Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly.

Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case-control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.

The crucial role of the partner in the incidence of cases of congenital syphilis in the state of Sergipe: an analysis in 17 years / O papel crucial do parceiro na incidência dos casos de sífilis congênita no estado de Sergipe: uma análise em 17 anos

Introduction: Congenital syphilis is a highly preventable infectious disease. The relevance of the partner in the transmission of the disease is undeniable, and the underestimation of its treatment is a great risk with serious fetal consequences. Objective: The aim of this study was to analyze the partner's contribution to the inadequate treatment of pregnant women and the incidence of cases of congenital syphilis in Sergipe between 2005 and 2022. Methods: A cross-sectional, retrospective, and descriptive study was carried out through the collection of reported cases of congenital syphilis from the Notifiable Diseases Information System (SINAN). Results: There was a considerable increase in the number of reported cases of congenital syphilis in Sergipe in the past 17 years, with a predominance of untreated partners (61.5%) over treated ones (14.9%), excluding the 23.6% who had this information ignored. The variations presented from 2018 onwards stand out, resulting from the softening implemented in the notification of partner data, with an average of 23.7% of ignored information. Consequently, the diagnosis of recent congenital syphilis was found in 83.7% of newborns whose parents were not treated, in addition to 50% of cases of late infection and the vast majority of cases of stillbirths/abortion (92.6%) and deaths from the disease (78.8%). Furthermore, the non-inclusion of the partner in prenatal care (83%) contributed mainly to delays in the diagnosis of maternal syphilis, with 90.1% during delivery/curettage, 76.7% after delivery, and 77.2% of them not even identified with the disease. Conclusion: In addition to the increase in cases of congenital syphilis, there was a predominance of untreated partners, coinciding with changes in the notification criteria in 2018, which contributed to most cases of delay in maternal diagnosis, reinfection, and vertical transmission. Thus, the partner's approach is essential to guarantee the treatment and interruption of the transmission of the disease

Introdução: A sífilis congênita é uma doença infectocontagiosa altamente prevenível. A relevância do parceiro na transmissão da doença é inegável, sendo a subestimação do seu tratamento um grande risco, com graves consequências fetais. Objetivo: Analisar a contribuição do parceiro na inadequação do tratamento da gestante e na incidência dos casos de sífilis congênita em Sergipe entre 2005 e 2022. Métodos: Realizou-se um estudo transversal, retrospectivo e descritivo, através da coleta de casos notificados de sífilis congênita do Sistema de Informação de Agravos de Notificação (SINAN). Resultados: Observou-se um aumento considerável do número de casos notificados de sífilis congênita em Sergipe nos últimos 17 anos, com o predomínio de parceiros não tratados (61,5%) em relação aos tratados (14,9%), descontando-se os 23,6% que tiveram essa informação ignorada. Destacam-se as variações apresentadas a partir de 2018, decorrentes da amenização implementada na notificação dos dados do parceiro, com uma média de 23,7% de informações ignoradas. Consequentemente, o diagnóstico de sífilis congênita recente foi encontrado em 83,7% dos recém-nascidos cujos pais não foram tratados, além de 50% dos casos de infecção tardia e a maioria dos casos de natimortos/aborto (92,6%) e óbitos pelo agravo (78,8%). Outrossim, a não inclusão do parceiro na assistência pré-natal (83%) contribuiu majoritariamente nos atrasos no diagnóstico da sífilis materna, sendo 90,1% no parto/curetagem, 76,7% após o parto, além de 77,2% delas que nem mesmo foram identificadas com a doença. Conclusão: Além do aumento de casos de sífilis congênita, houve predomínio de parceiros não tratados, coincidindo com as mudanças nos critérios de notificação em 2018, o que contribuiu para a maioria dos casos de atraso no diagnóstico materno, reinfecção e transmissão vertical. Assim, a abordagem do parceiro é imprescindível para garantia do tratamento e da interrupção da transmissão da doença

USE OF OFF-LABEL MEDICATIONS IN A NEONATAL INTENSIVE CARE UNIT.

OBJECTIVE: This paper aims to analyze the use of off label (OL) medicines, according to the National Regulatory Agency, in a neonatal intensive care unit of a high-risk maternity hospital in Northeast Brazil. METHODS: A cross-sectional study was carried out, using a convenience sample of newborns that used mechanical ventilation at the Intensive Care Unit. As a reference, OL medications were considered for those without an approval for newborn usage by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA) and by the Food and Drugs Administration (FDA). RESULTS: The sample consisted of 158 newborns, 58.3% male, 87.7% premature, and 70.2% of low or very low birth weight. According to ANVISA, 440 out of the 1,167 prescriptions analyzed were OL, with 98.1% of newborns exposed to at least one of these drugs. According to the FDA, 484 prescriptions were OL, with 75.8% of newborns exposed to at least one of them. Anti-infectives were the most prescribed OL medications. Neonates who presented respiratory failure and pneumonia used these drugs more often; and there was no relation between their use and the number of deaths. CONCLUSIONS: Nearly all newborns at the Intensive Care Units, mainly preterm infants, are exposed to at least one off-label (OL) medication during hospital stay, according to the national and international regulatory agencies. No association was found between off-label prescriptions and the frequency of complications or neonatal deaths.

Use of off-label medications in a neonatal intensive care unit / Uso de medicamentos off-label em unidade de terapia intensiva neonatal

ABSTRACT Objective: This paper aims to analyze the use of off label (OL) medicines, according to the National Regulatory Agency, in a neonatal intensive care unit of a high-risk maternity hospital in Northeast Brazil. Methods: A cross-sectional study was carried out, using a convenience sample of newborns that used mechanical ventilation at the Intensive Care Unit. As a reference, OL medications were considered for those without an approval for newborn usage by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA) and by the Food and Drugs Administration (FDA). Results: The sample consisted of 158 newborns, 58.3% male, 87.7% premature, and 70.2% of low or very low birth weight. According to ANVISA, 440 out of the 1,167 prescriptions analyzed were OL, with 98.1% of newborns exposed to at least one of these drugs. According to the FDA, 484 prescriptions were OL, with 75.8% of newborns exposed to at least one of them. Anti-infectives were the most prescribed OL medications. Neonates who presented respiratory failure and pneumonia used these drugs more often; and there was no relation between their use and the number of deaths. Conclusions: Nearly all newborns at the Intensive Care Units, mainly preterm infants, are exposed to at least one off-label (OL) medication during hospital stay, according to the national and international regulatory agencies. No association was found between off-label prescriptions and the frequency of complications or neonatal deaths.

RESUMO Objetivo: Analisar o uso de medicamentos off-label (OL), segundo a agência reguladora nacional, em unidade de terapia intensiva neonatal de uma maternidade de alto risco em Aracaju. Métodos: Foi realizado um estudo transversal, utilizando amostra de conveniência de recém-nascidos (RN) da Unidade Intensiva, que fizeram uso de ventilação mecânica. Consideramos OL o medicamento que não era liberado para uso em RN nos bulários eletrônicos da Agência Nacional de Vigilância Sanitária (ANVISA) e da U.S. Food and Drug Administration (FDA). Resultados: A amostra consistiu de 158 neonatos, sendo 58,3% do sexo masculino, 87,7% prematuros e 70,2% com baixo ou muito baixo peso. De acordo com a ANVISA, das 1.167 prescrições analisadas, 440 foram OL, com 98,1% dos RN expostos a pelo menos um desses medicamentos. Já para a FDA, 484 prescrições foram OL, com 75,8% dos neonatos expostos a pelo menos um deles. As medicações OL mais prescritas foram os anti-infecciosos. Neonatos que apresentaram insuficiência respiratória e pneumonia fizeram mais uso deles e não houve relação entre o seu uso e o número de óbitos. Conclusões: Quase todos os RN internados, principalmente os prematuros, foram expostos a pelo menos um medicamento OL, de acordo com a agência reguladora nacional e internacional, durante a internação. Entretanto, isso não teve relação com a frequência de complicações nem de óbitos neonatais.

Sociodemographic and obstetric factors related to low birth weight in the context of early pregnancy / Fatores sociodemográficos e obstétricos relacionados ao baixo peso em recém-nascidos no contexto da gravidez precoce

Abstract Objectives: to analyze sociodemographic and obstetric factors that may influence the occurrence of low birth weight in the context of early pregnancy. Methods: the sample consisted of 232 pregnant teenagers, aged 10-19 years old, were assisted at a public maternity hospital in Aracaju-SE during the period of August 2012 to July 2016. The data collection was conducted through a structured questionnaire. Results: low birth weight was observed in 41.38% of the newborns and there was a statistical association between the educational level and the marital status with the occurrence of low birth weight in newborns among teenage mothers, with p=0.0286 and p=0.0247, respectively. Conclusions: the socioeconomic factors may contribute to the occurrence of low birth weight in newborns of teenage mothers and teenage pregnancy at this age represents a serious public health problem.

Resumo Objetivos: analisar os fatores sociodemográficos e obstétricos que podem influenciar na ocorrência do baixo peso ao nascer no contexto da gravidez precoce. Métodos: amostra constou de 232 adolescentes grávidas, na faixa etária de 10 a 19 anos, atendidas em uma maternidade pública de Aracaju-SE, Brasil, durante o período de agosto de 2012 a julho de 2016. A coleta de dados foi realizada através de um questionário estruturado. Resultados: observou-se baixo peso em 41,38% dos recém-nascidos e que o nível de escolaridade e o tipo de vínculo com o parceiro tiveram relevância estatística para a ocorrência do baixo peso em recém-nascidos de mães adolescentes, com p=0,0286 e p=0,0247, respectivamente. Conclusões: os fatores socioeconômicos podem contribuir para a ocorrência de baixo peso em recém-nascidos de mães adolescentese que a gravidez nesta faixa etária constitui grave problema de saúde pública de natureza multifatorial.

Pulmonary involvement in human visceral leishmaniasis: Clinical and tomographic evaluation.

Visceral leishmaniasis (VL) is a severe, systemic and potentially lethal parasitosis. The lung, like any other organ, can be affected in VL, and interstitial pneumonitis has been described in past decades. This research aimed to bring more recent knowledge about respiratory impairment in VL, characterizing pulmonary involvement through clinical, radiographic and tomographic evaluation. This is an observational, cross-sectional study that underwent clinical evaluation, radiography and high-resolution computed tomography of the chest in patients admitted with the diagnosis of VL in a university service in Northeast Brazil, from January 2015 to July 2018. The sample consisted of 42 patients. Computed tomography was considered abnormal in 59% of patients. Images compatible with pulmonary interstitial involvement were predominant (50%). The most observed respiratory symptom was cough (33.3%), followed by tachypnea (14.1%). Chest radiography was altered in only four patients. VL is a disease characterized by systemic involvement and broad spectrum of clinical manifestations. The respiratory symptoms and tomographic alterations found show that the involvement of respiratory system in VL deserves attention because it is more common than previously thought. Chest X-ray may not reveal this impairment.

Publisher Correction: Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.

The original PDF version of this Article contained errors in the spelling of Luiz Carlos Caires-Júnior, Uirá Souto Melo, Bruno Henrique Silva Araujo, Alessandra Soares-Schanoski, Murilo Sena Amaral, Kayque Alves Telles-Silva, Vanessa van der Linden, Helio van der Linden, João Ricardo Mendes de Oliveira, Nivia Maria Rodrigues Arrais, Joanna Goes Castro Meira, Ana Jovina Barreto Bispo, Esper Abrão Cavalheiro, and Robert Andreata-Santos, which were incorrectly given as Luiz Carlos de Caires Jr., UiráSouto Melo, Bruno Silva Henrique Araujo, Alessandra Soares Schanoski, MuriloSena Amaral, Kayque Telles Alves Silva, Vanessa Van der Linden, Helio Van der Linden, João Mendes Ricardo de Oliveira, Nivia Rodrigues Maria Arrais, Joanna Castro Goes Meira, Ana JovinaBarreto Bispo, EsperAbrão Cavalheiro, and Robert Andreata Santos. Furthermore, in both the PDF and HTML versions of the Article, the top panel of Fig. 3e was incorrectly labeled '10608-1' and should have been '10608-4', and financial support from CAPES and DECIT-MS was inadvertently omitted from the Acknowledgements section. These errors have now been corrected in both the PDF and HTML versions of the Article.

Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.

Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare by RNA-Seq the NPCs derived from CZS-affected and CZS-unaffected twins. Prior to Zika virus (ZIKV) infection the NPCs from CZS babies show a significantly different gene expression signature of mTOR and Wnt pathway regulators, key to a neurodevelopmental program. Following ZIKV in vitro infection, cells from affected individuals have significantly higher ZIKV replication and reduced cell growth. Whole-exome analysis in 18 affected CZS babies as compared to 5 unaffected twins and 609 controls excludes a monogenic model to explain resistance or increased susceptibility to CZS development. Overall, our results indicate that CZS is not a stochastic event and depends on NPC intrinsic susceptibility, possibly related to oligogenic and/or epigenetic mechanisms.

Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells

Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare by RNA-Seq the NPCs derived from CZS-affected and CZS-unaffected twins. Prior to Zika virus (ZIKV) infection the NPCs from CZS babies show a significantly different gene expression signature of mTOR and Wnt pathway regulators, key to a neurodevelopmental program. Following ZIKV in vitro infection, cells from affected individuals have significantly higher ZIKV replication and reduced cell growth. Whole-exome analysis in 18 affected CZS babies as compared to 5 unaffected twins and 609 controls excludes a monogenic model to explain resistance or increased susceptibility to CZS development. Overall, our results indicate that CZS is not a stochastic event and depends on NPC intrinsic susceptibility, possibly related to oligogenic and/or epigenetic mechanisms.