Torque Teno Virus (TTV) in Renal Transplant Recipients: Species Diversity and Variability.

Torque Teno Virus (TTV) is a nonpathogenic and ubiquitous ssDNA virus, a member of the Anelloviridae family. TTV has been postulated as a biomarker in transplant patients. This study aimed to determine the TTV species diversity and variability in renal transplant recipients and to associate species diversity with the corresponding TTV viral load. From 27 recipients, 30 plasma samples were selected. Viral load was determined using two real-time PCR assays, followed by RCA-NGS and ORF1 phylogenetic analysis. The TTV diversity was determined in all samples. Variability was determined in three patients with two sequential samples (pre- and post-transplantation). Most of the samples presented multiple TTV species, up to 15 different species were detected. In the pre-transplant samples (n = 12), the most prevalent species were TTV3 (75%) and TTV13 (75%), and the median number of species per sample was 5 (IQR: 4-7.5). TTV3 was also the most prevalent (56%) in the post-transplant samples (n = 18), and the median number of species was 2 (IQR: 1.8-5.5). No significant correlation between the number of species and viral load was found. The number and type of TTV species showed total variability over time. We report high TTV species diversity in Argentinian recipients, especially in pre-transplant period, with total intra-host variability. However, we found no significant correlation between this high diversity and TTV viral load.

Diseases during pregnancy in a large unselected South American sample.

OBJECTIVE: Our aim was to describe the prevalence of diseases during pregnancy and the association between fetal exposure to the most frequent maternal diseases and the risk of preterm (PTB) and/or small for gestational age (SGA) newborns in an unselected sample of women who gave birth in South American countries. METHODS: We conducted a descriptive, cross-sectional study including 56,232 mothers of non-malformed infants born between 2002 and 2016, using data from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Diseases with higher- than-expected PTB/SGA frequencies were identified. Odds ratios of confounding variables for diseases and birth outcomes were calculated with a multivariable logistic regression. RESULTS: Of the 14 most reported diseases, hypertension, genitourinary infection, epilepsy, hypothyroidism, diabetes, and HIV/AIDS showed higher PTB and/or SGA frequencies. Advanced and low maternal age, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with PTB, while advanced maternal age, primigravidity, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with SGA. After adjusting for the associated variables, the identified illnesses maintained their association with PTB and all, except epilepsy, with SGA. CONCLUSION: The description of an unselected population of mothers allowed identifying the most frequent diseases occurring during gestation and their impact on pregnancy outcomes. Six diseases were associated with PTB and two with SGA newborns. To the best of our knowledge, there are no similar reports about women not intentionally selected by specific diseases during pregnancy in South American populations.

Diseases during pregnancy in a large unselected South American sample / Prevalência de doenças durante a gravidez em uma grande amostra sul-americana não selecionada

ABSTRACT Objective: Our aim was to describe the prevalence of diseases during pregnancy and the association between fetal exposure to the most frequent maternal diseases and the risk of preterm (PTB) and/or small for gestational age (SGA) newborns in an unselected sample of women who gave birth in South American countries. Methods: We conducted a descriptive, cross-sectional study including 56,232 mothers of non-malformed infants born between 2002 and 2016, using data from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Diseases with higher- than-expected PTB/SGA frequencies were identified. Odds ratios of confounding variables for diseases and birth outcomes were calculated with a multivariable logistic regression. Results: Of the 14 most reported diseases, hypertension, genitourinary infection, epilepsy, hypothyroidism, diabetes, and HIV/AIDS showed higher PTB and/or SGA frequencies. Advanced and low maternal age, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with PTB, while advanced maternal age, primigravidity, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with SGA. After adjusting for the associated variables, the identified illnesses maintained their association with PTB and all, except epilepsy, with SGA. Conclusion: The description of an unselected population of mothers allowed identifying the most frequent diseases occurring during gestation and their impact on pregnancy outcomes. Six diseases were associated with PTB and two with SGA newborns. To the best of our knowledge, there are no similar reports about women not intentionally selected by specific diseases during pregnancy in South American populations.

RESUMO Objetivo: Descrever a prevalência de doenças durante a gravidez e a associação entre a exposição fetal às doenças maternas mais prevalentes e o risco de recém-nascidos prematuros (PP) e/ou pequenos para a idade gestacional (PIG) em uma amostra não selecionada de mulheres que deram à luz em países da América do Sul. Métodos: Estudo descritivo transversal que incluiu 56.232 mães de crianças não malformadas nascidas entre 2002 e 2016, utilizando dados do Estudo Colaborativo Latino-americano de Malformações Congênitas (ECLAMC). Foram identificadas as doenças com maior número de casos observado/esperado de PP/PIG. O esperado foi obtido dos controles sem doenças. Odds ratios para variáveis de confusão de doença e eventos ao nascimento foram calculadas usando regressão logística multivariada. Resultados: Das 14 doenças mais referidas, hipertensão, infecção geniturinária, epilepsia, hipotireoidismo, diabetes e HIV/AIDS apresentaram maiores frequências de PP e/ou PIG. Idade materna nos dois extremos, perda fetal prévia, baixo nível socioeconômico e ascendência afro-americana foram associados a PP, enquanto idade materna avançada, primigravidez, perda fetal prévia, baixo nível socioeconômico e ascendência afro-americana foram associados a PIG. Após ajuste para as variáveis associadas, as doenças identificadas mantiveram associação com PP e todas, exceto epilepsia, com PIG. Conclusão: A descrição de uma população não selecionada de gestantes possibilitou identificar as doenças mais frequentes e seu impacto nos resultados adversos na gravidez. Seis doenças foram associadas a PP e duas a recém-nascidos PIG. Até onde sabemos, não há relatos semelhantes sobre mulheres não selecionadas intencionalmente por doenças específicas durante a gravidez em populações sul-americanas.

Individual deprivation, regional deprivation, and risk for oral clefts in Argentina.

OBJECTIVE: The aim of this study was to analyze the effects of individual low socioeconomic status (SES) and deprived geographical area (GA) on the occurrence of isolated cleft lip with or without cleft palate (CL±P) in Argentina. METHODS: This case-control study included 577 newborns with isolated CL±P and 13 344 healthy controls, born between 1992 and 2001, from a total population of 546 129 births in 39 hospitals in Argentina. Census data on unsatisfied basic needs were used to establish the degree of geographical area deprivation. An SES index for each individual was established, using maternal age, gravidity, low paternal and maternal education, and low-level paternal occupation. Logistic regression was used to assess the effects of low SES and of deprived GA on CL±P. RESULTS: A slightly increased risk of CL±P was observed in mothers with a low SES, while a deprived GA showed no effect. Native ancestry, acute maternal illnesses, and poor prenatal care were significant risk factors for CL±P for the mothers with low SES, after using propensity scores to adjust for the demographic characteristics in cases and controls. CONCLUSIONS: Low individual SES slightly increased the risk for CL±P, but a deprived GA did not have that effect. There was no interaction between individual SES and deprived GA. Factors related to low individual SES-including poor prenatal care, low parental education, lack of information, and lifestyle factors-should be primarily targeted as risk factors for CL±P rather than factors related to a deprived place of residence.

Individual deprivation, regional deprivation, and risk for oral clefts in Argentina

Objective. The aim of this study was to analyze the effects of individual low socioeconomic status (SES) and deprived geographical area (GA) on the occurrence of isolated cleft lip with or without cleft palate (CL±P) in Argentina. Methods. This case-control study included 577 newborns with isolated CL±P and 13 344 healthy controls, born between 1992 and 2001, from a total population of 546 129 births in 39 hospitals in Argentina. Census data on unsatisfied basic needs were used to establish the degree of geographical area deprivation. An SES index for each individual was established, using maternal age, gravidity, low paternal and maternal education, and low-level paternal occupation. Logistic regression was used to assess the effects of low SES and of deprived GA on CL±P. Results. A slightly increased risk of CL±P was observed in mothers with a low SES, while a deprived GA showed no effect. Native ancestry, acute maternal illnesses, and poor prenatal care were significant risk factors for CL±P for the mothers with low SES, after using propensity scores to adjust for the demographic characteristics in cases and controls. Conclusions. Low individual SES slightly increased the risk for CL±P, but a deprived GA did not have that effect. There was no interaction between individual SES and deprived GA. Factors related to low individual SES—including poor prenatal care, low parental education, lack of information, and lifestyle factors—should be primarily targeted as risk factors for CL±P rather than factors related to a deprived place of residence.

Objetivo. Analizar los efectos de un bajo nivel socioeconómico individual y una zona geográfica desfavorable en la aparición del labio leporino aislado con o sin paladar hendido (LL ± P) en Argentina. Métodos. En este estudio de casos y controles se incluyeron 577 recién nacidos con LL ± P aislado y 13 344 controles sanos nacidos entre 1992 y 2001, de un total de 546 129 nacimientos ocurridos en 39 hospitales de Argentina. Para identificar las zonas geográficas desfavorables se utilizaron datos del Índice de Necesidades Básicas Insatisfechas. Se calculó un índice de nivel socioeconómico para cada participante usando la edad materna, el número de embarazos, el nivel de instrucción bajo del padre y la madre, y el nivel de ocupación bajo del padre. Se usó regresión logística para evaluar los efectos de un bajo nivel socioeconómico y una zona geográfica desfavorable en la ocurrencia de LL ± P. Resultados. Se observó un riesgo levemente mayor de LL ± P en madres con bajo nivel socioeconómico, mientras que una zona geográfica desfavorable no mostró ningún efecto. La ascendencia indígena, las enfermedades agudas maternas y una atención prenatal deficiente fueron factores de riesgo significativos para LL ± P en madres con bajo nivel socioeconómico, después de ajustar las características demográficas de casos y controles mediante análisis de propensión. Conclusiones. Un bajo nivel socioeconómico aumentó levemente el riesgo de LL ± P, pero una zona geográfica desfavorable no mostró ese efecto. No hubo interacción entre un bajo nivel socioeconómico individual y una zona geográfica desfavorable. Los factores relacionados con un bajo nivel socioeconómico individual —inclusive una atención prenatal deficiente, la baja educación de los padres, la falta de información y el estilo de vida— deben abordarse principalmente como factores de riesgo de LL ± P más que los factores relacionados con una zona de residencia desfavorable.

Objetivo. Examinar os efeitos do baixo nível socioeconômico individual e área geográfica em situação de carência na ocorrência de fissura labial isolada com ou sem fissura palatina (FL ± P) na Argentina. Métodos. Estudo de caso-controle que compreendeu 577 recém-nascidos com FL isolada ± P e 13 344 controles saudáveis, nascidos entre 1992 e 2001, de uma população total de 546 129 nascimentos em 39 hospitais na Argentina. Foram usados dados censitários sobre necessidades básicas existentes para estabelecer o grau de carência das áreas geográficas. Foi determinado um índice de nível socioeconômico para cada indivíduo baseado na idade materna, número de gestações, baixa escolaridade materna e paterna e ocupação paterna de baixo nível. Foi realizada uma regressão logística para avaliar os efeitos do baixo nível socioeconômico e área geográfica em situação de carência na ocorrência de FL ± P. Resultados. Observou-se um risco discretamente aumentado de FL ± P em mães com baixo nível socioeconômico, mas nenhum efeito foi verificado quanto à área geográfica em situação de carência. Descendência indígena, doença materna aguda e assistência pré-natal precária foram fatores de risco importantes para FL ± P nas mães com baixo nível socioeconômico, após o uso de escores de propensão para ajustar as características demográficas em casos e controles. Conclusões. O baixo nível socioeconômico individual foi associado a um discreto aumento do risco de FL ± P, mas este efeito não foi observado para área geográfica em situação de carência. Não houve interação entre nível socioeconômico individual e área geográfica em situação de carência. Fatores relacionados ao baixo nível socioeconômico individual, como assistência pré-natal precária, baixa escolaridade dos pais, falta de informação e fatores relacionados aos hábitos de vida, devem ser o foco principal porque eles são os fatores de risco para FL ± P, não fatores relacionados ao domicílio em área carente.

Individual deprivation, regional deprivation, and risk for oral clefts in Argentina / Privación económica individual y regional, y riesgo de hendiduras orofaciales en Argentina / Carência individual, carência regional e risco de fissuras orais na Argentina

ABSTRACT Objective The aim of this study was to analyze the effects of individual low socioeconomic status (SES) and deprived geographical area (GA) on the occurrence of isolated cleft lip with or without cleft palate (CL±P) in Argentina. Methods This case-control study included 577 newborns with isolated CL±P and 13 344 healthy controls, born between 1992 and 2001, from a total population of 546 129 births in 39 hospitals in Argentina. Census data on unsatisfied basic needs were used to establish the degree of geographical area deprivation. An SES index for each individual was established, using maternal age, gravidity, low paternal and maternal education, and low-level paternal occupation. Logistic regression was used to assess the effects of low SES and of deprived GA on CL±P. Results A slightly increased risk of CL±P was observed in mothers with a low SES, while a deprived GA showed no effect. Native ancestry, acute maternal illnesses, and poor prenatal care were significant risk factors for CL±P for the mothers with low SES, after using propensity scores to adjust for the demographic characteristics in cases and controls. Conclusions Low individual SES slightly increased the risk for CL±P, but a deprived GA did not have that effect. There was no interaction between individual SES and deprived GA. Factors related to low individual SES—including poor prenatal care, low parental education, lack of information, and lifestyle factors—should be primarily targeted as risk factors for CL±P rather than factors related to a deprived place of residence.

RESUMEN Objetivo Analizar los efectos de un bajo nivel socioeconómico individual y una zona geográfica desfavorable en la aparición del labio leporino aislado con o sin paladar hendido (LL ± P) en Argentina. Métodos En este estudio de casos y controles se incluyeron 577 recién nacidos con LL ± P aislado y 13 344 controles sanos nacidos entre 1992 y 2001, de un total de 546 129 nacimientos ocurridos en 39 hospitales de Argentina. Para identificar las zonas geográficas desfavorables se utilizaron datos del Índice de Necesidades Básicas Insatisfechas. Se calculó un índice de nivel socioeconómico para cada participante usando la edad materna, el número de embarazos, el nivel de instrucción bajo del padre y la madre, y el nivel de ocupación bajo del padre. Se usó regresión logística para evaluar los efectos de un bajo nivel socioeconómico y una zona geográfica desfavorable en la ocurrencia de LL ± P. Resultados Se observó un riesgo levemente mayor de LL ± P en madres con bajo nivel socioeconómico, mientras que una zona geográfica desfavorable no mostró ningún efecto. La ascendencia indígena, las enfermedades agudas maternas y una atención prenatal deficiente fueron factores de riesgo significativos para LL ± P en madres con bajo nivel socioeconómico, después de ajustar las características demográficas de casos y controles mediante análisis de propensión. Conclusiones Un bajo nivel socioeconómico aumentó levemente el riesgo de LL ± P, pero una zona geográfica desfavorable no mostró ese efecto. No hubo interacción entre un bajo nivel socioeconómico individual y una zona geográfica desfavorable. Los factores relacionados con un bajo nivel socioeconómico individual —inclusive una atención prenatal deficiente, la baja educación de los padres, la falta de información y el estilo de vida— deben abordarse principalmente como factores de riesgo de LL ± P más que los factores relacionados con una zona de residencia desfavorable.

RESUMO Objetivo Examinar os efeitos do baixo nível socioeconômico individual e área geográfica em situação de carência na ocorrência de fissura labial isolada com ou sem fissura palatina (FL ± P) na Argentina. Métodos Estudo de caso-controle que compreendeu 577 recém-nascidos com FL isolada ± P e 13 344 controles saudáveis, nascidos entre 1992 e 2001, de uma população total de 546 129 nascimentos em 39 hospitais na Argentina. Foram usados dados censitários sobre necessidades básicas existentes para estabelecer o grau de carência das áreas geográficas. Foi determinado um índice de nível socioeconômico para cada indivíduo baseado na idade materna, número de gestações, baixa escolaridade materna e paterna e ocupação paterna de baixo nível. Foi realizada uma regressão logística para avaliar os efeitos do baixo nível socioeconômico e área geográfica em situação de carência na ocorrência de FL ± P. Resultados Observou-se um risco discretamente aumentado de FL ± P em mães com baixo nível socioeconômico, mas nenhum efeito foi verificado quanto à área geográfica em situação de carência. Descendência indígena, doença materna aguda e assistência pré-natal precária foram fatores de risco importantes para FL ± P nas mães com baixo nível socioeconômico, após o uso de escores de propensão para ajustar as características demográficas em casos e controles. Conclusões O baixo nível socioeconômico individual foi associado a um discreto aumento do risco de FL ± P, mas este efeito não foi observado para área geográfica em situação de carência. Não houve interação entre nível socioeconômico individual e área geográfica em situação de carência. Fatores relacionados ao baixo nível socioeconômico individual, como assistência pré-natal precária, baixa escolaridade dos pais, falta de informação e fatores relacionados aos hábitos de vida, devem ser o foco principal porque eles são os fatores de risco para FL ± P, não fatores relacionados ao domicílio em área carente.

Descriptive analysis of high birth prevalence rate geographical clusters of congenital anomalies in South America.

BACKGROUND: The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and sociocultural variations throughout the world. In South America (SA), high birth prevalence regions of congenital anomalies have been observed. The aim of this study was to identify, describe, and characterize geographical clusters of congenital anomalies in SA. METHODS: This observational descriptive study is based on clinical epidemiological data registered by the Latin-American Collaborative Study of Congenital Malformations network. Between 1995 and 2012, a total of 25,082 malformed newborns were ascertained from 2,557,424 births at 129 hospitals in SA. The spatial scan statistic was used to determine geographical regions with high BPR of CAs. The BPR was obtained with a Poisson regression model. Odds ratios were estimated for several risk factors inside the geographical clusters. RESULTS: We confirmed the existence of high BPR regions of CAs in SA. Indicators of low socioeconomic conditions, such as a low maternal education, extreme age childbearing, infectious diseases, and medicine use during pregnancy were detected as risk factors inside these regions. Native and African ancestries with high frequency of consanguineous marriages could explain partially these high BPR clusters. CONCLUSION: The recognition of clusters could be a starting point in the identification of susceptibility genes associated with the occurrence of CA in high BPR regions.

Is gravidity 4+ a risk factor for oral clefts? A case-control study in eight South american countries using structural equation modeling.

Background : There is disagreement about the association between cleft lip with or without cleft palate and multigravidity, which could be explained by differences of adjusting for maternal age, Amerindian ancestry, and socioeconomic status. Objective : The aim was to evaluate gravidity 4+ (four or more gestations) as a risk factor for cleft lip with or without cleft palate in South America. Design : We used a matched (1:1) case-control study with structural equation modeling for related causes. Data were obtained from 1,371,575 consecutive newborn infants weighing ≥500 g who were born in the hospitals of the Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC) network between 1982 and 1999. There were a total of 1,271 cases with cleft lip with or without cleft palate (excluding midline and atypical cleft lip with or without cleft palate). A total of 1,227 case-control pairs were obtained, matched by maternal age, newborn gender, and year and place of birth. Potential confounders and intermediary variables were analyzed with structural equation modeling. Results : The crude risk of gravidity 4+ was 1.41 and the 95% confidence interval was 1.14 to 1.61. When applying structural equation modeling, the effect of multigravidity on the risk of cleft lip with or without cleft palate was 1.22 and the 95% confidence interval was 0.91 to 1.39. Conclusions : Multigravid mothers (more than four gestations) showed no greater risk of bearing children who had cleft lip with or without cleft palate than mothers with two or three births. Therefore, the often observed and reported association between multigravidity and oral clefts likely reflects the effect of other risk factors related to low socioeconomic status in South American populations.

GLIA: A reassessment based on novel data on the developing and mature central nervous system.

Several studies on neurobiology have contributed to our understanding of the genesis, survival and death of neurons, unquestionably the stars of the Central Nervous System (CNS). However, they would not be so famous without their close associates: the glial cells. Since novel studies have demonstrated new and important functions for glial cells, they are beginning to gain significant importance in brain research to allow us to reinterpret long known functions on the basis of new concepts. Here, we review recent progress in our understanding of the role of glial cells in the biology of tissue development and maturation.