Biochemistry, Genetics and Molecular Biology, Genetics, Microbiology, Infectious Diseases
34
Scopus Publications
Scopus Publications
Profile of Multidrug-Resistant Bacteria in Intensive Care Units of a Maternal and Child Hospital in Rio de Janeiro, Brazil Lucas Meneses de Oliveira Villar, Natalie Del-Vecchio Lages Costa, Danielle Bonotto Cabral Reis, Adriana Teixeira Reis, Leticia Linhares Braga, Fabíola Cristina de Oliveira Kegele, Maria da Conceição Borges Lopes, Maria Francisca da Silva Neta Soares, Maria Elisabeth Lopes Moreira, Natália Chantal Magalhães da Silva, Leonardo Henrique Ferreira Gomes, Letícia da Cunha Guida Antibiotics, 2025 Background/Objectives: Epidemiological surveillance of healthcare-associated infections (HAIs) and multidrug-resistant (MDR) bacteria is a key responsibility of hospital infection control committees (HICC). Active surveillance swabs facilitate the early detection of colonized patients; helping to prevent MDR pathogen transmission in intensive care units. This study aimed to describe antimicrobial resistance profiles of bacterial isolates from clinical samples in neonatal and pediatric intensive care units. Methods: A retrospective cross-sectional study was conducted at a maternal and child hospital in Rio de Janeiro, Brazil including patients aged 0–18 years admitted to neonatal (NICU), surgical (SICU), and pediatric (PICU) intensive care units between January and December 2023. A total of 286 positive cultures were analyzed from different sample types including blood, urine, tracheal aspirates, cerebrospinal fluid (CSF), and catheter tips as well as screening swabs (nasal and rectal) for colonization surveillance. Bacterial isolates were identified and tested for antimicrobial susceptibility following BrCAST (Brazilian Committee on Antimicrobial Susceptibility Testing) guidelines. Results: Of the 286 cultures, 146 (51%) originated from the NICU, 70 (24%) from the SICU, and 70 (24%) from the PICU. Coagulase-negative staphylococci (CoNS) predominated in blood cultures, especially among neonates, while MRSA was found in all nasal swabs. Among the Gram-negative bacteria; Klebsiella pneumoniae and Pseudomonas aeruginosa were the most frequent isolates, with 30–50% resistant to third-generation cephalosporins or carbapenems. ESBL-producing organisms were found in 40% of rectal swabs. Conclusions: The predominance of CoNS in neonatal ICUs and high resistance rates among Gram-negative bacteria highlight the urgent need for continuous microbiological surveillance and antimicrobial stewardship in vulnerable pediatric populations.
FOXP2 Expression and Oral Feeding Success in Preterm Infants: Sex 2 Differences Leonardo Henrique Ferreira Gomes, Andressa Brito Marques, Isabel Cristina de Meireles Dias, Daniela Prado Cunha, Hellen Porto Pimenta, Letícia da Cunha Guida, Sabrina Lopes Lucena, Adriana Duarte Rocha Genes, 2025 Background: The FOXP2 gene, crucial for speech and motor functions, exhibits sex-specific expression differences. In premature infants, elevated FOXP2 expression, particularly in females, correlates with improved oral feeding readiness, indicating the potential for enhancing neonatal care. Objective: This study investigates FOXP2 gene expression in premature newborns across five feeding stages using salivary RNA, focusing on sex differences and their impact on oral feeding readiness to refine neonatal clinical protocols. Methods: FOXP2 expression was analyzed using RT-qPCR and the ΔΔCt method across five feeding stages in 45 premature newborns using saliva-derived RNA (n = 225). Results: FOXP2 expression increased significantly through feeding stages, especially in full oral feeding. Female infants showed consistently higher expression levels than males, with 58% higher expression by stage 5. Significant sex differences were apparent from stage 2. Conclusions: FOXP2 expression impacts neuromuscular coordination and feeding readiness in preterm infants. The sex differences suggest that FOXP2 could serve as a non-invasive biomarker for predicting oral feeding readiness, potentially improving clinical outcomes. Perspectives: FOXP2 gene expression correlates with better oral feeding readiness in premature infants and may serve as a non-invasive biomarker to improve neonatal care. The study could enhance neonatal care, leading to improved outcomes and reduced hospital stays for preterm infants.
Characterization of mycobacteria isolated from the Brazilian Atlantic Forest: a public health and bioprospection perspective Leandro Santiago Emmerick, Marcos Gustavo Araujo Schwarz, Paloma Rezende Corrêa, Sindy Licette Piñero, Leonardo Henrique Ferreira Gomes, Ana Maria Mazotto Almeida, Richard Hemmi Valente, Wim Maurits Sylvain Degrave, Leila Mendonça-Lima Frontiers in Microbiology, 2025 The Mycobacterium genus remains highly relevant today due to the rising incidence of tuberculosis and opportunistic infections caused by environmental mycobacteria. While much is known about M. tuberculosis, M. leprae and M. bovis, studies focusing on environmental mycobacteria remain limited. These microorganisms are globally distributed and have been identified in diverse biomes, including the Atlantic Forest. This study aims to provide a characterization of four mycobacterial strains isolated from the Atlantic Forest, assessing their metabolic capabilities and biotechnological potential. We investigated the presence of cellulases and proteases and conducted an initial profiling of secreted proteins. Furthermore, the examination of shared antigens and infection kinetics within macrophages offered insights into the ecological and pathogenic potential of these isolates. From a public health perspective, antigenic similarities between these environmental microorganisms and the BCG vaccine strain may influence the efficacy of BCG in protecting against diseases such as tuberculosis. Continued research on these and other environmental isolates, particularly within Brazil’s highly biodiverse ecosystems, holds promise for advancing scientific knowledge and contributing to human health.
Clinical and Cytogenetic Impact of Maternal Balanced Double Translocation: A Familial Case of 15q11.2 Microduplication and Microdeletion Syndromes with Genetic Counselling Implications Daniela Koeller R. Vieira, Ingrid Bendas Feres Lima, Carla Rosenberg, Carlos Roberto da Fonseca, Leonardo Henrique Ferreira Gomes, Letícia da Cunha Guida, Patrícia Camacho Mazzonetto, Juan Llerena, Elenice Ferreira Bastos Genes, 2024 Background: Balanced chromosomal translocations occur in approximately 0.16 to 0.20% of live births. While most carriers are phenotypically normal, they are at risk of generating unbalanced gametes during meiosis, leading to genetic anomalies such as aneuploidies, deletions, duplications, and gene disruptions. These anomalies can result in spontaneous abortions or congenital anomalies, including neurodevelopmental disorders. Complex chromosomal rearrangements (CCRs) involving more than two chromosomes are rare but further increase the probability of producing unbalanced gametes. Neurodevelopmental disorders such as Angelman syndrome (AS) and duplication 15q11q13 syndrome (Dup15q) are associated with such chromosomal abnormalities. Methods: This study describes a family with a de novo maternal balanced double translocation involving chromosomes 13, 19, and 15, resulting in two offspring with unbalanced chromosomal abnormalities. Cytogenetic evaluations were performed using GTG banding, fluorescence in situ hybridization (FISH), and low-pass whole-genome sequencing (LP-WGS). Methylation analysis was conducted using methylation-sensitive high-resolution melting (MS-HRM) to diagnose Angelman syndrome. Results: The cytogenetic and molecular analyses identified an 8.9 Mb duplication in 15q11.2q13.3 in one child, and an 8.9 Mb deletion in the same region in the second child. Both abnormalities affected critical neurodevelopmental genes, such as SNRPN. FISH and MS-HRM confirmed the chromosomal imbalances and the diagnosis of Angelman syndrome in the second child. The maternal balanced translocation was found to be cryptic, contributing to the complex inheritance pattern. Conclusion: This case highlights the importance of using multiple genetic platforms to uncover complex chromosomal rearrangements and their impact on neurodevelopmental disorders. The findings underscore the need for thorough genetic counseling, especially in families with such rare chromosomal alterations, to manage reproductive outcomes and neurodevelopmental risks.
Investigating the correlation between genotype and phenotype in Prader-Willi syndrome: a study of 45 cases from Brazil Hiago Azevedo Cintra, Danielle Nascimento Rocha, Ana Carolina Carioca da Costa, Latife Salomão Tyszler, Silvia Freitas, Leonardo Abreu de Araujo, Lisanne Incoutto Crozoe, Luísa Ribeiro de Paula, Patricia Santana Correia, Leonardo Henrique Ferreira Gomes, Letícia da Cunha Guida Orphanet Journal of Rare Diseases, 2024 Background Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in PWS is crucial for improved genetic counseling and prognosis. In this study, we aimed to investigate the correlation between genotype and phenotype in 45 PWS patients who previously underwent methylation-sensitive high-resolution melting (MS-HRM) for diagnosis. Results We employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and Sanger sequencing, along with collecting phenotypic data from the patients for comparison. Among the 45 patients, 29 (64%) exhibited a deletion of 15q11-q13, while the remaining 16 (36%) had uniparental disomy. No statistically significant differences were found in the main signs and symptoms of PWS. However, three clinical features showed significant differences between the groups. Deletion patients had a higher prevalence of myopia than those with uniparental disomy, as well as obstructive sleep apnea and an unusual skill with puzzles. Conclusions The diagnostic tests (MS-HRM, MS-MLPA, and Sanger sequencing) yielded positive results, supporting their applicability in PWS diagnosis. The study’s findings indicate a general similarity in the genotype-phenotype correlation across genetic subtypes of PWS.
Validation of Gene Expression Patterns for Oral Feeding Readiness: Transcriptional Analysis of Set of Genes in Neonatal Salivary Samples Leonardo Henrique Ferreira Gomes, Andressa Brito Marques, Isabel Cristina de Meireles Dias, Sanny Cerqueira de O. Gabeira, Tamara Rosa Barcelos, Mariana de Oliveira Guimarães, Igor Ribeiro Ferreira, Letícia Cunha Guida, Sabrina Lopes Lucena, Adriana Duarte Rocha Genes, 2024 Background: Neonatal health assessment is crucial for detecting and intervening in various disorders. Traditional gene expression analysis methods often require invasive procedures during sample collection, which may not be feasible or ideal for preterm infants. In recent years, saliva has emerged as a promising noninvasive biofluid for assessing gene expression. Another trend that has been growing is the use of “omics” technologies such as transcriptomics in the analysis of gene expression. The costs for carrying out these analyses and the difficulty of analysis make the detection of candidate genes necessary. These genes act as biomarkers for the maturation stages of the oral feeding issue. Methodology: Salivary samples (n = 225) were prospectively collected from 45 preterm (<34 gestational age) infants from five predefined feeding stages and submitted to RT-qPCR. A better description of the targeted genes and results from RT-qPCR analyses were included. The six genes previously identified as predictive of feeding success were tested. The genes are AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1, along with two reference genes: GAPDH and 18S. RT-qPCR amplification enabled the analysis of the gene expression of AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 in neonatal saliva. Expression results were correlated with the feeding status during sample collection. Conclusions: In summary, the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding and the development of premature infants. Understanding the influence of these genes can provide valuable insights for improving nutritional care and support the development of these vulnerable babies. Evidence suggests that saliva-based gene expression analysis in newborns holds great promise for early detection and monitoring of disease and understanding developmental processes. More research and standardization of protocols are needed to fully explore the potential of saliva as a noninvasive biomarker in neonatal care.
The cost of genetic diagnosis of suspected hereditary pediatric cataracts with whole-exome sequencing from a middle-income country perspective: a mixed costing analysis Luiza M. Neves, Márcia Pinto, Olivia A. Zin, Daniela P. Cunha, Bruna N. S. Agonigi, Fabiana L. Motta, Leonardo H. F. Gomes, Dafne D. G. Horovitz, Daltro C. Almeida, Jocieli Malacarne, Leticia Guida, Andressa Braga, Adriana Bastos Carvalho, Eduardo Pereira, Ana Paula S. Rodrigues, Juliana M. F. Sallum, Andrea A. Zin, Zilton F. M. Vasconcelos Journal of Community Genetics, 2024 Up to 25% of pediatric cataract cases are inherited. There is sparse information in the literature regarding the cost of whole-exome sequencing (WES) for suspected hereditary pediatric cataracts. Molecular diagnosis of suspected hereditary pediatric cataracts is important for comprehensive genetic counseling. We performed a partial economic evaluation with a mixed costing analysis, using reimbursement data and microcosting approach with a bottom-up technique to estimate the cost of using WES for genetic diagnosis of suspected hereditary pediatric cataracts from the perspective of the Brazilian governmental health care system. One hundred and ten participants from twenty-nine families in Rio de Janeiro (RJ) were included. Costs of consumables, staff and equipment were calculated. Two scenarios were created: (1) The reference scenario included patients from RJ with suspected hereditary pediatric cataracts plus two family members. (2) The alternative scenario considered other genetic diseases, resulting in 5,280 exams per month. Sensitivity analysis was also performed. In the reference scenario, the total cost per exam was 700.09 United States dollars (USD), and in the alternative scenario, the total cost was 559.23 USD. The cost of WES alone was 527.85 USD in the reference scenario and 386.98 USD in the alternative scenario. Sensitivity analysis revealed that the largest costs were associated with consumables in both scenarios. Economic evaluations can help inform policy decisions, especially in middle-income countries such as Brazil.
Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling Tamiris Azamor, Daniela Prado Cunha, Keyla Silva Nobre Pires, Eloiza Lopes Lira Tanabe, Juliana Gil Melgaço, Andréa Marques Vieira da Silva, Marcelo Ribeiro-Alves, Thyago Leal Calvo, Luciana Neves Tubarão, Jane da Silva, Camilla Bayma Fernandes, Alessandro Fonseca de Souza, Amanda Torrentes de Carvalho, Elyzabeth Avvad-Portari, Letícia da Cunha Guida, Leonardo Gomes, Maria Elisabeth Lopes Moreira, Ana Paula Dinis Ano Bom, Patrícia Cristina da Costa Neves, Sotiris Missailidis, Zilton Vasconcelos, Alexandre Urban Borbely, Milton Ozório Moraes Heliyon, 2024 Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4 . Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1 , 3 , and 4 , whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.
Establishing a Standardized DNA Extraction Method Using NaCl from Oral Mucosa Cells for Its Application in Imprinting Diseases Such as Prader–Willi and Angelman Syndromes: A Preliminary Investigation Letícia Lopes Cabral Guimarães da Fonseca, Danielle Nascimento Rocha, Hiago Azevedo Cintra, Luiza Loureiro de Araújo, Gabrielle Leal Monteiro dos Santos, Leonardo Lima de Faria, Margarida dos Santos Salú, Silvia Helena dos Santos Leite, Adriana Duarte Rocha, Maria da Conceição Borges Lopes, Igor Ribeiro Ferreira, Leonardo Henrique Ferreira Gomes, Letícia Cunha Guida Genes, 2024 Background: Diagnosing imprinting defects in neonates and young children presents challenges, often necessitating molecular analysis for a conclusive diagnosis. The isolation of genetic material from oral swabs becomes crucial, especially in settings where blood sample collection is impractical or for vulnerable populations like newborns, who possess limited blood volumes and are often too fragile for invasive procedures. Oral swab samples emerge as an excellent source of DNA, effectively overcoming obstacles associated with rare diseases. Methods: In our study, we specifically addressed the determination of the quality and quantity of DNA extracted from oral swab samples using NaCl procedures. Results: We compared these results with extractions performed using a commercial kit. Subsequently, the obtained material underwent MS–HRM analysis for loci associated with imprinting diseases such as Prader–Willi and Angelman syndromes. Conclusions: Our study emphasizes the significance of oral swab samples as a reliable source for obtaining DNA for MS–HRM analysis. NaCl extraction stands out as a practical and cost-effective method for genetic studies, contributing to a molecular diagnosis that proves particularly beneficial for patients facing delays in characterization, ultimately influencing their treatment.
Real-time PCR in the diagnosis of congenital toxoplasmosis Bianca Balzano De La Fuente Villar, Leonardo Henrique Ferreira Gomes, Elyzabeth Avvad Portari, Carla Nasser Patrocinio Ramos, Danielle Nascimento Rocha, José Paulo Pereira, Elizabeth de Souza Neves, Letícia da Cunha Guida Brazilian Journal of Infectious Diseases, 2023
Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1 Tamiris Azamor, Daniela Prado Cunha, Andréa Marques Vieira da Silva, Ohanna Cavalcanti de Lima Bezerra, Marcelo Ribeiro-Alves, Thyago Leal Calvo, Fernanda de Souza Gomes Kehdy, Fernanda Saloum de Neves Manta, Thiago Gomes de Toledo Pinto, Laís Pereira Ferreira, Elyzabeth Avvad Portari, Letícia da Cunha Guida, Leonardo Gomes, Maria Elisabeth Lopes Moreira, Elizeu Fagundes de Carvalho, Cynthia Chester Cardoso, Marcelo Muller, Ana Paula Dinis Ano Bom, Patrícia Cristina da Costa Neves, Zilton Vasconcelos, Milton Ozório Moraes Frontiers in Immunology, 2021
Novel mutation in crybb3 causing pediatric cataract and microphthalmia Olivia A. Zin, Luiza M. Neves, Fabiana L. Motta, Dafne D. G. Horovitz, Leticia Guida, Leonardo H. F. Gomes, Daniela P. Cunha, Ana Paula S. Rodrigues, Andrea A. Zin, Juliana M. F. Sallum, Zilton F. M. Vasconcelos Genes, 2021
Whole-exome sequencing reveals insights into genetic susceptibility to congenital zika syndrome Victor Borda, Ronaldo da Silva Francisco Junior, Joseane B. Carvalho, Guilherme L. Morais, Átila Duque Rossi, Paula Pezzuto, Girlene S. Azevedo, Bruno L. Schamber-Reis, Elyzabeth A. Portari, Adriana Melo, Maria Elisabeth L. Moreira, Letícia C. Guida, Daniela P. Cunha, Leonardo Gomes, Zilton F. M. Vasconcelos, Fabio R. Faucz, Amilcar Tanuri, Constantine A. Stratakis, Renato S. Aguiar, Cynthia Chester Cardoso, Ana Tereza Ribeiro de Vasconcelos Plos Neglected Tropical Diseases, 2021
Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome Sara Lovisa, Eliot Fletcher-Sananikone, Hikaru Sugimoto, Janine Hensel, Sharmistha Lahiri, Alexandre Hertig, Gangadhar Taduri, Erica Lawson, Rajan Dewar, Ignacio Revuelta, Noritoshi Kato, Chang-Jiun Wu, Roland L. Bassett, Nagireddy Putluri, Michael Zeisberg, Elisabeth M. Zeisberg, Valerie S. LeBleu, Raghu Kalluri Science Signaling, 2020
P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance Mônica Caroline Oliveira Campos, Denise Barçante Castro-Pinto, Grazielle Alves Ribeiro, Márcia Moreira Berredo-Pinho, Leonardo Henrique Ferreira Gomes, Myrtes Santos da Silva Bellieny, Carla Marins Goulart, Áurea Echevarria, Leonor Laura Leon Parasitology Research, 2013
