Disease progression in Sanfilippo type B: Case series of Brazilian patients.

Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.

Behavioral Assessment of Central Auditory Processing in Turner Syndrome.

Introduction Turner syndrome (TS) affects ∼ 1 in 2,500 live births. The presence of hearing alterations is one of the comorbidities found in this syndrome. Objective The present study aimed to evaluate the central auditory abilities in TS and to associate the alterations found with the cytogenetic pattern of the syndrome. Methods We included children and adults aged 9 to 39 years old, diagnosed with TS, with numerical or structural alterations of sex chromosomes in their karyotype. A battery of behavioral tests of central auditory processing (CAP) was performed, including a test within the modalities: monoaural low-redundancy, dichotic listening, binaural interaction, and temporal processing (resolution and ordering). We studied auditory skills in the total sample and in the sample stratified by age, divided into groups: G1 (9 to 13 years old), G2 (14 to 19 years old), and G3 (20 to 31 years old). For the association of the cytogenetic pattern, the division was T1 (chromosome monosomy X), and T2 (other TS cytogenetic patterns). Statistical analysis presented data expressed as median and interquartile range for numerical data and as frequency and percentage for categorical data. Results We found alterations in four auditory skills in the three age groups, but there was a statistically significant difference between the age groups only in the Gaps in Noise Test (GIN) ( p -value = 0.009). Regarding karyotype, a greater number of alterations in the T1 cytogenetic pattern (chromosome monosomy X) was observed in four auditory skills, but without a statistically significant difference. Conclusion The alterations found point to an impairment in CAP in TS.

Efeito da pandemia por Covid-19 nos cuidados de indivíduos com distrofia muscular de Duchenne / Covid-19 pandemic's effect on the care of individuals with Duchenne muscular dystrophy

INTRODUCTION: Since December 2019, the scientific community has been mobilized to contain the COVID-19 pandemic. Although individuals with Duchenne Muscular Dystrophy (DMD) have restrictive lung disease, risk of immunosuppression and associated cardiomyopathy, they are not considered to be a risk group for COVID-19. DMD is a neuromuscular, genetic and progressive disease, with early childhood development. In order to manage the disease, multidisciplinary follow-up is necessary to improve this patient's quality of life. OBJECTIVE: Identify the impact of the pandemic on the care of patients with DMD and its repercussions. METHOD: This is a cross-sectional, quantitative and descriptive study. The sample consisted of patients diagnosed with DMD aged between 4 and 18 years, followed up at the neuropediatrics service. Data collection was carried out by an interview with those responsible for the patient and evaluation of the medical records, using a questionnaire. Statistical analysis was descriptive using central tendency and dispersion measures. RESULTS: Among the 44 patients included, the median age was 12 years and the predominant type of gene mutation was deletion (56.8%). The median age of first symptoms was 4 years. Thirteen patients had contact with family members positive for COVID-19 and tested positive for the disease. Eleven received the vaccine against COVID-19. Medical followups suffered a great reduction in the pandemic period, as well as respiratory and motor physiotherapy. CONCLUSION: The pandemic interfered with multidisciplinary care for patients with DMD. As a chronic and degenerative disease, individuals with DMD require ongoing care, which was interrupted by the pandemic scenario.

INTRODUÇÃO: Desde dezembro de 2019, a comunidade científica está mobilizada para a contenção da pandemia pela COVID-19. Embora indivíduos portadores de Distrofia Muscular de Duchenne (DMD) apresentem doença pulmonar restritiva, risco de imunossupressão e cardiomiopatia associada, não são grupo de risco para a COVID-19. DMD é doença neuromuscular, genética e progressiva, de início na infância. Para manejo da doença, faz-se necessário acompanhamento multidisciplinar para melhora da qualidade de vida. OBJETIVO: Identificar o impacto da pandemia nos cuidados aos pacientes com DMD e suas repercussões. MÉTODOS: Trata-se de um estudo transversal, quantitativo e descritivo. A amostra foi composta por pacientes com diagnóstico de DMD com idade entre 4 e 18 anos acompanhados no serviço de neuropediatria. A coleta de dados foi realizada por entrevista com responsáveis e avaliação do prontuário, a partir de um questionário. A análise estatística foi descritiva com uso de medida de tendência central e dispersão. RESULTADOS: Dentre os 44 pacientes incluídos, a mediana de idade foi de 12 anos e o tipo de mutação gênica predominante a deleção (56,8%). A mediana de idade dos primeiros sintomas foi de 4 anos. Treze pacientes tiveram contato com familiares positivos para COVID-19 e testaram positivo para a doença. Onze receberam a vacina contra COVID-19. Os acompanhamentos médicos sofreram grande redução no período pandêmico, bem como a fisioterapia respiratória e motora. CONCLUSÃO: A pandemia interferiu nos atendimentos multidisciplinares aos pacientes com DMD. Como uma doença crônica e degenerativa, os indivíduos com DMD necessitam de cuidados contínuos, o que foi interrompido pelo cenário pandêmico.

Agreement Between Alberta Infant Motor Scale Assessment and Maternal Perception of Motor Development in Full-Term Infants.

OBJECTIVES: To verify the agreement between the Alberta Infant Motor Scale assessment and maternal perception of the motor development in full-term infants. METHODS: This is a cross-sectional study involving 161 infants and mothers. Children were assessed with the Alberta Infant Motor Scale (AIMS) for motor developmental classification. Mothers completed questionnaires aiming to identify maternal profiles and impressions about their children's development. The kappa test was used to analyze the concordance between AIMS and mother perceptions. RESULTS: A total of 83.2% of the sample was classified as typically developing and 16.8% as suspected or delayed development. The maternal impression indicates that 77% of infants are developing typically, 19.9% perceived their infants' development as advanced, and 3.1% delayed development. There was low agreement between the mothers' perceptions and AIMS classifications (kappa = 0.153). CONCLUSIONS: Maternal perception of their infant's development was unsatisfactory for evaluation of motor development because their perceptions did not agree with the findings of the AIMS.

Sanfilippo syndrome type B: Analysis of patients diagnosed by the MPS Brazil Network.

Mucopolysaccharidosis type IIIB is a rare autosomal recessive disorder characterized by deficiency of the enzyme N-acetyl-alpha-d-glucosaminidase (NAGLU), caused by biallelic pathogenic variants in the NAGLU gene, which leads to storage of heparan sulfate and a series of clinical consequences which hallmark is neurodegeneration. In this study clinical, epidemiological, and biochemical data were obtained from MPS IIIB patients diagnosed from 2004-2019 by the MPS Brazil Network ("Rede MPS Brasil"), which was created with the goal to provide an easily accessible and comprehensive investigation of all MPS types. One hundred and ten MPS IIIB patients were diagnosed during this period. Mean age at diagnosis was 10.9 years. Patients were from all over Brazil, with a few from abroad, with a possible cluster of MPS IIIB identified in Ecuador. All patients had increased urinary levels of glycosaminoglycans and low NAGLU activity in blood. Main clinical symptoms reported at diagnosis were coarse facies and neurocognitive regression. The most common variant was p.Leu496Pro (30% of alleles). MPS IIIB seems to be relatively frequent in Brazil, but patients are diagnosed later than in other countries, and reasons for that probably include the limited awareness about the disease by health professionals and the difficulties to access diagnostic tests, factors that the MPS Brazil Network is trying to mitigate.

Efeito inibitório da via auditiva eferente na síndrome de Turner / Efferent Auditory Pathways Inhibition in Turner syndrome

RESUMO Objetivo investigar o efeito inibitório da via auditiva eferente na síndrome de Turner e relacionar com o perfil citogenético. Método estudo descritivo transversal com grupo de comparação. Amostra: Grupo estudo formado por 40 pacientes com síndrome de Turner (17,6 anos); e Grupo controle constituído por 54 indivíduos (18,9 anos), do sexo feminino sem síndrome. Os indivíduos selecionados foram submetidos à pesquisa do efeito inibitório da via auditiva eferente. Resultados A média do Efeito inibitório da via auditiva eferente no grupo estudo na orelha direita foi 0,4 dB e no grupo comparação foi de 1,9 dB, entretanto na orelha esquerda a média do efeito inibitório da via auditiva eferente foi 1,4 dB no grupo estudo e 0,8 dB no grupo comparação. O efeito inibitório da via auditiva eferente foi presente em 14 indivíduos com monossomia e em 15 com outras alterações citogenéticas. Conclusão No grupo estudo o valor do efeito inibitório da via auditiva eferente foi significantemente maior na orelha esquerda e significativamente menor que o grupo controle na direita. Não houve diferença significativa no efeito inibitório da via auditiva eferente entre os tipos de cariótipo.

ABSTRACT Purpose The goal of this study is to investigate the efferent auditory pathways inhibition in Turner's syndrome and to relate it to the cytogenetic profile. Methods This is a cross-sectional study with a comparison group. A sample with 94 participants divided into two groups: The study group was a sample of 40 patients diagnosed with Turner's syndrome (17.6 years of age). The control group was composed of 54 volunteers (18.9 years of age), female, without syndrome. The selected individuals were submitted to efferent auditory pathways inhibition research. Results The mean of the inhibitory effect of the efferent auditory pathway in the study group in the right ear was 0.4 dB and in the comparison group it was 1.9 dB, however in the left ear the mean of the inhibitory effect of the efferent auditory pathway was 1.4 dB in the study group and 0.8 dB in the comparison group. The inhibitory effect of the efferent auditory pathway was present in 14 individuals with monosomy and in 15 with other cytogenetic alterations. Conclusions In the study group, the efferent auditory pathways inhibition value was significantly higher in the left ear and significantly lower than the control group in the right ear. There was no significant difference in efferent auditory pathways inhibition of right ear and left ear between the karyotype types.

Efferent Auditory Pathways Inhibition in Turner syndrome. / Efeito inibitório da via auditiva eferente na síndrome de Turner.

PURPOSE: The goal of this study is to investigate the efferent auditory pathways inhibition in Turner's syndrome and to relate it to the cytogenetic profile. METHODS: This is a cross-sectional study with a comparison group. A sample with 94 participants divided into two groups: The study group was a sample of 40 patients diagnosed with Turner's syndrome (17.6 years of age). The control group was composed of 54 volunteers (18.9 years of age), female, without syndrome. The selected individuals were submitted to efferent auditory pathways inhibition research. RESULTS: The mean of the inhibitory effect of the efferent auditory pathway in the study group in the right ear was 0.4 dB and in the comparison group it was 1.9 dB, however in the left ear the mean of the inhibitory effect of the efferent auditory pathway was 1.4 dB in the study group and 0.8 dB in the comparison group. The inhibitory effect of the efferent auditory pathway was present in 14 individuals with monosomy and in 15 with other cytogenetic alterations. CONCLUSIONS: In the study group, the efferent auditory pathways inhibition value was significantly higher in the left ear and significantly lower than the control group in the right ear. There was no significant difference in efferent auditory pathways inhibition of right ear and left ear between the karyotype types.

OBJETIVO: investigar o efeito inibitório da via auditiva eferente na síndrome de Turner e relacionar com o perfil citogenético. MÉTODO: estudo descritivo transversal com grupo de comparação. Amostra: Grupo estudo formado por 40 pacientes com síndrome de Turner (17,6 anos); e Grupo controle constituído por 54 indivíduos (18,9 anos), do sexo feminino sem síndrome. Os indivíduos selecionados foram submetidos à pesquisa do efeito inibitório da via auditiva eferente. RESULTADOS: A média do Efeito inibitório da via auditiva eferente no grupo estudo na orelha direita foi 0,4 dB e no grupo comparação foi de 1,9 dB, entretanto na orelha esquerda a média do efeito inibitório da via auditiva eferente foi 1,4 dB no grupo estudo e 0,8 dB no grupo comparação. O efeito inibitório da via auditiva eferente foi presente em 14 indivíduos com monossomia e em 15 com outras alterações citogenéticas. CONCLUSÃO: No grupo estudo o valor do efeito inibitório da via auditiva eferente foi significantemente maior na orelha esquerda e significativamente menor que o grupo controle na direita. Não houve diferença significativa no efeito inibitório da via auditiva eferente entre os tipos de cariótipo.

Association between cytogenetic alteration and the audiometric profile of individuals with Turner syndrome / Relação entre alteração citogenética e o perfil audiométrico de indivíduos com síndrome de Turner

Abstract Introduction: Turner syndrome is a frequent genetic disorder that affects female individuals and covers a large phenotypic variability. Scientific literature suggests an association between hearing loss and Turner syndrome, but it remains a controversial topic. Objective: To associate the cytogenetic alteration with the audiometric profile of individuals with Turner syndrome. Methods: Cross-sectional study, with a hospital-based, convenience sample. Patients diagnosed with Turner syndrome were included and those with difficulty understanding the audiometry and/or other associated syndromes were excluded. The participants were studied with pure tone audiometry. Results: Of the 65 patients included, 36.9% had X chromosome monosomy and 63.0% had other alterations. Regarding the audiometry, 64.6% had normal thresholds and 35.3% had hearing impairment. Of these, 30.4% had hybrid hearing loss, 26.0% alteration at 6 and/or 8 kHz, 17.3% had conductive hearing loss, 13.0% sensorineural loss and 13.0% had mixed hearing loss. We observed that the mild degree was the most frequent one. There was no statistically significant association between the cytogenetic type of Turner syndrome and the presence or absence of hearing loss, or with the type and degree of hearing loss. Conclusion: The cytogenetic alteration in Turner syndrome was not associated with the audiometric profile, which showed variability regarding the type and degree of hearing loss.

Resumo Introdução: A síndrome de Turner é uma alteração frequente e genética que acomete indivíduos do sexo feminino e abrange grande variabilidade fenotípica. A literatura científica sugere uma relação entre perda auditiva e síndrome de Turner, porém ainda é um tema controverso. Objetivo: Relacionar a alteração citogenética com o perfil audiométrico de indivíduos com síndrome de Turner. Método: Estudo transversal, com amostra de conveniência, de base hospitalar. Foram incluídas pacientes com diagnóstico de síndrome de Turner e excluídas as com dificuldade para compreender a audiometria e/ou outras síndromes associadas. As participantes foram submetidas à audiometria tonal. Resultados: Das 65 pacientes incluídas, 36,9% apresentaram monossomia do cromossomo X e 63,0%, outras alterações. Com relação à audiometria, 64,6% apresentaram limiares dentro da normalidade e 35,3% alteração auditiva. Dessas, 30,4% apresentaram perda auditiva híbrida, 26,0% alteração em 6 e/ou 8 KHz; 17,3% perda auditiva condutiva, 13,0% perda neurossensorial e 13,0% perda auditiva mista. Observamos que o grau leve foi o mais frequente. Não foi observada associação estatiscamente significativa entre o tipo citogenético da síndrome de Turner e a presença ou não perda auditiva, ou com o tipo e grau de perda auditiva. Conclusão: A alteração citogenética na síndrome de Turner não teve associação com o perfil audiométrico, o qual apresentou variabilidade quanto ao tipo e grau da perda auditiva.

Risk factors for survival after head and neck cancer: a cohort study in the south of Espirito Santo state

Introduction: Head and check squamous cell carcinomas (HNSCC) affects the Brazilian population with a high incidence and usually has a poor prognosis. Objective: To evaluate the risk factors for survival of patients diagnosed with HNSCC and investigate the influence of epidemiological and clinical factors on the prognostic of HNSCC in southeastern Brazil. Materials and Methods: Clinical records of 211 patients with head and neck squamous cell carcinomas diagnosed and treated between 2010 and 2018 at a reference hospital for oncology, were selected. Clinical and pathological characteristics at diagnosis and for 5 years follow up were collected. The Kaplan-Meier Curve with the Log-Rank test assessed survival, and forward stepwise multivariate logistic regression model was performed to determine the factors affecting HNSCC survival. Results: The 5-year overall survival was 30.0%. Laryngeal cancer was the most prevalent (34.1%), followed by oropharynx (33.6%) and oral cavity (24.2%). About 64% of patients had locally advanced tumors (T3 and T4) and 75.4% of the patients were diagnosed as being in the advanced clinical stages (III and IV). In the multivariate analysis, the locally advanced tumors (OR=2.748; 95%CI:1.310- 5.765), palliative chemotherapy (OR=15.757; 95%CI:5.868-42.309) and metastasis during oncological follow-up (OR=11.602; 95%CI:1.380-97.507) were associated with a poor prognosis. Conclusion: The survival rate was considered low when compared with the literature. Locally advanced tumors, palliative chemotherapy, and the appearance of metastases during follow-up were considered the most important risk factors associated with a low HNSCC survival.

Introdução: O carcinoma de células escamosas (CCE) de cabeça e pescoço possui alta incidência na população brasileira e normalmente está associado a um prognóstico desfavorável. Objetivo: Avaliar os fatores de risco para sobrevida de pacientes diagnosticados com CCE de cabeça e pescoço e investigar a influência de fatores clínicoepidemiológicos no prognóstico do CCE. Materiais e Métodos: Foram selecionados prontuários de 211 pacientes com CCE de cabeça e pescoço diagnosticados e tratados entre 2010 e 2018 em um hospital de referência em oncologia. Foram coletadas as características clínico-patológicas no momento do diagnóstico e nos 5 anos de acompanhamento. A curva de Kaplan-Meier com o teste Log-Rank avaliou a sobrevivência e o modelo de regressão logística multivariada progressiva foram realizados para determinar os fatores que afetaram a sobrevivência do CCE. Resultados: A sobrevida global em 5 anos foi de 30,0%. O câncer de laringe foi o mais prevalente (34,1%), seguido de orofaringe (33,6%) e cavidade oral (24,2%). 64% dos pacientes apresentavam tumores localmente avançados (T3 e T4) e 75,4% dos pacientes foram diagnosticados em estádios clínicos avançados (III e IV). Na análise multivariada, os tumores localmente avançados (RC = 2,748; IC 95%: 1,310-5,765), quimioterapia paliativa (RC = 15,757; IC 95%: 5,868-42,309) e metástases durante o acompanhamento oncológico (RC = 11,602; IC 95%: 1,380-97,507) foram associados a um pior prognóstico. Conclusão: A taxa de sobrevida foi considerada baixa. Tumores localmente avançados, quimioterapia paliativa e aparecimento de metástases durante o seguimento foram considerados os fatores de risco mais importantes associados a uma baixa sobrevida.

Clinical assessment of the use of topical liquid diclofenac following laser microporation of cutaneous neurofibromas in individuals with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with a prevalence of 1:3000 births and a wide variety of clinical manifestations. Cutaneous neurofibromas (cNF) are among the most common visible manifestations of NF1 and present a major clinical burden for patients. NF1 patients with cNF often report decreased quality of life, emotional well-being and physical comfort. Developing effective medical therapies for cNF has been identified as a priority for the majority of adults with NF1. METHODS: The study was an open, controlled and prospective proof-of-concept clinical trial. The topical treatment consisted of two steps: cNF microporation using a laser device followed by topical application of one drop of diclofenac 25 mg/mL on the surface of the cNF (T neurofibroma = treatment) or physiological saline (C neurofibroma = control) and reapplied twice daily for 3 days. Neurofibroma assessments included visual and dermatoscopy observations noting color and presence of necrosis, presence of flaccidity, measurements in two dimensions, photographs, and histopathology after excision. The primary efficacy variable was the presence of tissue necrosis. The primary safety variable was the occurrence of treatment-related adverse events. RESULTS: Six patients were included in the study. The treatment resulted in transitory topical changes (healing of the microporation grid with formation of scintillating tissue layer, hyperemia and desquamation), with no statistically significant variation in the dimensions of the T and C neurofibromas in relation to pretreatment measurements. There was no necrosis in the T or C neurofibromas. In the histopathological analysis, there was no significant difference in the distribution of chronic (lymphocytic) inflammatory infiltrate in the papillary reticular dermis (subepithelial), type of infiltrate (diffuse, perivascular, or both), presence of fibrosis, and presence of atrophy among the T and C neurofibromas. No adverse events attributable to the use of diclofenac were reported during the treatment period. CONCLUSIONS: Treatment did not result in significant alterations in terms of presence of tissue necrosis, size, or histopathological features in the T neurofibromas or in comparison to the C neurofibromas. Topical diclofenac with laser microporation was well-tolerated, with no adverse events attributable to diclofenac reported. Whether these observations are due to minimal systemic and neurofibroma exposure remain to be explored in dosage studies with larger patient groups. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03090971) retrospectively registered March 27, 2017.

Clinical oral profile of pediatric patients with atopic dermatitis: A cross-sectional study.

OBJECTIVES: This work aims to describe oral health conditions, eating habits, and oral hygiene in pediatric and adolescent patients with atopic dermatitis and correlate them with the severity of the Scoring Atopic Dermatitis (SCORAD). Also, we aim to estimate the effect of several variables on the diagnosis of dental caries in these patients. MATERIAL AND METHODS: A total of 92 children and adolescents with atopic dermatitis had their oral cavities examined. The effect of independent variables on the diagnosis of dental caries (outcome) was assessed using multiple binary logistic regression model. RESULTS: Mild patients presented higher score of decayed, missing, and filled teeth in permanent dentition than moderate patients (p = 0.040). In the multivariable regression final model, the covariates using inhaled corticoid (OR = 6.4; p = 0.003), type of teething [deciduous dentition (OR = 7.9; p = 0.027) and mixed dentition (OR = 10.5; p = 0.007)], and brushing quality [poor mechanical control (OR = 10.6; p < 0.0001)] demonstrated significant direct effect on the diagnosis of dental caries. CONCLUSIONS: Our findings suggest that the presence of dental biofilm, use of inhaled corticoid, and type of teething are related to the presence of caries in atopic dermatitis patients.

Association between cytogenetic alteration and the audiometric profile of individuals with Turner syndrome.

INTRODUCTION: Turner syndrome is a frequent genetic disorder that affects female individuals and covers a large phenotypic variability. Scientific literature suggests an association between hearing loss and Turner syndrome, but it remains a controversial topic. OBJECTIVE: To associate the cytogenetic alteration with the audiometric profile of individuals with Turner syndrome. METHODS: Cross-sectional study, with a hospital-based, convenience sample. Patients diagnosed with Turner syndrome were included and those with difficulty understanding the audiometry and/or other associated syndromes were excluded. The participants were studied with pure tone audiometry. RESULTS: Of the 65 patients included, 36.9% had X chromosome monosomy and 63.0% had other alterations. Regarding the audiometry, 64.6% had normal thresholds and 35.3% had hearing impairment. Of these, 30.4% had hybrid hearing loss, 26.0% alteration at 6 and/or 8kHz, 17.3% had conductive hearing loss, 13.0% sensorineural loss and 13.0% had mixed hearing loss. We observed that the mild degree was the most frequent one. There was no statistically significant association between the cytogenetic type of Turner syndrome and the presence or absence of hearing loss, or with the type and degree of hearing loss. CONCLUSION: The cytogenetic alteration in Turner syndrome was not associated with the audiometric profile, which showed variability regarding the type and degree of hearing loss.

Phonological remediation in schoolchildren with ADHD and dyslexia. / Remediação fonológica em escolares com TDAH e dislexia.

PURPOSE: To compare the performance in phonological processing skills, reading speed and reading comprehension before and after phonological remediation in a restricted group of schoolchildren with Attention Deficit Hyperactivity Disorder (ADHD) and with dyslexia. METHODS: Thirty-two schoolchildren from the 2nd to 8th year of Elementary School of both genders, with diagnosis of ADHD and Dyslexia according to the DSM-5, participated in this study. All patients underwent Phonological Remediation Program consisted of 18 weekly sessions. RESULTS: The results, expressed in z scores, showed a statistically significant difference between before and after remediation assessments in phonological processing skills, such as syllabic and phonemic awareness, working memory and lexical access. Rhyming task was analyzed separately because it represents another level of segmentation and, for this result, there was no significance. Besides these results, there was a statistically significant difference in reading speed and reading comprehension. CONCLUSION: The phonological remediation program contributes to the development of phonological processing, reading speed and reading comprehension in this population.

OBJETIVO: Comparar o desempenho da avaliação do processamento fonológico, velocidade de leitura e compreensão de texto antes e depois da aplicação de um programa de remediação fonológica em um grupo restrito de escolares com Transtorno do Déficit de Atenção e Hiperatividade (TDAH) e dislexia. MÉTODOS: Participaram deste estudo 32 escolares do 2º ao 8º ano do Ensino Fundamental, de ambos os sexos, com diagnóstico de TDAH e dislexia de acordo com o DSM-5, atendidos no Ambulatório de Neurologia Infantil do IPPMG/UFRJ. Todos os pacientes foram submetidos ao programa de remediação fonológica, que consistiu em 18 sessões semanais. RESULTADOS: Os resultados, expressos em escore z, indicaram diferença estatisticamente significativa entre as avaliações pré e pós-remediação nas habilidades do processamento fonológico, como em consciência silábica e fonêmica, memória de trabalho e acesso lexical. A tarefa de rima foi analisada separadamente, pois é considerada uma tarefa com nível de segmentação distinto de outros níveis silábicos e, para este resultado não houve significância. Além desses, houve diferença estatisticamente significativa também nos testes que medem velocidade de leitura e compreensão de texto. CONCLUSÃO: O programa de remediação fonológica contribui para o desenvolvimento do processamento fonológico, leitura e compreensão textual nesta população.

Oral mycobiome identification in atopic dermatitis, leukemia, and HIV patients - a systematic review.

INTRODUCTION: Oral mycobiome profiling is important to understand host-pathogen interactions that occur in various diseases. Invasive fungal infections are particularly relevant for patients who have received chemotherapy and for those who have HIV infection. In addition, changes in fungal microbiota are associated with the worsening of chronic conditions like atopic dermatitis (AD). This work aims, through a systematic review, to analyze the methods used in previous studies to identify oral fungi and their most frequent species in patients with the following conditions: HIV infection, leukemia, and atopic dermatitis. METHODS: A literature search was performed on several different databases. Inclusion criteria were: written in English or Portuguese; published between September 2009 and September 2019; analyzed oral fungi of HIV-infected, leukemia, or AD patients. RESULTS: 21 studies were included and the most identified species was Candida. The predominant methods of identification were morphological (13/21) and sugar fermentation and assimilation tests (11/21). Polymerase chain reaction (PCR) was the most used molecular method (8/21) followed by sequencing techniques (3/21). CONCLUSIONS: Although morphological and biochemical tests are still used, they are associated with high-throughput sequencing techniques, due to their accuracy and time saving for profiling the predominant species in oral mycobiome.

Can simple and low-cost motor function assessments help in the diagnostic suspicion of Duchenne muscular dystrophy? / Avaliações simples da função motora e de baixo custo podem ajudar na suspeita diagnóstica da distrofia muscular de Duchenne?

Abstract Objective: Duchenne muscular dystrophy, an X-linked genetic disease, leads to progressive muscle weakness mainly in the lower limbs. Motor function tests help to monitor disease progression. Can low-cost, simple assessments help in the diagnostic suspicion of Duchenne muscular dystrophy? The authors aim to define the sensitivity of time to rise from the floor, time to walk 10 meters, and time to run 10 meters, evaluating them as eventual diagnostic screening tools. Methods: This is an analytical, observational, retrospective (1998-2015), and prospective study (2015-2018). Cases were recruited from the database of the pediatric neurology department and the healthy, from child care consultations, with normal gait development (up to 15 months) and without other comorbidities (neuromuscular, pulmonary, heart diseases) from the same university hospital. Results: 128 Duchenne muscular dystrophy patients and 344 healthy children were analyzed, equally distributed in age groups. In Duchenne muscular dystrophy, there is a progressive increase in the means of the times to perform the motor tests according to the age group, which accelerates very abruptly after 7 years of age. Healthy children acquire maximum motor capacity at 6 years and stabilize their times. The time to rise showed a p-value <0.05 and a strong association (effect size [ES] >0.8) in all age groups (except at 12 years), with time to walk 10 meters from 9 years, and with time to run 10 meters , from 5 years. The 100% sensitivity points were defined as follows: time to rise, at 2 s; time to walk 10 meters, 5 s; time to run 10 meters, 4 s. Conclusions: Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy, a previously incurable disease with new perspectives for treatment.

Resumo Objetivo: A distrofia muscular de Duchenne, doença genética ligada ao X, determina fraqueza muscular progressiva principalmente em membros inferiores. Os testes de função motora ajudam a monitorar a progressão da doença. Avaliações simples de baixo custo podem ajudar na suspeita diagnóstica da distrofia muscular de Duchenne? Objetivamos definir a sensibilidade do tempo levantar, tempo andar 10 metros e tempo correr 10 metros, avaliando-os como eventuais ferramentas de triagem diagnóstica. Métodos: Estudo analítico, observacional, retrospectivo (1998 até 2015) e prospectivo (2015 até 2018). Os casos foram recrutados do banco de dados do serviço de neurologia infantil e os saudáveis, de consultas de puericultura, com desenvolvimento de marcha normal (até os 15 meses) e sem outras comorbidades (neuromusculares, pneumopatias, cardiopatias), do mesmo hospital universitário. Resultados: Foram analisados 128 pacientes com distrofia muscular de Duchenne e 344 saudáveis, distribuídos igualmente em faixas etárias. Na distrofia muscular de Duchenne ocorre aumento progressivo das médias dos tempos para realizar as provas motoras, de forma acentuada a partir dos 7 anos. Os saudáveis estabilizam os tempos a partir dos 6 anos, adquirindo capacidade motora máxima. O tempo de levantar apresentou p-valor <0,05 e forte associação (TE >0,8) em todas as faixas etárias (exceto aos 12 anos), tempo de andar 10 metros a partir de 9 anos e o tempo de correr 10 metros, dos 5 anos. Os pontos de 100% sensibilidade foram definidos: tempo de levantar aos 2 segundos; tempo de andar, 5 segundos e tempo de correr 10 metros, 4 segundos. Conclusões: O tempo de levantar é útil e simples na triagem de doenças neuromusculares como a distrofia muscular de Duchenne, doença antes incurável com novas perspectivas de tratamento.

High-throughput nucleotide sequencing for bacteriome studies in oral squamous cell carcinoma: a systematic review.

PURPOSE: Dysbiosis has been identified in oral squamous cell carcinoma (OSCC). The aim of this study was to carry out a systematic review of an electronic research that was carried out on articles published between January 2008 and September 2018. METHODS: Eight studies were selected after applying the inclusion and exclusion criteria. RESULTS: All articles targeted the hypervariable regions of the 16S rRNA gene. At the phylum level, it was found reduction of Bacteroidetes (2/8 studies) and increase of Firmicutes (2/8 studies). At the genus level, Rothia increased (1/8 studies) and decreased (2/8 studies) in tumor samples, and Streptococcus also was found increased (3/8 studies) and reduced (3/8 studies). Fusobacterium only increased in OSCC samples (3/8 studies). At species level, an increase in F. nucleatum subsp. polymorphum was more associated to OSCC (2/8 studies) than with controls, as was P. aeruginosa (3/8 studies). CONCLUSION: In summary, the results corroborated dysbiosis in OSCC patients, with enrichment of microbial taxa that are associated with inflammation and production of acetaldehyde. However, variations of study design and sample size were observed among the studies, as well as a shortage of more detailed analyses of possible correlations between risk habits and OSCC. This lack of more detailed analysis may be the cause of the inconsistencies in regard of the alterations reported for certain genera and species. In conclusion, there is an association between OSCC and oral microbiota dysbiosis, but its role in oral carcinogenesis needs to be clarified in more detail.

Understanding the Landscape of X-linked Variants Causing Intellectual Disability in Females Through Extreme X Chromosome Inactivation Skewing.

Intellectual disability (ID) affects 30% more males than females. This sex bias can be attributed to the enrichment of genes on the X chromosome playing essential roles in the central nervous system and their hemizygous state on males. Moreover, as a result of X chromosome inactivation (XCI), most genes on one of the X chromosomes in female somatic cells are epigenetically silenced, so that females carrying X-linked variants are not expected to be so severely affected as males. Consequently, the knowledge about X-linked ID (XLID) in females is still scarce. Herein, we used extreme XCI skewing (≥ 90%) to predict X-linked variants in females with idiopathic ID. XCI profiles from 53 probands were estimated from blood and buccal mucosa through a methylation-sensitive AR/RP2 assay. DNA samples with extreme XCI skewing were then submitted to array-comparative genomic hybridization and whole-exome sequencing. Seven females (13.2%) exhibited extreme XCI skewing, a percentage significantly higher than expected for healthy females in our population. XLID-potentially related variants were identified in five patients with extreme XCI skewing, including one pathogenic rstructural rearrangement [der(X) chromosome from a t(X;2)] and four single nucleotide variants in NLGN4X, HDAC8, TAF1, and USP9X genes, two of which affecting XCI escape genes. XCI skewing showed to be an outstanding approach for the characterization of molecular mechanisms underlying XLID in females. Beyond expanding the spectrum of variants/phenotypes associated with ID, our results pointed to compensatory biological pathways underlying XCI and uncover new insights into the involvement of escape genes on XLID, impacting genetic counseling.

Dihydrofolate Reductase (DHFR) del19bp Polymorphism and Down Syndrome Offspring.

Down syndrome (DS) is the most common form of mental disability of genetic etiology. Nondisjunction of chromosome 21 is the leading cause of the syndrome. In general, free trisomy 21 cases originate from missegregation in maternal meiosis. Several reports have suggested an association between genetic variants in genes encoding folate metabolizing enzymes and the predisposition to chromosome missegregation. We have conducted a case-control study of 109 DS case mothers (MDS) and 248 control mothers (CM) to assess the association between DHFR del19bp polymorphism and an increased risk of bearing a DS child. Genomic DNA was extracted from buccal cells, and molecular analysis of DHFR del19pb polymorphism was performed by polymerase chain reaction (PCR). Both MDS and CM allelic and genotypic distributions were in Hardy-Weinberg equilibrium. The frequency of DHFR del19pb-mutated allele was 0.54 in MDS and 0.46 in CM. Overall analysis showed that the mutant allele was borderline associated with DS risk (OR 1.38; 95% CI 1.00-1.89; P = 0.05) and a weak positive association for del/del and/or wt/del genotypes of DHFR del19pb polymorphism compared to homozygous wt/wt genotype was identified (OR = 1.75; 95% CI 1.01-3.03; P = 0.05). When we have analyzed data stratified by age, there is an increased risk of bearing a DS child associated with the polymorphic allele (OR = 1.49; 95% CI 1.03-2.16; P = 0.03), suggesting that DHFR del 19-bp polymorphism could be an independent risk factor for DS in women aged < 40 years old.

Incidence and risk factors of communication, swallowing, and orofacial myofunctional disorders in children and adolescents with cancer and benign neoplasms.

PURPOSE: To describe the incidence and risk factors of communication, swallowing, and orofacial myofunctional disorders in a cohort of children and adolescents with cancer and benign neoplasms. METHODS: A prospective cohort study conducted with children aged ⩾ 2 years and adolescents of both genders admitted at the Pediatric Oncology Department of the Instituto Nacional de Câncer (INCA) between March 2014 and April 2015. Study participants were submitted to a Speech-Language Pathology (SLP) assessment at three different times: (T1) at hospital admission; (T2) six months after admission; (T3) one year after admission. RESULTS: One hundred and sixty individuals were evaluated. At the time of hospital admission, 68 individuals (42.5%) presented with some type of SLP disorder. After one year of follow-up, 22.8% of the patients had developed new impairments. The occurrence of new speech-language disorders had a statistically significant association with the tumor site. In the risk analysis for the development of speech-language disorders with respect to the primary tumor site, compared to other sites, the central nervous system (CNS) tumor group was 8.29 times more likely to present some new alterations, while the head and neck (HN) tumor group had a 10.36-fold higher risk. CONCLUSION: An incidence of 22.8% for communication, swallowing, and orofacial myofunctional disorders was observed. The development of these disorders was greater in individuals with tumors in the CNS and in the HN region.

Can simple and low-cost motor function assessments help in the diagnostic suspicion of Duchenne muscular dystrophy?

OBJECTIVE: Duchenne muscular dystrophy, an X-linked genetic disease, leads to progressive muscle weakness mainly in the lower limbs. Motor function tests help to monitor disease progression. Can low-cost, simple assessments help in the diagnostic suspicion of Duchenne muscular dystrophy? The authors aim to define the sensitivity of time to rise from the floor, time to walk 10meters, and time to run 10meters, evaluating them as eventual diagnostic screening tools. METHODS: This is an analytical, observational, retrospective (1998-2015), and prospective study (2015-2018). Cases were recruited from the database of the pediatric neurology department and the healthy, from child care consultations, with normal gait development (up to 15 months) and without other comorbidities (neuromuscular, pulmonary, heart diseases) from the same university hospital. RESULTS: 128 Duchenne muscular dystrophy patients and 344 healthy children were analyzed, equally distributed in age groups. In Duchenne muscular dystrophy, there is a progressive increase in the means of the times to perform the motor tests according to the age group, which accelerates very abruptly after 7 years of age. Healthy children acquire maximum motor capacity at 6 years and stabilize their times. The time to rise showed a p-value <0.05 and a strong association (effect size [ES] >0.8) in all age groups (except at 12 years), with time to walk 10 meters from 9 years, and with time to run 10 meters , from 5 years. The 100% sensitivity points were defined as follows: time to rise, at 2s; time to walk 10 meters, 5s; time to run 10 meters, 4s. CONCLUSIONS: Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy, a previously incurable disease with new perspectives for treatment.