Whole genome sequencing as a first-tier diagnostic test for infants in neonatal intensive care units: A pilot study in Brazil.

In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first-tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X-linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting.

Low-pass whole genome sequencing is a reliable and cost-effective approach for copy number variant analysis in the clinical setting.

INTRODUCTION: Next generation sequencing technology has greatly reduced the cost and time required for sequencing a genome. An approach that is rapidly being adopted as an alternative method for CNV analysis is the low-pass whole genome sequencing (LP-WGS). Here, we evaluated the performance of LP-WGS to detect copy number variants (CNVs) in clinical cytogenetics. MATERIALS AND METHODS: DNA samples with known CNVs detected by chromosomal microarray analyses (CMA) were selected for comparison and used as positive controls; our panel included 44 DNA samples (12 prenatal and 32 postnatal), comprising a total of 55 chromosome imbalances. The selected cases were chosen to provide a wide range of clinically relevant CNVs, the vast majority being associated with intellectual disability or recognizable syndromes. The chromosome imbalances ranged in size from 75 kb to 90.3 Mb, including aneuploidies and two cases of mosaicism. RESULTS: All CNVs were successfully detected by LP-WGS, showing a high level of consistency and robust performance of the sequencing method. Notably, the size of chromosome imbalances detected by CMA and LP-WGS were compatible between the two different platforms, which indicates that the resolution and sensitivity of the LP-WGS approach are at least similar to those provided by CMA. DISCUSSION: Our data show the potential use of LP-WGS to detect CNVs in clinical diagnosis and confirm the method as an alternative for chromosome imbalances detection. The diagnostic effectiveness and feasibility of LP-WGS, in this technical validation study, were evidenced by a clinically representative dataset of CNVs that allowed a systematic assessment of the detection power and the accuracy of the sequencing approach. Further, since the software used in this study is commercially available, the method can easily be tested and implemented in a routine diagnostic setting.

A Benchmark of In-House Homologous Recombination Repair Deficiency Testing Solutions for High-Grade Serous Ovarian Cancer Diagnosis.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients' treatment options and has been progressively incorporated into diagnostic laboratories. Here, we assessed the performance of an in-house HRD testing system deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx® (HRD Focus Panel)) with the reference assay from Myriad MyChoice® (CDx). A total of 85 ovarian cancer samples were subject to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R = 0.87, p-value = 3.39 × 10-19). The comparison of the assigned HRD status to the reference Myriad's test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA's test, while AmoyDx's test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data shows that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, making it an ideal alternative to offer to a broader number of patients while maintaining high-quality standards at more accessible price tiers.

[Nutritional adequacy and food waste in Early Childhood Education Centers]. / Adequação nutricional e desperdício de alimentos em Centros de Educação Infantil.

Analyzing quantitative and qualitative aspects of school meals represents the initial stage to ensure that the National School Food Program (PNAE) is an effective space for the promotion of healthy eating habits and establishing individual rights. The objective of this study was to evaluate the nutritional adequacy of meals served and consumed, as well as quantifying food waste in Child Daycare Centers in Maceió, in the state of Alagoas. All meals served and consumed by 359 children (aged 17 to 63 months) were analyzed by the direct weighing method for three non-consecutive days in all institutions. Food waste was determined by the leftover factor and the nutritional value of meals served and consumed was compared to the PNAE reference values regarding energy, carbohydrates, protein, lipids, vitamins A and C, iron, calcium, zinc, magnesium and fiber. Of the 85 meals/preparations featured on the menu, 58 (68%) revealed a high leftover percentage; in excess of 10%. The meals served and consumed met approximately 50% of the recommended energy and macronutrient values. The difference between the averages of the nutrients offered and consumed was statistically significant (p < 0.05) for fiber, vitamin A, vitamin C, calcium, iron and zinc.

Analisar aspectos quantitativos e qualitativos da alimentação escolar constitui-se de etapa primordial para fazer do Programa Nacional de Alimentação Escolar (PNAE) um espaço efetivo para a promoção da alimentação saudável e formação de sujeitos de direitos. O objetivo deste estudo foi avaliar a adequação nutricional das refeições servidas e consumidas e quantificar o desperdício de alimentos em Centros de Educação Infantil de Maceió/AL. Foram analisadas por três dias não consecutivos, pelo método de pesagem direta, as refeições de 359 crianças (17 e 63 meses). O desperdício de alimentos foi determinado pelo índice de resto-ingestão e o valor nutricional das refeições servidas e consumidas foram comparadas com os valores de referência do PNAE para energia, carboidrato, proteína, lipídio, vitaminas A e C, ferro, cálcio, zinco, magnésio e fibra. Dos 85 alimentos/preparações presentes no cardápio, 58 (68%) apresentaram percentual de resto-ingestão, superior a 10%. As refeições servidas e consumidas atenderam aproximadamente 50% do recomendado para energia e macronutrientes. A diferença entre as médias dos nutrientes ofertados e consumidos foi estatisticamente significante (p < 0,05) para fibra, vitamina A, vitamina C, cálcio, ferro e zinco.

Adequação nutricional e desperdício de alimentos em Centros de Educação Infantil / Nutritional adequacy and food waste in Early Childhood Education Centers

Resumo Analisar aspectos quantitativos e qualitativos da alimentação escolar constitui-se de etapa primordial para fazer do Programa Nacional de Alimentação Escolar (PNAE) um espaço efetivo para a promoção da alimentação saudável e formação de sujeitos de direitos. O objetivo deste estudo foi avaliar a adequação nutricional das refeições servidas e consumidas e quantificar o desperdício de alimentos em Centros de Educação Infantil de Maceió/AL. Foram analisadas por três dias não consecutivos, pelo método de pesagem direta, as refeições de 359 crianças (17 e 63 meses). O desperdício de alimentos foi determinado pelo índice de resto-ingestão e o valor nutricional das refeições servidas e consumidas foram comparadas com os valores de referência do PNAE para energia, carboidrato, proteína, lipídio, vitaminas A e C, ferro, cálcio, zinco, magnésio e fibra. Dos 85 alimentos/preparações presentes no cardápio, 58 (68%) apresentaram percentual de resto-ingestão, superior a 10%. As refeições servidas e consumidas atenderam aproximadamente 50% do recomendado para energia e macronutrientes. A diferença entre as médias dos nutrientes ofertados e consumidos foi estatisticamente significante (p < 0,05) para fibra, vitamina A, vitamina C, cálcio, ferro e zinco.

Abstract Analyzing quantitative and qualitative aspects of school meals represents the initial stage to ensure that the National School Food Program (PNAE) is an effective space for the promotion of healthy eating habits and establishing individual rights. The objective of this study was to evaluate the nutritional adequacy of meals served and consumed, as well as quantifying food waste in Child Daycare Centers in Maceió, in the state of Alagoas. All meals served and consumed by 359 children (aged 17 to 63 months) were analyzed by the direct weighing method for three non-consecutive days in all institutions. Food waste was determined by the leftover factor and the nutritional value of meals served and consumed was compared to the PNAE reference values regarding energy, carbohydrates, protein, lipids, vitamins A and C, iron, calcium, zinc, magnesium and fiber. Of the 85 meals/preparations featured on the menu, 58 (68%) revealed a high leftover percentage; in excess of 10%. The meals served and consumed met approximately 50% of the recommended energy and macronutrient values. The difference between the averages of the nutrients offered and consumed was statistically significant (p < 0.05) for fiber, vitamin A, vitamin C, calcium, iron and zinc.

Factors associated with regular consumption of obesogenic foods: National School-Based Student Health Hurvey, 2012 / Fatores associados ao consumo regular de alimentos obesogênicos: Pesquisa Nacional de Saúde do Escolar, 2012

ABSTRACT Objective: To investigate the frequency of consumption of obesogenic foods among adolescents and its association with sociodemographic, family, behavioral, and environmental variables. Methods: Secondary data from the National School-Based Student Health Hurvey were analyzed from a representative sample of 9th grade Brazilian students (high school). A self-administered questionnaire, organized into thematic blocks, was used. The dependent variables were the consumption of deep fried snacks, packaged snacks, sugar candies, and soft drinks; consumption frequency for the seven days preceding the study was analyzed. Bivariate analysis was carried out to determine the empirical relationship between the regular consumption of these foods (≥3 days/week) with sociodemographic, family, behavioral, and school structural variables. p-value <0.20 was used as the criterion for initial inclusion in the multivariate logistic analysis, which was conducted using the "Enter" method, and the results were expressed as adjusted odds ratios with 95% confidence interval and p<0.05 indicating a statistically significance. Results: Regular food consumption ranged from 27.17% to 65.96%. The variables female gender, mobile phone ownership, Internet access at home, tobacco use, alcohol consumption, regular physical activity, eating while watching television or studying, watching television for at least 2 hours a day, and not willing to lose weight were associated in the final logistic models of all foods analyzed. Conclusion: It was concluded that fried snacks, packaged snacks, sugar candies, and soft drinks are regularly consumed by adolescents and that such consumption was associated with the sociodemographic, family, behavioral, and school structural variables.

RESUMO Objetivo: Analisar a frequência de consumo de alimentos obesogênicos entre adolescentes e sua associação com variáveis sociodemográficas, familiares, comportamentais e ambientais. Métodos: Estudou-se dados secundários da Pesquisa Nacional de Saúde do Escolar, sendo a amostra representativa de alunos do 9º ano do ensino fundamental de escolas brasileiras. Utilizou-se questionário autoaplicável organizado em blocos temáticos. Foram consideradas variáveis dependentes o consumo de salgados fritos, salgadinhos de pacote, guloseimas e refrigerantes, cuja frequência se referiu aos sete dias anteriores à pesquisa. Para associação do consumo regular dos alimentos (≥3 dias/semana) às variáveis sociodemográficas, familiares, comportamentais e estruturais da escola, foi utilizada análise bivariada, adotando-se o critério de valor de p<0,20 para inclusão inicial na análise de regressão logística multivariada, a qual foi realizada pelo método "enter". Os resultados foram expressos por Odds Ratio ajustados com respectivos intervalos de confiança de 95%, considerando associação estatisticamente significativa o valor de p<0,05. Resultados: O consumo regular dos alimentos variou de 27,17% a 65,96%. Sexo feminino, posse de telefone celular, acesso à Internet no domicílio, tabagismo, consumo de álcool, prática regular de atividade física, hábito de comer assistindo televisão ou estudando, assistir televisão no mínimo duas horas/dia e ausência de atitude visando perda de peso foram as variáveis que se associaram nos modelos logísticos finais de todos os alimentos. Conclusão: Conclui-se que o consumo de salgados fritos, salgadinhos de pacote, guloseimas e refrigerantes é regular na dieta dos adolescentes, estando seu consumo associado a variáveis sociodemográficas, familiares, comportamentais e de estrutura escolar.

Síndrome tilose hereditária e câncer de esôfago / Hereditary tylosis syndrome and esophagus cancer

A tilose palmo-plantar é um distúrbio autossômico dominante caracterizado por uma hiperceratose palmo-plantar. Em geral, desenvolve-se na segunda infância e se acentua em áreas de pressão. Existem duas formas familiares de tilose palmo-plantar: a não epidermolítica e a epidermolítica. Os pacientes com tilose palmo-plantar forma epidermolítica apresentam uma chance até 40 por cento maior de desenvolver carcinoma de células escamosas do esôfago. A associação de tilose palmo-plantar com neoplasia esofágica é denominada síndrome de Howel-Evans.

Tylosis palmoplantaris is an autosomal dominant disorder characterized by hyperkeratosis of palms and soles. Lesions start during childhood and are more evident in areas of pressure. Familial tylosis palmoplantaris comprises two forms: epidermolytic and non-epidermolytic. Patients with the epidermolytic variant have up to 40 percent higher chance of developing squamous cell carcinoma of the esophagus. The association of tylosis palmoplantaris with esophageal cancer is called Howel-Evans syndrome.

[Hereditary tylosis syndrome and esophagus cancer]. / Síndrome tilose hereditária e câncer de esôfago.

Tylosis palmoplantaris is an autosomal dominant disorder characterized by hyperkeratosis of palms and soles. Lesions start during childhood and are more evident in areas of pressure. Familial tylosis palmoplantaris comprises two forms: epidermolytic and non-epidermolytic. Patients with the epidermolytic variant have up to 40% higher chance of developing squamous cell carcinoma of the esophagus. The association of tylosis palmoplantaris with esophageal cancer is called Howel-Evans syndrome.