonates, IRT was still elevated, and they were referred for clinical evaluation. Twenty-one children were confirmed by sweat test and molecular biology. Eighteen newborns presented variant F508del. A false negative case was reported. Demographic data of 32,764 neonates were collected. The average age of sampling was six days with results available at 11 days of life, but 1.7% of the samples were collected 20 days after birth. The mean IRT value was 12.7±11.7 ng/mL (ranging 0-283 ng/mL) with a calculated 98.5 percentile value of 42.4 ng/mL. On average, the samples were processed five days after collection and two days after they were received at the laboratory. Although CF NBS program in Cuba is just beginning, it can be predicted that CF will be one of the most frequent inherited-metabolic diseases in the Cuban population.

This work describes the synthesis of new 1,3-benzoxathiol-2-one sulfonamides and evaluation of their ability to inhibit some in vitro (coagulant, proteolytic and hemolytic) and in vivo (hemorrhagic, edematogenic and lethality) toxic activities of Bothrops jararaca and Bothrops jararacussu venoms. Compounds have been synthesized from the coupling of intermediate 5-amino-6 methoxybenzo[d][1,3]oxathiol-2-one 4 with benzenesulfonyl chlorides. Characterization of the products was achieved by nuclear magnetic resonance (NMR) and electrospray ionization mass spectra (ESI-MS) techniques. Biological assay results have shown that most of compounds inhibited the main toxic activities of the venom of the two snake species. Compound 5b (N-(6 methoxy-2 oxobenzo[d][1,3]oxathiol-5-yl)-4-nitrobenzenesulfonamide) was the most efficient in inhibiting hemolysis of B. jararaca, and coagulation and proteolysis induced by both venoms. For in vivo activities, all compounds inhibited the edema, from 35 to 72%, and most of them exhibited antihemorrhagic and antilethality activities. Thus, the results pointed to the biological potential of these compounds, being promising molecules to treat envenomation by these snakes as well as to aid the current antivenom serum therapy.

Resumen El presente trabajo de investigación tiene como objetivo analizar las estrategias de inclusión laboral de excombatientes en proceso de reintegración a la dinámica empresarial implementadas por tres empresas colombianas. El estudio es de carácter descriptivo con enfoque mixto (cualitativo y cuantitativo). La población estuvo constituida por setenta y un empleados (autodefensas y guerrilleros desmovilizados) a quienes se les aplicó una encuesta y por tres directivos de gestión humana a quienes se les entrevistó. Se indagó por las dimensiones: Inclusión laboral sostenible, equidad en la contratación, el trato y herramientas administrativas; Clima laboral, satisfacción con la organización y experiencias y sentidos del trabajo. Los resultados obtenidos en términos generales, permitieron establecer que los excombatientes experimentan satisfacción con las políticas implementadas por las empresas para generar programas de inclusión laboral sostenibles, para que cada vez más personas puedan reintegrarse a la vida civil. Esta investigación cobra relevancia por los aportes que brinda a la agencia para la reincorporación y normalización, a las empresas y en general a todas las organizaciones públicas o privadas interesadas en contratar personas desmovilizadas que pertenecieron a grupos al margen de la ley.

Abstract The present research work aims to analyze the strategies for the labor inclusion of ex-combatants undergoing the reintegration process to business dynamics implemented by three Colombian companies. The study is descriptive with a mixed approach (qualitative and quantitative). The sample was made up of seventy-one employees (self-defense groups and demobilized guerrillas) who were surveyed, and three human resource managers who were interviewed. The following dimensions were investigated: Sustainable labor inclusion, fair recruitment, treatment, and administrative tools; Work climate, satisfaction with the organization, and experiences and senses of work. Overall, the results obtained allowed us to establish that ex-combatants experience satisfaction with the policies implemented by companies to generate sustainable labor inclusion programs so that increasingly more people can reintegrate into civilian life. This research study is relevant given the contributions it makes to the Agency for Reincorporation and Normalization (ARN), to companies, and in general to all public or private organizations interested in hiring demobilized individuals who belonged to groups outside the law.

RESUMO O objetivo da pesquisa foi descrever e analisar as relações interpessoais entre alunos com deficiência intelectual (DI) e seus colegas de sala de aula em contextos escolares inclusivos. Trata-se de pesquisa quantitativa e qualitativa realizada em salas dos primeiros anos do Ensino Fundamental. Foram levantados indicadores da participação do aluno com DI nas relações interpessoais, por meio de entrevistas junto a 268 alunos, sendo 13 com DI. A partir desses resultados, seis alunos com DI foram eleitos como alvo em sessões de observação sistemática. Observou-se que as relações interpessoais sofreram influência: da atuação das professoras regentes e dos apoios educacionais; da competência social dos alunos com DI e das características dos mesmos; do ambiente da sala de aula. Acredita-se que, por meio do investimento na promoção de habilidades sociais na escola, será possível contribuir para a construção de um ambiente propício a práticas educacionais inclusivas.

ABSTRACT The aim of the present research work was to describe and analyze the interpersonal relations between students with intellectual disabilities (ID) and their classmates in inclusive school contexts. This is a quantitative and qualitative research work carried out in classrooms in the first years of elementary school. Indicators for the students with ID participation in interpersonal relations were raised through interviews with 268 students, 13 with ID. Based these results, six students with ID were chosen as targets for systematic observation sessions. It was observed that interpersonal relationships were influenced by: the role of the lead teachers and educational supporters; the ID students’ social competence and their characteristics; the classroom environment. It is believed that, by means of investment in the promotion of social skills at school, it will be possible to contribute to the construction of an appropriate environment to inclusive educational practices.

RESUMEN El objetivo de la investigación fue describir y analizar las relaciones interpersonales entre alumnos con deficiencia intelectual (DI) y sus compañeros de sala de clase en contextos escolares inclusivos. Se trata de investigación cuantitativa y cualitativa realizada en salas de los primeros cursos de la enseñanza básica. Se recompilaron indicadores de la participación del alumno con DI en las relaciones interpersonales, por intermedio de entrevistas junto a 268 alumnos, 13 con DI. A partir de esos resultados, seis alumnos con DI fueron electos como diana en sesiones de observación sistemática. Se tuvo por observo que las relaciones interpersonales sufrieron influencia: de la actuación de las profesoras regentes y de los apoyos educacionales; de la competencia social de los alumnos con DI y de las características de ellos; del ambiente de la sala de clase. Se cree que, por intermedio de la inversión en la promoción de habilidades sociales en la escuela, será posible contribuir para la construcción de un ambiente propicio a las prácticas educacionales inclusivas.

INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVES Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients’ clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and transmission or clinical progression, although the proportion of deaths was higher for subtype B. Among those who died during the study period, there were no differences between subtypes in the mean time from HIV or AIDS diagnosis to death. CONCLUSIONS Our results suggest that B and non-B HIV-1 subtypes found in Cuba do not differ in transmissibility and in clinical disease progression.

An immunochromatographic lateral flow assay for the serological diagnosis of brucellosis in cattle, swine, sheep and humans was developed. The test evaluation was carried out with 259 serum samples from the four mentioned species; 67 positive and 192 negative by rose bengal test (RB). Interpretation of the test was performed by visual inspection after 15-20 minutes of the samples being applied. The test was considered negative if only the control line appeared and positive when the test line also appeared. In general and for each group of sera, sensitivity and diagnostic specificity and sensitivity and relative specificity to RB test were determined. Kappa index (k) was also calculated to estimate the agreement between the two tests. The diagnostic sensitivity and specificity obtained were 98.5% and 99.47%, respectively. The sensitivity and specificity relative to RB were 95.65% and 99.95% respectively, with a k value of 0.95, which meant a very good agreement with respect to the RB. The sensitivity of the system to sera cattle, pigs, sheep and humans was 98.3%, 100%, 100% and 100% respectively. Likewise the test showed high levels of specificity in this group of sera. The satisfactory performance and simplicity of this assay allow recommending its use as another tool for the screening of antibodies against Brucella sp. in the serological diagnosis of brucellosis in the animal species studied.

Se desarrolló un sistema inmunocromatográfico de flujo lateral para el diagnóstico serológico de la brucelosis en bovinos, porcinos, ovinos y humanos. En la evaluación se emplearon 259 muestras de sueros de las cuatro especies mencionadas, 67 positivos y 192 negativos por la prueba de Rosa de Bengala (RB). La interpretación del ensayo se realizó por inspección visual entre 15-20 minutos de aplicadas las muestras. La prueba se consideró negativa si solo aparecía la línea de control, y positiva cuando aparecían la línea control y la de prueba. Para cada uno de los grupos de sueros se determinó la sensibilidad y especificidad diagnósticas y la sensibilidad y especificidad relativas a la prueba de RB. Además, se calculó el índice Kappa (k) para estimar la concordancia entre ambas pruebas. Se obtuvieron 98,5% y 99,47% de sensibilidad y especificidad diagnósticas, respectivamente. La sensibilidad y especificidad relativas a RB fue del 95,65% y 99,95% respectivamente, con un valor de k de 0,95, lo que significó una concordancia muy buena con respecto a la RB. La sensibilidad del sistema frente a sueros bovinos, porcinos, ovinos y humanos fue de 98,3%, 100%, 100% y 100%, respectivamente. De igual forma, el ensayo mostró altos niveles de especificidad en este grupo de sueros. Los resultados satisfactorios de desempeño y la simplicidad del ensayo permiten recomendar su empleo para el pesquisaje de anticuerpos contra Brucella sp. en las especies estudiadas como otra herramienta para el diagnóstico serológico de la brucelosis.

Background Snakebite is considered a neglected tropical disease by the World Health Organization. In Brazil, about 70% of the envenomation cases are caused by Bothrops snakes. Its venom may provoke hemorrhage, pain, necrosis, hemolysis, renal or cardiac failure and even death in victims. Since commercial antivenom does not efficiently neutralize the local toxic effects of venoms, natural products have been tested in order to provide alternative or complementary treatment to serum therapy. Therefore, the present study aimed to evaluate the ability of the seaweed Plocamium brasiliense and its active derivatives to neutralize hemorrhagic, edematogenic, hemolytic, coagulant and proteolytic activities of B. jararaca venom. Methods Specimens of P. brasiliense were collected in Rio de Janeiro state, Brazil, dried and submitted to oil extraction using four solvents of increasing polarities, n-hexane (HEX), dichloromethane (DCM), ethyl acetate (ETA) and hydroalcoholic solution (HYD). The solvents were evaporated, yielding HEX, DCM, ETA and HYD extracts. Further, all extracts were dissolved in dimethylsulfoxide. In addition, two monoterpenes (8-bromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene and 1,8-dibromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene) and a cholesterol fraction were isolated from the extract of P. brasiliense prepared in hexane. Algal samples were incubated for 30 minutes with B. jararaca venom, and then tested for lethality; hemorrhagic, edematogenic, hemolytic, coagulant and proteolytic effects. Results Most of the algal extracts inhibited the toxic effects with different potencies. The DCM extract was the most effective, since it inhibited all types of toxic activity. On the other hand, the HYD extract failed to inhibit any effect. Moreover, the isolated products inhibited proteolysis and protected mice from hemorrhage in 30% of the cases, whereas 8-bromo-3,4,7-trichloro-3,7-dimethyl-1E, 5E-octadiene inhibited 100% and 20% of the hemorrhagic and proteolytic activities, respectively. None of the algal products were toxic to mice. Conclusion Seaweeds may be a promising source of inhibitors against toxic effects caused by B. jararacaenvenomation, which may contribute to antivenom treatment.

INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection. OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba. METHODS HIV-2 reactivity was studied using the ELISA DAVIH-VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba's National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients. RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2-positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup. CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH-VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results.

Introduction: antigen immobilization in solid supports is used for the development of several immunoassays. One of the first technologies developed was the protein adsorption by direct application to nitrocellulose. Objective: to standardize the immobilization of a synthetic peptide of the HIV-2 transmembrane protein gp36 to nitrocellulose support for diagnostic purposes and to evaluate the performance parameters in a group of serum samples with recognized interesting reactivity. Methods: the peptide was freely immobilized, conjugated to bovine serum albumin (BSA) and to keyhole limpet hemocyanin (KLH) as carrier proteins. Immobilization parameters were analyzed and then, the optimal immobilization alternative was determined. Using the chosen variant, the diagnostic sensitivity and specificity against reference panels of the AIDS Research Laboratory were evaluated. Analytical specificity was evaluated with reactive samples to HIV-1 and HTLV-I. Results: the analysis of the immobilized peptide variants to nitrocellulose membranes showed that the gp36 peptide-BSA was the one that succeeded in setting the greatest differentiation between positive and negative samples. There were observed 100% sensitivity, 95.2% diagnostic specificity and 100% analytical specificity. Conclusions: the gp36-BSA peptide immobilized on nitrocellulose membranes showed efficacy for the serological diagnosis of HIV-2, which will allow considering this peptide for diagnostic uses in systems with nitrocellulose based solid phase.

Introducción: la inmovilización de antígenos a soportes sólidos se utiliza para el desarrollo de diversos inmunoensayos. Una de las primeras tecnologías desarrolladas fue la adsorción de proteínas por aplicación directa sobre la nitrocelulosa. Objetivo: normalizar la inmovilización de un péptido sintético de la proteína de transmembrana gp36 del VIH-2, a un soporte de nitrocelulosa para fines diagnósticos y evaluar los parámetros de desempeño en un grupo de muestras de sueros con reactividad de interés conocida. Métodos: el péptido se inmovilizó de forma libre, conjugado a la albúmina de suero bovina (BSA) y a la hemocianina de lapa marina (KLH) como proteínas portadoras. Se analizaron los parámetros de inmovilización y se determinó la variante óptima. Con la variante escogida se evaluó la sensibilidad y especificidad diagnóstica frente a paneles de referencia del Laboratorio de Investigaciones del SIDA. La especificidad analítica se evaluó con muestras reactivas a VIH-1 y HTLV-I. Resultados: el análisis de las variantes de péptido inmovilizadas a las membranas de nitrocelulosa, demostró que el péptido gp36-BSA, fue el que logró la mayor diferenciación entre muestras positivas y negativas. Se obtuvo 100 % de sensibilidad y 95,2 % de especificidad diagnóstica, así como 100 % de especificidad analítica. Conclusiones: el péptido gp36-BSA inmovilizado en membranas de nitrocelulosa es eficaz en el diagnóstico serológico del VIH-2, lo cual permitirá considerarlo para su empleo con fines diagnósticos en sistemas que utilicen como fase sólida la nitrocelulosa.

OBJECTIVE: ELISA DAVIH-Ag p24 was modified by introducing heat dissociation of plasma samples and a tyramine/streptavidine-peroxidase amplification system, with the objective of increasing sensitivity. METHODS: Between-assay repeatability was determined in amplified DAVIH-Ag p24. Thirty two plasma samples from HIV-1-infected individuals classified in three clinical categories (AIDS case, asymptomatic and minor opportunistic infections) were evaluated. RESULTS: the variation coefficient ranged 4-10.3 % in between-assay repeatability. With the amplified DAVIH-p24 Ag, the p24 antigen detection level increased to 0.5 pg/mL. Amplified DAVIH-p24 Ag reached 66 % sensitivity whereas standard DAVIH-p24 Ag sensitivity rate was 31 %. CONCLUSIONS: This preliminary study proved that the introduction of new modifications in amplified DAVIH-p24 Ag managed to increase the p24 antigen detection levels and to gain sensitivity.

OBJETIVO: se modificó el ELISA DAVIH-Ag P24 con la introducción de la disociación por calor de las muestras de plasma y el empleo de un sistema de amplificación biotina-tiramina/estreptavidina-peroxidasa, para incrementar su sensibilidad. MÉTODOS: se determinó la repetibilidad interensayo en el DAVIH-Ag P24 amplificado. Se evaluaron 32 muestras de plasma de individuos infectados por el VIH-1 en 3 categorías clínicas (caso SIDA, asintomáticos y con infecciones oportunistas menores). RESULTADOS: en la determinación de la repetibilidad interensayo se obtuvo un coeficiente de variación entre 4 y 10,3 %. Con el DAVIH-Ag P24 amplificado se incrementó el nivel de detección de P 24 hasta 0,5 pg/mL. El DAVIH-Ag P24 amplificado alcanzó 66 % de sensibilidad, mientras que el DAVIH-Ag P24 obtuvo 31 %. CONCLUSIONES: este estudio preliminar permitió demostrar que la incorporación de las nuevas modificaciones al sistema DAVIH-Ag P24 amplificado logró aumentar los niveles de detección de P24 y ganar en sensibilidad.

The results of the design and evaluation of DAVIH VIH-2 diagnosing system, an indirect Elisa for screening of HIV-2 antibodies, which uses a HIV-2 glycoprotein gp36 synthetic peptide in its solid phase, were exposed. In the system evaluation using WHO reference panels, 100 % sensitivity, 99,81 % specificity, 99,81% efficacy and very good concordance level (kappa = 0.978) were attained. Serum samples of 959 individuals with undetermined or negative results to the HIV-1 antibodies confirmation (DAVIH blot) were evaluated by the DAVIH VIH-2 system. Twenty four samples were reactive, six of which had confirmed HIV-2 antibodies. These results allowed recommending the introduction of this diagnostic kit in the HIV infection diagnosing algorithm in Cuba.

Se expusieron los resultados del diseño y la evaluación del diagnosticador DAVIH VIH-2, sistema ELISA indirecto diseñado para el pesquisaje de anticuerpos al VIH-2, que utiliza en su fase sólida un péptido sintético de la proteína de envoltura gp36 del VIH-2. La evaluación del desempeño del sistema se realizó utilizando paneles de referencia de la OMS y se determinó que la sensibilidad fue 100 %, la especificidad 99,81 %, la eficacia 99,81 % y la concordancia muy buena (índice kappa= 0,978). Las muestras de suero de 959 personas con resultados indeterminados o negativos a la confirmación de anticuerpos al VIH-1 (DAVIH-Blot) se evaluaron en el sistema DAVIH VIH-2. Resultaron reactivas al sistema 24 muestras, confirmándose la presencia de anticuerpos al VIH-2 en 6 de ellas. Estos resultados permitieron sugerir la introducción de este diagnosticador en el algoritmo de diagnóstico de la infección por VIH en Cuba.

The objective of this report was to evaluate oral fluid and urine as optional samples for HIV-1 confirmatory test using DAVIH-BLOT system (Laboratorios DAVIH, La Habana, Cuba), for which they were compared with their corresponding serum samples in a group of 125 individuals. In band pattern analysis, predominant antibodies in positives oral fluid and urine samples against p34, p68, gp41, gp120, were no different from their corresponding sera according to the proportion comparison test (p<0,001). Relative sensitivity and specificity of this system were 100 % in oral fluid and 98, 75% and 100% in urine samples respectively. These results support optional use of oral fluid and urine that, with slight modifications in the diagnostic system, can be applied for HIV-1 antibody confirmation testing.

Se evaluó el fluido oral y la orina como muestras opcionales en el diagnóstico confirmatorio del VIH-1 con el sistema DAVIH-BLOT (Laboratorios DAVIH, La Habana, Cuba), para lo cual se comparó con las correspondientes muestras de sueros en un grupo de 125 individuos. En el análisis de los patrones de bandas reveladas, los anticuerpos predominantes en las muestras positivas de fluido oral y orina contra la p34, p68, gp41 y gp120, no tuvieron diferencias con sus correspondientes sueros según la prueba de comparación de proporciones (p< 0,001). La sensibilidad y especificidad relativas del sistema resultaron de 100 % en el análisis del fluido oral; 98,75 y 100 %, respectivamente, en las muestras de orina. Estos resultados apoyan el empleo opcional del fluido oral y la orina que, con ligeras modificaciones introducidas en el sistema diagnóstico, pueden aplicarse para la confirmación de anticuerpos contra el VIH-1.