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Introduction: The infection of the Zika virus that is endemic in Asia and Africa has now been extended to the Americas. This virus is considered teratogenic, producing a new disease that must be studied in depth. Objetives: This is to identify the clinical expressions found in children from mothers infected with the Zika virus during their pregnancy, and thereby establish the possible association of the time of the prenatal exposure to the Zika virus and the positive clinical findings. Methods: We carried out a transversal descriptive study, with 86 children from women having had an infection by the Zika virus, which were pregnant between January 2016 and December 2018. For the correlation between the presence of positive findings and the trimester of pregnancy at the detection of the infection by the Zika virus, we used Spearman’s correlation with a significance level of p ≤ 0.05. Results: Out of the total number of patients included in the study, 27 expressed a positive clinical finding. Among the neurological disorders, those related to muscular tone were the most frequent (15.48%), followed by psychomotor retardation (10.71%) and microcephaly (9.52%). An association was observed between the prenatal exposure to the Zika virus during the first trimester of pregnancy and the presence of positive clinical findings. Conclusions: There was a prevalence of neurological expressions, followed by visual expressions. The evidence proved that the exposure to the Zika virus during the first trimester of pregnancy had a teratogenic effect.

COVID-19 has had severe consequences worldwide. It has been estimated that the contribution of genetic factors to the disease is about 50%. The A16974C polymorphism of the IL-12 p40 gene has been described as being related to resistance or susceptibility to other infectious diseases; therefore, it is likely that it can also be related to COVID-19. The objective of this study was to describe the relationship between the A16974C polymorphism of the IL12 p40 gene with clinical forms of COVID-19 in Cuban patients. The genotypes of the A16974C polymorphism of gene IL-12 p40 were determined through PCR in 102 persons with a COVID-19 epidemiologic discharge from the hospital. In this research, the CC genotype of this polymorphism was found only in symptomatic cases of this disease; since there are signs of relationship between the A16974C polymorphism of the IL12 p40 gene with clinical forms of COVID-19 in the studied Cuban patients, the variations of this polymorphism may be a predisposing risk factor in the development of COVID-19.

Purpose To determine the relationship between the genotypes of the TaqI polymorphism of VDR gene and the clinical forms of COVID-19 in Cuban patients. Methods TaqI polymorphism was determined by the PCR in 104 Cuban patients, who suffered different clinical forms of COVID-19. Results There was a greater possibility of presenting symptomatic forms [OR = 2.081, 95% CI: 0.243–17.842], even severe [OR = 1.200, 95% CI: 0.217–6.638], related to the tt genotype. Conclusion There are signs of association between the risk of developing COVID-19 and the genotypes of the TaqI polymorphism of the VDR gene in the studied Cuban patients.

The immune response during and after SARS-CoV-2 infection can be complex and heterogeneous, and it can be affected by the severity of the disease. It can also contribute to an unfavorable evolution and bring about short and long term effects. The aim of this study was to characterize the lymphocyte composition according to the severity of COVID-19, as well as its degree of relationship to the specific humoral response to SARS-CoV-2 in convalescents up to 106 days after the infection and in their exposed relatives.An applied research was carried out with a cross-section analytical design, from March 11 to June 11, 2020 in Cuba. The sample consisted of 251 convalescents from COVID-19 over 18 years of age and 88 exposed controls who did not become ill. The B and T cell subpopulations, including memory T cells, as well as the relationship with the humoral immune response against SARS-CoV-2, were identified by flow cytometry and enzyme immunoassay.Convalescent patients, who evolved with severe forms, showed a decrease in frequency and a greater proportion of individuals with values ​​lower than the minimum normal range of B cells, CD3 + CD4 + cells and the CD4 + / CD8 + ratio, as well as a higher frequency and a greater proportion of individuals with values ​​above the normal maximum range of CD3 + CD8 + and NK cells. Convalescent patients with severe forms of COVID-19 that exhibited IgG / RBD titers ≥ 1/200 had a lower frequency of TEMRA CD8 + cells (p = 0.0128) and TEMRA CD4 + (p = 0.0068). IgG / RBD titers were positively correlated with the relative frequency of CD4 + CM T memory cells (r = 0.4352, p = 0.0018).The identified alterations of B and T lymphocytes suggest that convalescent patients with the severe disease could be vulnerable to infectious, autoimmune or autotinflammatory processes; therefore, these individuals need medical follow-up after recovering from the acute disease. Furthermore, the role of T cells CD4 + CM in the production of antibodies against SARS-CoV-2 is confirmed, and it is noted that the defect of memory T cells CD8 + TEMRA could contribute to the development of severe forms of COVID-19.

We evaluated response to a single dose of the FINLAY-FR-1A recombinant dimeric-RBD base vaccine during a phase I clinical trial with 30 COVID-19 convalescents, to test its capacity for boosting natural immunity. This short report shows: a) an excellent safety profile one month after vaccination for all participants, similar to that previously found during vaccination of naïve individuals; b) a single dose of vaccine induces a >20 fold increase in antibody response one week after vaccination and remarkably 4-fold higher virus neutralization compared to the median obtained for Cuban convalescent serum panel. These preliminary results prompt initiation of a phase II trial in order to establish a general vaccination protocol for convalescents.

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1,2,3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500–1,500 and a maximum of 1,530–8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8., This work was supported by a grant from the National Geographic Society to M. Pateman to facilitate analysis of skeletal material from The Bahamas and by a grant from the Italian ‘Ministry of Foreign Affairs and International Cooperation’ (Italian archaeological, anthropological and ethnological missions abroad, DGPSP Ufficio VI). D.R. was funded by NSF HOMINID grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul Allen Foundation, the John Templeton Foundation grant 61220 and the Howard Hughes Medical Institute.

COVID-19 sequelae, or the short-, medium-, and long-term manifestations of the disease are under continuous study. There are currently few reports on the evolution of hematological variables following a demonstrated absence of SARS-CoV-2 after infection.Identify hematological alterations in Cuban adults recovered from SARS-CoV-2 infection, and their relation with disease severity.We selected 348 persons recovered from COVID-19 residing in Havana, Cuba with an RT-PCR study negative for SARS-CoV-2 performed two weeks after hospital discharge; a structured survey was administered to obtain clinical-epidemiological data. Three groups were established according to COVID-19 clinical criteria: asymptomatic, mild/moderately symptomatic, and severely symptomatic, which, in turn, were divided according to hospital discharge date and blood sample collection date. We performed hemograms with differential leukocyte counts and compared results among groups. We then measured the associations between hematological variables, personal medical history, and relevant lifestyle habits (smoking).All hematological variables were within normal reference limits, although men from the group of severely ill patients had increased total leukocytes, neutrophils and lymphocytes, and decreased hemoglobin and eosinophils, which was also evident in those with a recovery time of 31-90 days.The relation between hematological variables and degree of clinical severity offers evidence as to persistence of systemic alterations (possibly inflammatory) associated with viral infection. Their identification and characterization can facilitate personalized patient followup and rehabilitation.

Humans settled the Caribbean ~6,000 years ago, with intensified agriculture and ceramic use marking a shift from the Archaic Age to the Ceramic Age ~2,500 years ago. To shed new light on the history of Caribbean people, we report genome-wide data from 184 individuals predating European contact from The Bahamas, Cuba, Hispaniola, Puerto Rico, Curaçao, and northwestern Venezuela. A largely homogeneous ceramic-using population most likely originating in northeastern South America and related to present-day Arawak-speaking groups moved throughout the Caribbean at least 1,800 years ago, spreading ancestry that is still detected in parts of the region today. These people eventually almost entirely replaced Archaic-related lineages in Hispaniola but not in northwestern Cuba, where unadmixed Archaic-related ancestry persisted into the last millennium. We document high mobility and inter-island connectivity throughout the Ceramic Age as reflected in relatives buried ~75 kilometers apart in Hispaniola and low genetic differentiation across many Caribbean islands, albeit with subtle population structure distinguishing the Bahamian islands we studied from the rest of the Caribbean and from each other, and long-term population continuity in southeastern coastal Hispaniola differentiating this region from the rest of the island. Ceramic-associated people avoided close kin unions despite limited mate pools reflecting low effective population sizes (2Ne=1000-2000) even at sites on the large Caribbean islands. While census population sizes can be an order of magnitude larger than effective population sizes, pan-Caribbean population size estimates of hundreds of thousands are likely too large. Transitions in pottery styles show no evidence of being driven by waves of migration of new people from mainland South America; instead, they more likely reflect the spread of ideas and people within an interconnected Caribbean world.

Sickle cell anemia is the most common hereditary disease in Cuba. On average, 1 in 33 Cubans is a carrier of this severe hemolytic anemia that can cause early death. In early 1980, its incidence in Cuba was calculated at 1 in 1600 births. In 1982, the Cuban public health system established the Sickle Cell Anemia Prevention Program, which aims to prevent the disease through identification of carrier couples and antenatal diagnosis of fetuses with disease-associated genotypes. In 1982-2018, hemoglobin genotypes were tested in 4,847,239 pregnant women. Of these, 168,865 (3.5%) were found to be carriers or to have sickle cell disease. During the same period, 8180 at-risk couples were identified, of whom 79.2% agreed to an antenatal study for detection of the sickle cell gene in the fetus. Among fetuses diagnosed, 20.1% had the SS genotype, the most clinically severe; 76.2% of the associated couples decided to interrupt the pregnancy. This program has resulted in a 3-fold reduction in prevalence of sickle cell disease in Cuba, a 10-fold reduction in the number of infants born with it each year, and a 16-year average increase in life expectancy of sickle cell disease patients of both sexes. Key contributors to these results have been universal screening of pregnant women in primary care, installation of diagnostic laboratories in every province, genetic counseling for couples, testing of fetal DNA (allowing couples to decide whether to continue the pregnancy if the fetus tests positive for the disease) and guaranteed multidisciplinary clinical care for patients. The Cuban experience shows that a middle-income country can mitigate the impact of a genetic disease through a universal preventive program based in primary care, which also pays particular attention to afflicted patients. KEYWORDS Sickle cell anemia, sickle cell disease, sickle cell disorders, hemolytic anemia, sickle cell trait, sickle cell hemoglobin C disease, HbS disease, prevention, antenatal screening, preventive health services, Cuba.

Introduction. A cohort study was carried out at the National Center for Medical Genetics, from July 2017 to June 2018, in 27 patients evaluated in the consultation for the infertile couple at the Hermanos Ameijeiras Hospital. Objective. To establish the relationship of the individual and combined expression of the genotypes of the polymorphisms VEGF (+405 G> C) and TNFα (-308A> G), with the rates of embryo implantation in Cuban patients receiving treatment with in vitro fertilization. Materials and Methods.The identification of the genotypes was carried out using an ARMS PCR. The Hardy-Weinberg equilibrium was determined by applying the Chi square test of goodness of fit from a reference population, and a Principal Component Analysis (PCA) was carried out to evaluate the genotypic population structure with respect to the variables studied. Results. Individuals with combined genotype variant VEGF.CC / TNFα.GG were grouped homogeneously in the PCA model with respect to axis 2, where there was a higher frequency of women with a low implantation rate. In contrast, patients with a genotypic TNFα.AG variant were grouped according to the highest implantation rates. Conclusions. It was concluded that there is a relationship between genotype variants VEGF.CC and TNFα.GG with a low implantation rate, when they are expressed individually or in combination in patients treated with the in vitro fertilization technique, while the individual genotypic variant TNFα. AG is associated with a higher implantation rate.

RESUMEN En Cuba, la atencion a la salud maternoinfantil se sustenta en la prioridad que le otorga el Estado, la ejecucion del Programa Nacional de Atencion Materno Infantil y la garantia de acceso equitativo a los servicios de salud. Este articulo describe la experiencia cubana en este campo, asi como sus principales logros, desafios y lecciones aprendidas. Entre los resultados mas relevantes hasta el 2015 se encuentran la reduccion de la mortalidad infantil y del menor de 5 anos a 4,3 y 5,7 fallecidos por 1 000 nacidos vivos, respectivamente; supervivencia a los 5 anos de 99,4%; mas de 10 controles prenatales por parto; 5,3% de peso bajo al nacer; 99,9% de partos institucionales; y ser el primer pais en validar la eliminacion de la transmision vertical del VIH y la sifilis congenita. Los principales desafios son aumentar la tasa de lactancia materna exclusiva; reducir la anemia por deficit de hierro en ninos y gestantes y el sobrepeso infantil; prevenir los accidentes; y reducir la mortalidad materna, la tasa de fecundidad en las adolescentes y el aborto voluntario. Entre las lecciones aprendidas se destacan la prioridad que el Estado otorga a la salud, la conduccion programatica de la atencion maternoinfantil, la garantia de cobertura universal, la recoleccion sistematica de informacion para la toma de decisiones, la integracion de los sectores y la participacion social en la salud. Sostener y mejorar los resultados alcanzados contribuira al cumplimiento de la Agenda de Desarrollo Sostenible para el 2030.

Background: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. Methods: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Findings: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-I³ and TNF-α. Interpretation: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. Funding: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. Antecedentes: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfeccion, evaluamos la vacuna FINLAY-FR-1A en un ensayo clinico. Metodos: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 anos: convalecientes de COVID-19 leve y convalecientes asintomaticos, ambos con prueba PCR positiva al momento del diagnostico; e individuos con infeccion subclinica detectada por IgG especifica viral. Los participantes recibieron una dosis unica por via intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de union al receptor recombinante dimerico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 dias despues de la vacunacion. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y despues de la vacunacion, se evaluo por ELISA y mediante la prueba de neutralizacion del virus vivo. Tambien se evaluo la respuesta de celulas T efectoras. Registro Publico Cubano de Ensayos Clinicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Resultados: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los mas comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimulo un incremento >21 veces de los anticuerpos IgG anti-RBD 28 dias despues de la vacunacion. La mediana de los titulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron titulos de neutralizacion viral superiores a 1:160 en 24 (80%) de los participantes. Tambien hubo un aumento en las celulas T especificas de RBD que producen IFN-I³ y TNF-α. Interpretacion: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzo eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. Financiamiento: Se recibio un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministerio de Ciencia, Tecnologia y Medio Ambiente, Cuba.

Introduction: Psychiatric genetic research has seen progress in identifying genetic risk variants associated with major mental disorders. Testing with preventive purposes is likely to be offered to high-risk individuals in the near future. It is important that genetic testing and counseling align with the interests of the patients, and these interests are likely to vary among countries and cultures. Aim: The present study aimed to compare the attitudes toward psychiatric genetic research and genetic testing in Denmark and Cuba. Materials and Methods: A survey, culturally adapted for each country, was administered to a pool of students, patients with depression, and the closest relatives of these patients. A total of 491 stakeholders from Denmark and 720 from Cuba were included in the study. Results: Significant differences between the two populations were found for general knowledge about psychiatric genetic research, whom to offer genetic testing, and to whom to entrust with psychiatric genetic information. Cuban stakeholders were more likely to feel uncomfortable about psychiatric genetic research than the Danish stakeholders. This difference might be driven by the characteristics of the health systems, sociocultural factors, and lower genetic literacy in the Cuban population. Conclusion: This study is the first to compare attitudes toward psychiatric genetic testing between a Latin American country and a Nordic country. The results reported could be valuable when designing general guidelines for psychiatric genetic testing in the future.

Background Association studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four Genome-Wide Association Studies (GWAS) have been carried out in these populations. Results We present a GWAS of skin pigmentation in an admixed sample from Cuba (N = 762). Additionally, we conducted a meta-analysis including the Cuban sample, and admixed samples from Cape Verde, Puerto Rico and African-Americans from San Francisco. This meta-analysis is one of the largest efforts so far to characterize the genetic basis of skin pigmentation in admixed populations (N = 2,104). We identified five genome-wide significant regions in the meta-analysis, and explored if the markers observed in these regions are associated with the expression of relevant pigmentary genes in human melanocyte cultures. In three of the regions identified in the meta-analysis (SLC24A5, SLC45A2, and GRM5/TYR), the association seems to be driven by non-synonymous variants (rs1426654, rs16891982, and rs1042602, respectively). The rs16891982 polymorphism is strongly associated with the expression of the SLC45A2 gene. In the GRM5/TYR region, in addition to the rs1042602 non-synonymous SNP located on the TYR gene, variants located in the nearby GRM5 gene have an independent effect on pigmentation, possibly through regulation of gene expression of the TYR gene. We also replicated an association recently described near the MFSD12 gene on chromosome 19 (lead variant rs112332856). Additionally, our analyses support the presence of multiple signals in the OCA2/HERC2/APBA2 region on chromosome 15. A clear causal candidate is the HERC2 intronic variant rs12913832, which has a profound influence on OCA2 expression. This variant has pleiotropic effects on eye, hair, and skin pigmentation. However, conditional and haplotype-based analyses indicate the presence of other variants with independent effects on melanin levels in OCA2 and APBA2. Finally, a follow-up of genome-wide signals identified in a recent GWAS for tanning response indicates that there is a substantial overlap in the genetic factors influencing skin pigmentation and tanning response. Conclusions Our meta-analysis of skin pigmentation GWAS in recently admixed populations provides new insights about the genetic architecture of this complex trait. Electronic supplementary material The online version of this article (10.1186/s12863-019-0765-5) contains supplementary material, which is available to authorized users.

The region surrounding the Caribbean Sea is predominantly composed of island nations for its Eastern part and the American continental coast on its Western part. A large proportion of the population, particularly in the Caribbean islands, traces its ancestry to Africa as a consequence of the Atlantic slave trade during the XVI&ndash, XVIII centuries. As a result, sickle cell disease has been largely introduced in the region. Some Caribbean countries and/or territories, such as Jamaica and the French territories, initiated newborn screening (NBS) programs for sickle cell disease more than 20 years ago. They have demonstrated the major beneficial impact on mortality and morbidity resulting from early childhood care. However, similar programs have not been implemented in much of the region. This paper presents an update of the existing NBS programs and the prevalence of sickle cell disease in the Caribbean. It demonstrates the impact of the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia (CAREST) on the extension of these programs. The presented data illustrate the importance of advocacy in convincing policy makers of the feasibility and benefit of NBS for sickle cell disease when coupled to early care.

Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25-38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.

OBJECTIVE: In an admixed population of older Cubans, the incidence and association of APOE and socio demographic risk factors with dementia incidence was estimated. METHODS: A single-phase survey (baseline) of all over 65-year-olds residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and associations with sociodemographic risk factors of the APOE ε4 genotype. RESULTS: The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95% CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6-23.5). Older age, a family history of dementia and APOE ε4 genotype were independent risk factors for incident 10/66 dementia. APOE genotype was associated cross-sectionally with dementia prevalence, but the effect on the incidence of dementia was attenuated, and only apparent among those in the youngest age group. CONCLUSION: The incidence of dementia in the older Cuban population is relatively high and similar to levels reported in Europe and North-America. The study showed that the relationship between APOE ε4 and incident dementia is stronger in the younger-old than the older-old and that this change must be taken into account in models of dementia. OBJETIVO: Em uma população miscigenada de cubanos idosos, estimamos a incidência de demência e a associação entre o genótipo da APOE e os fatores de risco sociodemográficos na incidência de demência. MÉTODOS: Realizamos uma pesquisa de uma fase (linha de base) de todos os idosos com mais de 65 anos residentes em sete áreas de Cuba (n=2944), de 2003 a 2007. O diagnóstico de demência foi estabelecido de acordo com os critérios do DSM-IV e do 10/66. O genótipo APOE foi determinado em 2520 participantes. Avaliação da incidência foi conduzida 4,5 anos após a linha de base, a fim de estimar a incidência e associações com fatores de risco sociodemográficos e o genótipo APOE ε4. RESULTADOS: A taxa de incidência de demência foi de 9,0 por 1000 pessoas-ano (IC 95% 7,2-11,3) de acordo com o DSM-IV e de 20,5 por 1000 pessoas-ano (IC 95%, 17,6-23,5) de acordo com o 10/66. Idade avançada, história familiar de demência e genótipo APOE ε4 foram fatores de risco independentes para a incidência de demência de acordo com os critérios do 10/66. O genótipo APOE foi associado com a prevalência de demência em estudo transversal, mas o efeito sobre a incidência de demência foi atenuado, e apenas aparente entre aqueles na faixa etária mais jovem. CONCLUSÃO: A incidência de demência na população cubana mais velha é relativamente alta, semelhante às relatadas na Europa e América do Norte. O estudo mostra que a relação entre APOE ε4 incidente e demência é mais forte entre os idosos mais jovens e que esta alteração deve de ser considerada em modelos de demência.

Genetics and genomic medicine in Cuba.

In Cuba, maternal and child health care is based on the priority granted by the State, the implementation of the National Maternal and Child Health Program and the guarantee of equitable access to health services. This article describes the Cuban experience in this field, as well as its main achievements, challenges, and lessons learned. Among the most relevant results up to 2015 are the reduction of infant mortality rate and under-five mortality rate to 4.3 and 5.7 deaths per 1 000 live births, respectively; 5-year survival of 99.4%; more than 10 prenatal check-ups per delivery; 5.3% of low birth weight; 99.9% of institutional births; and being the first country to validate the elimination of mother-to-child transmission of HIV/AIDS and congenital syphilis. The main challenges are to increase the rate of exclusive breastfeeding; to reduce anemia due to iron deficiency in children and pregnant women; to reduce overweight in children; to prevent accidents; and to reduce maternal mortality, adolescent fertility rate, and voluntary abortion. Among the lessons learned are the priority given by the State to health, the programmatic management of maternal and child care, the guarantee of universal coverage, the systematic collection of information for decision-making, the integration of sectors and social participation in health. Sustaining and improving the results achieved will contribute to the fulfillment of the Sustainable Development Agenda for 2030.Em Cuba, os cuidados de saúde materno-infantil baseiam-se na prioridade concedida pelo Estado, na implementação do Programa Nacional de Saúde Materno-Infantil e na garantia de acesso equitativo aos serviços de saúde. Este artigo descreve a experiência cubana neste campo, bem como as principais conquistas, desafios e lições aprendidas. Entre os resultados mais relevantes até 2015 estão a redução da mortalidade infantil e mortalidade em menores de 5 anos para 4,3 e 5,7 mortes por 1 000 nascidos vivos, respectivamente; sobrevivência a 5 anos de 99,4%; mais de 10 exames pré-natal por nascimento; 5,3% do baixo peso ao nascer; 99,9% dos partos institucionais; e seja o primeiro país a validar a eliminação da transmissão materno-infantil de HIV/AIDS e sífilis congênita. Os principais desafios são aumentar a taxa de aleitamento materno exclusivo; reduzir a anemia devido a deficiência de ferro em crianças e mulheres grávidas e reduzir o excesso de peso infantil; prevenir acidentes; e reduzir a mortalidade materna, taxa de fertilidade adolescente e aborto voluntário. Entre as lições aprendidas estão a prioridade dada pelo Estado à saúde, a gestão programática dos cuidados materno e infantil, a garantia de cobertura universal, a coleta sistemática de informações para a tomada de decisões, a integração de setores e a participação social em saúde. Sustentar e melhorar os resultados obtidos contribuirá para o cumprimento da Agenda de Desenvolvimento Sustentável para 2030.

The Cuban Twin Registry is a nation-wide, prospective, population-based twin registry comprising all zygosity types and ages. It was initiated in 2004 to study genetic and environmental contributions to complex diseases with high morbidity and mortality in the Cuban population. The database contains extensive information from 55,400 twin pairs enrolled in the period 2004–2006. Additionally, 2,600 new multiple births have been included from 2007 to date. In the past 4 years, more than 130 studies have been carried out using the registry with a classical genetic epidemiological approach in which concordance rates for monozygotic and dizygotic twins and heritability of various disease traits were estimated. This article summarizes the history, registry's methodology, recent research findings, and future directions of work.

This study was designed to investigate the influence of finding a disease-causing mutation for an early-onset form of Alzheimer's disease, with the intention of taking a presymptomatic genetic test. First-degree relatives of patients with Alzheimer's disease from a large Cuban family with a newly described mutation in presenilin 1 gene were interviewed before and after molecular studies. Significant differences were observed regarding the knowledge of the disease (p = 0.0004), interest in presymptomatic testing (p = 0.000), and possible reproductive behavior (p = 0.0087) in the same individuals in two different periods, 1997 and 2007. Our results show that there is a marked difference in the attitudes concerning genetic testing when individuals gain more knowledge about the disease and when there is more certainty about the test.

I was part of a people-to-people tour of Havana, Cuba during the first week in April 2014. Among the many highlights of that adventure were an informal meeting with Dr Beatriz Marcheco-Teruel, from Cuba's National Center for Medical Genetics, and a visit to the famous ‘Street of Twins’. A fortuitous meeting with parents of twins in the fishing town of Jaimanitas was also an extraordinary event. The Cuban experience is followed by summaries of recent twin research, covering umbilical cord entanglement, the heritability of clubfoot and school separation policies for twins. Media reports include twins reunited at age 78, the future of UCLA's twin basketball players, MZ twins born holding hands, a twin conflict over beer and a pair of American Psychological Association honors for Drs Nancy L. Segal and Thomas J. Bouchard, Jr.

We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in order to evaluate admixture using uniparental markers. Finally, we analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation. In the total sample, the average European, African and Native American contributions as estimated from autosomal AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed relatively higher African and Native American contributions than the Western provinces. In particular, the highest proportion of African ancestry was observed in the provinces of Guantánamo (40%) and Santiago de Cuba (39%), and the highest proportion of Native American ancestry in Granma (15%), Holguín (12%) and Las Tunas (12%). We found evidence of substantial population stratification in the current Cuban population, emphasizing the need to control for the effects of population stratification in association studies including individuals from Cuba. The results of the analyses of uniparental markers were concordant with those observed in the autosomes. These geographic patterns in admixture proportions are fully consistent with historical and archaeological information. Additionally, we identified a sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side, and higher Native American and African contributions from the maternal side. This sex-biased contribution was particularly evident for Native American ancestry. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with melanin levels in the sample., Author Summary Cuba is the largest island of the Greater Antilles and its most populous country. The post-Columbian history of the Caribbean has been marked by the encounter of people from different continents. Here, we present an admixture analysis of 1,019 individuals from all the provinces of Cuba, using autosomal, mtDNA and Y-chromosome markers. We also analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation (melanin index). The highest proportions of African ancestry were observed in the Southeastern provinces of Santiago de Cuba and Guantánamo, and the highest proportions of Native American ancestry were found in the Eastern provinces of Granma, Holguín and Las Tunas. Similar geographic patterns were observed in the analyses of the uniparental markers. Additionally, by comparing the autosomal and uniparental admixture proportions, we identified a clear sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side than the maternal side, and conversely higher Native American and African contributions from the maternal side than the paternal side. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 show a strong association with skin pigmentation in the sample.

Background The prevalence and incidence of dementia are low in Nigeria, but high among African-Americans. In these populations there is a high frequency of the risk-conferring APOE-e4 allele, but the risk ratio is less than in Europeans. In an admixed population of older Cubans we explored the effects of ethnic identity and genetic admixture on APOE genotype, its association with dementia, and dementia prevalence. Methods A cross-sectional catchment area survey of 2928 residents aged 65 and over, with a nested case-control study of individual admixture. Dementia diagnosis was established using 10/66 Dementia and DSM-IV criteria. APOE genotype was determined in 2520 participants, and genetic admixture in 235 dementia cases and 349 controls. Results Mean African admixture proportions were 5.8% for 'white', 28.6% for 'mixed' and 49.6% for 'black' ethnic identities. All three groups were substantially admixed with considerable overlap. African admixture was linearly related to number of APOE-e4 alleles. One or more APOE-e4 alleles was associated with dementia in 'white' and 'black' but not 'mixed' groups but neither this, nor the interaction between APOE-e4 and African admixture (PR 0.52, 95% CI 0.13-2.08) were statistically significant. Neither ethnic identity nor African admixture was associated with dementia prevalence when assessed separately. However, considering their joint effects African versus European admixture was independently associated with a higher prevalence, and 'mixed' or 'black' identity with a lower prevalence of dementia. Conclusions APOE genotype is strongly associated with ancestry. Larger studies are needed to confirm whether the concentration of the high-risk allele in those with African ancestry is offset by an attenuation of its effect. Counter to our hypothesis, African admixture may be associated with higher risk of dementia. Although strongly correlated, effects of admixture and ethnic identity should be distinguished when assessing genetic and environmental contributions to disease risk in mixed ancestry populations.

We present results from a genome-wide scan of a six generation pedigree with 28 affected members with apparently dominant bipolar I disorder from eastern Cuba. Genotypes were obtained using the early access version of the Genechip Mapping 10K Xba array from AFFYMETRIX. Parametric and non-parametric linkage analyses under dominant and recessive models were performed using GENEHUNTER v2.1r5. Two phenotypic models were included in the analyses: bipolar I disorder and recurrent depressive disorder, or bipolar I disorder only. LOD scores were calculated for the entire family combined, and for four subdivisions of the family. For the entire family a suggestive parametric LOD score was obtained under the dominant model and the broader phenotype at 14q11.2-12 (LOD = 2.05). In the same region, a non-parametric LOD score close to genome-wide significance was also obtained, based on the entire family (NPL = 7.31, P-value = 0.07). For two individual branches of the pedigree, genome-wide significance (P < 0.005) was obtained with NPL scores of 8.71 and 12.99, respectively, also in the same region on chromosome 14. Chromosome 5q21.3-22.3 also showed close to genome-wide significant linkage for the complete pedigree (NPL = 7.26, P = 0.07), also supported by significant linkage in one individual branch (NPL = 9.86, P < 0.005). In addition, genome-wide significant nonparametric results (P-values