Association of laboratory markers and cerebral blood flow among sickle cell anemia children.

Background: Stroke is one of the highest complications of sickle-cell anemia (SCA). The Transcranial Doppler (TCD) has been adopted worldwide as a gold standard method for detecting alterations in the blood velocity in cerebral arteries. In this study, we investigated the association between laboratory parameters and increased cerebral blood flow velocity in Brazilian SCA pediatric patients. Methods: The study included 159 pediatric patients with SCA, submitted to TCD velocity screening, and the time-averaged maximum mean velocity (TAMMV) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). We compared cerebral blood flow in patients stratified by the following: TCD1-defined as normal, with TAMMV inferior to 170 cm/s; TCD2-conditional, with TAMMV above 170 cm/s, but less than 199 cm/s; TCD3-altered, with TAMMV greater than or equal to 200 cm/s. Results: TAMMV was negatively correlated with age and weight (p < 0.05). Moreover, TAMMV was associated or correlated with reductions in HbF, RBC, hemoglobin, hematocrit, HDL, and haptoglobin and, increases in MCV, MCH, RDW, reticulocytes, WBC, lymphocytes, monocytes, eosinophils, total and indirect bilirubin, LDH, AST, ALT, glucose, ferritin, and AAT (p < 0.05). Conclusion: The current study highlights the importance of the investigation of hemolytic and inflammatory biomarkers for monitoring the clinical outcome of SCA pediatric patients, to avoid acute or chronic stroke. Moreover, glucose and HDL-C appear useful for predicting higher TAMMV.

Modulation of NF-YB genes in Ricinus communis L. in response to different temperatures and developmental stages and functional characterization of RcNF-YB8 as an important regulator of flowering time in Arabidopsis thaliana.

We have characterized the NF-YB gene family in R. communis using bioinformatics, ecotopic expression, and transcriptomics. A total of 14 RcNF-YB genes were identified in R. communis genome using the conserved NF-YB region. This number is similar to what is found in A. thaliana (13 genes) and O. sativa (11 genes), whereas it is considerably lower to what is found in P. trichocarpa (21 genes) and S. lycopersycum (29 genes). Several regulatory cis-elements were identified in the promoter region, including low temperature, defense and stress, MIC, MYB, and abscisic acid. RcNF-YB is strongly modulated by temperature and it is dependent on the stage of germination. In general, RcNF-YB genes showed higher expression levels in dry seeds and early imbibition (EI) samples as compared to later stages of seedling development. Ectopic expression of RcNF-YB8 reduced flowering time in Arabidopsis reducing the time required for the formation of the first visible bud, the time required to open the first flower, and the time required for the formation of the first visible silique. At the end of the life cycle, ectopic expression of RcNF-YB8 affected plant height (PH), silique length (SL), the total number of silique per plant, 1000-seed weight, and seed size. Our data demonstrated the role of RcNF-YB8 in flowering time, plant height and seed production, and it shows that it may constitute a key target gene for breeding superior R. communis genotypes.

Expanded access with intravenous hydroxypropyl-ß-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis.

BACKGROUND: Niemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPßPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HPßCD has been administered to NPC patients with approved INDs globally since 2009. RESULTS: Here we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7 years with HPßCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPßCD following on average 13 months of IV HPßCD. Several patients transitioned to an alternate HPßCD. Moderately affected NPC patients treated with HPßCD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer. CONCLUSIONS: These expanded access data support the safety and potential benefit of systemic IV administration of HPßCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPßCD in NPC patients.

Laboratory and Genetic Biomarkers Associated with Cerebral Blood Flow Velocity in Hemoglobin SC Disease.

Reference values for cerebral blood flow velocity (CBFV) in hemoglobin SC disease (HbSC) have not been established. We aimed to investigate associations between laboratory and genetic biomarkers associated with CBFV in HbSC children. Sixty-eight HbSC children were included; CBFV was analyzed by transcranial Doppler, and the time-averaged maximum mean velocity (TAMMV) was estimated. Hematological, biochemical, immunological, and genetic analyses were performed. TAMMV was negatively correlated with red blood cell count (RBC) count, hemoglobin, hematocrit, and direct bilirubin (DB), yet positively correlated with monocytes and ferritin. We found that children with TAMMV ≥ 128 cm/s had decreased red blood cell distribution width (RDW) and nitric oxide metabolite (NOx) concentration. Children with TAMMV ≥ 143.50 cm/s had decreased hemoglobin and hematocrit, as well as increased ferritin levels. Decreased hemoglobin, hematocrit, RDW, and NOx and increased ferritin were detected in children with TAMMV ≥ 125.75 cm/s. The CAR haplotype was associated with higher TAMMV. In association analyses, RBC, hemoglobin, hematocrit, RDW, monocyte, DB, NOx, and ferritin, as well as the CAR haplotype, were found to be associated with higher TAMMV in HbSC children. Multivariate analysis suggested that high TAMMV was independently associated with hematocrit, RDW, and NOx. Additional studies are warranted to validate the establishment of a cutoff value of 125.75 cm/s associated with elevated TAMMV in HbSC children.

Comprehensive neuropsychological evaluation of children and adolescents with sickle cell anemia: a hospital-based sample.

BACKGROUND: Individuals with sickle cell anemia may suffer symptomatic or silent cerebral infarcts leading to neurocognitive complications. This study investigated the cognitive and intellectual performance of children and adolescents with sickle cell anemia. METHODS: The socioeconomic status, clinical aspects and behavioral profile of 15 young individuals with sickle cell anemia were evaluated. The Wechsler Intelligence Scale for Children, the Developmental Neuropsychological Assessment Test, and the Child Behavior Checklist were applied. RESULTS: Participants with a history of stroke had lower intelligence quotient (IQ) scores. Alterations were found in attention and executive functioning, language, verbal and visual memory, visuospatial processing and sensorimotor skills. These alterations were found both in the children and adolescents who had had a cerebral infarction and in those who apparently had not. In the majority of cases, there were learning difficulties, a history of repeating school years and a need for specialist educational support. The most common additional diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders IV were depressive disorder, anxiety disorder and somatic disorder, as well as conditions associated with physical and psychosocial repercussions of sickle cell anemia. CONCLUSION: As sickle cell anemia is considered a progressive cerebral vasculopathy, it is a potential risk factor for neurocognitive and psychosocial development. Therefore, periodic neuropsychological and behavioral evaluations of children and adolescents with sickle cell anemia may represent a useful measure to reduce long-term biopsychosocial repercussions.

Comprehensive neuropsychological evaluation of children and adolescents with sickle cell anemia: a hospital-based sample

Abstract Background: Individuals with sickle cell anemia may suffer symptomatic or silent cerebral infarcts leading to neurocognitive complications. This study investigated the cognitive and intellectual performance of children and adolescents with sickle cell anemia. Methods: The socioeconomic status, clinical aspects and behavioral profile of 15 young individuals with sickle cell anemia were evaluated. The Wechsler Intelligence Scale for Children, the Developmental Neuropsychological Assessment Test, and the Child Behavior Checklist were applied. Results: Participants with a history of stroke had lower intelligence quotient (IQ) scores. Alterations were found in attention and executive functioning, language, verbal and visual memory, visuospatial processing and sensorimotor skills. These alterations were found both in the children and adolescents who had had a cerebral infarction and in those who apparently had not. In the majority of cases, there were learning difficulties, a history of repeating school years and a need for specialist educational support. The most common additional diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders IV were depressive disorder, anxiety disorder and somatic disorder, as well as conditions associated with physical and psychosocial repercussions of sickle cell anemia. Conclusion: As sickle cell anemia is considered a progressive cerebral vasculopathy, it is a potential risk factor for neurocognitive and psychosocial development. Therefore, periodic neuropsychological and behavioral evaluations of children and adolescents with sickle cell anemia may represent a useful measure to reduce long-term biopsychosocial repercussions.

Transcranial Doppler in hemoglobin SC disease.

BACKGROUND: Stroke is a severe clinical disorder in sickle cell disease (SCD), and few studies have evaluated transcranial Doppler (TCD) flow velocities in hemoglobin SC disease (HbSC). The guidelines for stroke risk are based on evaluations in sickle cell anemia (SCA) or HbS/ß thalassemia. PROCEDURE: In this study, we compare cerebral blood flow in patients with SCD stratified by genotypes. A total of 1,664 pediatric patients with SCD underwent TCD velocity screening, and the time-averaged maximum mean velocity (TAMM) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). RESULTS: Abnormal velocities were not identified in the ACA; therefore, we only use ICA and MCA velocities. TAMM from the left and right in the ICA and MCA was 134.3 ± 32.0 and 134.4 ± 32.6 cm/s in patients with SCA, and 105.2 ± 20.6 and 104.7 ± 20.0 cm/s in the patients with HbSC, respectively. Mean TAMM between right and left ICA/MCA was 134.5 ± 30.5 cm/s in the SCA group, and 104.9 ± 19.3 cm/s in the HbSC group. Notably, our data show that TCD velocities were significantly lower among the patients with HbSC compared to SCA. TAMM was negatively correlated with hemoglobin and hematocrit in both genotypes. CONCLUSION: These results suggest that a different cut-off value for abnormal TCD velocities could be considered for patients with HbSC. Additional studies are warranted to determine the actual risk of stroke in HbSC genotype associated with this possible TCD risk value.

Prevalence of clliac disease in children with epilesyy / Prevalencia de doenca celiaca em criancas com epilepsia

Context Neurological symptoms have been well-documented in patients with celiac disease, nevertheless, the presumption of a greater prevalence of epilepsy in celiac patients remains controversial. Objectives To determine the frequency of celiac disease in children and adolescents with idiopathic or cryptogenic epilepsy. Methods A cross-sectional study. One hundred pediatric patients with non-symptomatic epilepsy were followed-up at two public pediatric neurology clinics in Salvador, Bahia, Brazil. Screening for celiac disease was performed by serial measurements of IgA anti-transglutaminase and IgA anti-endomysium antibodies, followed by bowel biopsy in positive cases. HLA DQ02 and DQ08 were investigated in seropositive individuals, assessing the type of seizures, the number of antiepileptic drugs used and the presence gastrointestinal symptoms. Results Three (3.0%) patients tested anti-tTG-positive, two with normal duodenal mucosa (Marsh 0) and one with intraepithelial infiltrate (Marsh I). No villous atrophy of the duodenal mucosa (Marsh III) celiac disease was found. Two patients tested positive for HLA DQ02; none were DQ08 positive. Conclusion The present study failed to prove the association between celiac disease and epilepsy. .

Contexto Os sintomas neurológicos têm sido bem documentados em pacientes com doença celíaca, no entanto, a presunção de uma maior prevalência de epilepsia em pacientes celíacos permanece controverso. Objetivos Determinar a frequência de Doença Celíaca em crianças e adolescentes portadores de epilepsia idiopática ou criptogênica. Métodos Estudo transversal. Cem pacientes pediátricos com epilepsia não-sintomática foram acompanhados em dois ambulatórios públicos de neurologia pediátrica em Salvador, Bahia, Brasil. Triagem para doença celíaca foi feita por dosagem sérica de IgA anti-transglutaminase e anti-endomísio IgA, seguido por biópsia de intestino nos casos positivos. HLA DQ02 e DQ08 foram investigadas em indivíduos soropositivos, avaliando o tipo de crise epiléptica, o número de medicamentos anti-epilépticos utilizados e a presença de sintomas gastrointestinais. Resultados Três (3,0%) pacientes apresentaram anti-transglutaminase positivo, dois com mucosa normal duodenal (Marsh 0) e um com infiltrado intraepitelial (Marsh I). Não foi encontrada atrofia das vilosidades da mucosa do duodeno (Marsh III). Dois deles foram positivos para o HLA DQ02; nenhum foi DQ08 positivo. Conclusão O presente estudo não conseguiu provar a associação entre doença celíaca e epilepsia. .

Prevalence of celiac disease in children with epilepsy.

CONTEXT: Neurological symptoms have been well-documented in patients with celiac disease, nevertheless, the presumption of a greater prevalence of epilepsy in celiac patients remains controversial. OBJECTIVES: To determine the frequency of celiac disease in children and adolescents with idiopathic or cryptogenic epilepsy. METHODS: A cross-sectional study. One hundred pediatric patients with non-symptomatic epilepsy were followed-up at two public pediatric neurology clinics in Salvador, Bahia, Brazil. Screening for celiac disease was performed by serial measurements of IgA anti-transglutaminase and IgA anti-endomysium antibodies, followed by bowel biopsy in positive cases. HLA DQ02 and DQ08 were investigated in seropositive individuals, assessing the type of seizures, the number of antiepileptic drugs used and the presence gastrointestinal symptoms. RESULTS: Three (3.0%) patients tested anti-tTG-positive, two with normal duodenal mucosa (Marsh 0) and one with intraepithelial infiltrate (Marsh I). No villous atrophy of the duodenal mucosa (Marsh III) celiac disease was found. Two patients tested positive for HLA DQ02; none were DQ08 positive. CONCLUSION: The present study failed to prove the association between celiac disease and epilepsy.

The importance of methylmalonic acid dosage on the assessment of patients with neurological manifestations following bariatric surgery.

Vitamin B12 or cyanocobalamin is an important substance that is included in several metabolic pathways. Its deficiency is a common event after bariatric surgery, decreasing the vitamin B12 absorption after almost all of the stomach and duodenum are eliminated from the digestion process. Neurological manifestations of cyanocobalamin deficiency are not uncommon. We report a case of a young woman who developed ataxia, weakness and peripheral neuropathy after bariatric surgery, but with normal value of vitamin B12 dosage. For the diagnosis, it was necessary to dose methylmalonic acid. We discuss the importance of methylmalonic acid dosage after bariatric surgery in patients who present suspect of cyanocobalamin deficiency with normal values of this vitamin and the role of proton pump inhibitor use and vitamin supplementation in patients with early neurological presentation.

What do Brazilian pediatricians know about celiac disease?

INTRODUCTION: Celiac disease (CD) is a common illness, affecting 0.5-1% of the population. Its classic presentation consists of gastrointestinal symptoms, however, many extra-intestinal symptoms and some associated diseases have been studied. Pediatricians should know the typical and atypical presentations of CD and how to diagnosis and treat its complications. The aim of this study was describe what pediatricians in Brazil know about CD. METHODS: A descriptive, cross-sectional study with pediatricians who participated in the Nestlé Pediatrics Course, in the city of Natal, Brazil, in 2008. They were asked to complete a self-applicable questionnaire covering aspects concerning the prevalence, diagnosis, and treatment of CD and the conditions associated with this disease. RESULTS: A total of 632 pediatricians completed the questionnaire. The majority of respondents (82.9%) were female. All the geographical regions of Brazil were represented. More than 65% of respondents had undergone specialist training in pediatrics, and 40% of respondents had worked as pediatricians for more than 25 years. Only 22% replied that celiac disease may be asymptomatic, 57% stated that antigliadin antibody measurement represents the best screening tool for the disease, and two-thirds replied that bowel biopsy would be the most indicated method. The pathologies and conditions associated with celiac disease were identified by fewer than 50% of respondents. Exclusion of gluten from the patient's diet was mentioned as the treatment for celiac disease by 86.4% of the pediatricians. CONCLUSIONS: We conclude that pediatricians have superficial information about CD. The need for relevant information on celiac disease is fundamental and is recognized by the pediatricians themselves.

Incidence of diarrhea in children living in urban slums in Salvador, Brazil.

Diarrhea remains a major health issue in developing countries, with high morbidity and mortality rates. Determining the incidence of acute diarrhea in children and its associated factors is crucial to the planning of preventive approaches. The objective of this study was to determine the incidence of diarrhea and to assess some relevant associated factors to it in children younger than 40 months living in two slums of Salvador, Brazil. This is the first prospective cohort, community-based study that was performed in two periurban slums of Salvador, Brazil. Eighty-four children younger than 40 months were randomly selected and visited every other day for one year. The chi-square test was used to evaluate the occurrence of diarrhea and its associated factors. During the surveillance period, 232 diarrhea episodes were identified, resulting in an incidence rate of 2.8 episodes/child/year. In average (mean value of 84 children),each child suffered 11.1 days of diarrhea per year, yielding an average duration of 3.9 days per episode. The highest incidence rates were found among children under one year old. Early weaning, male sex, malnutrition, having a mother younger than 25 years or who considered her child malnourished, missed immunizations and previous pneumonia were associated factors for suffering diarrheal episodes. The rates of incidence and duration of diarrhea that we found are in accordance to those reported by others. Additionally, our results reinforce the importance of environmental and health-related associated factors to the onset of diarrhea.

Incidence of diarrhea in children living in urban slums in Salvador, Brazil

Diarrhea remains a major health issue in developing countries, with high morbidity and mortality rates. Determining the incidence of acute diarrhea in children and its associated factors is crucial to the planning of preventive approaches. The objective of this study was to determine the incidence of diarrhea and to assess some relevant associated factors to it in children younger than 40 months living in two slums of Salvador, Brazil. This is the first prospective cohort, community-based study that was performed in two periurban slums of Salvador, Brazil. Eighty-four children younger than 40 months were randomly selected and visited every other day for one year. The chi-square test was used to evaluate the occurrence of diarrhea and its associated factors. During the surveillance period, 232 diarrhea episodes were identified, resulting in an incidence rate of 2.8 episodes/child/year. In average (mean value of 84 children),each child suffered 11.1 days of diarrhea per year, yielding an average duration of 3.9 days per episode. The highest incidence rates were found among children under one year old. Early weaning, male sex, malnutrition, having a mother younger than 25 years or who considered her child malnourished, missed immunizations and previous pneumonia were associated factors for suffering diarrheal episodes. The rates of incidence and duration of diarrhea that we found are in accordance to those reported by others. Additionally, our results reinforce the importance of environmental and health-related associated factors to the onset of diarrhea.