RESUMO
OBJECTIVE: Huntington's disease (HD) is a neurodegenerative disease caused by a triplet repeat expansion within the gene huntingtin (HTT). Antagonistic pleiotropy is a theory of aging that posits that some genes, facilitating individual fitness early in life through adaptive evolutionary changes, also augment detrimental aging-related processes. Antagonistic pleiotropy theory may explain a positive evolutionary pressure toward functionally advantageous brain development that is vulnerable to rapid degeneration. The current study investigated antagonistic pleiotropy in HD using a years-to-onset paradigm in a unique sample of children and young adults at risk for HD. METHODS: Cognitive, behavioral, motor, and brain structural measures from premanifest gene-expanded (n = 79) and gene nonexpanded (n = 112) participants (6-21 years) in the Kids-HD study were examined. All measures in the gene-expanded group were modeled using a mixed-effects regression approach to assess years-to-onset-based changes while controlling for normal growth. Simultaneously, structure-function associations were also examined. RESULTS: Decades from motor onset, gene-expanded participants showed significantly better cognitive, behavioral, and motor scores versus gene nonexpanded controls, along with larger cerebral volumes and cortical features. After this initial peak, a prolonged deterioration was observed in both functional and structural measures. Far from onset, brain measures were positively correlated with functional measures, supporting the view that functional advantages were mediated by structural differences. INTERPRETATION: Mutant HTT may drive the development of a larger than normal brain that subserves superior early-life function. These findings support the antagonistic pleiotropy theory of HTT in HD, where this gene drives early advantage followed by accelerated aging processes. ANN NEUROL 2024.
RESUMO
BACKGROUND: Within the pediatric population, a positive self-concept is associated with better academic achievement. Children with chronic kidney disease (CKD) are at risk for lower quality of life and academic underachievement. Little is known about self-concept among children with CKD and how self-concept influences academic achievement. The objectives of the present study were to (1) describe patient-reported self-concept among children with CKD and (2) evaluate the relationship between self-concept and academic performance. METHODS: This cross-sectional study included 23 children, aged 6-16 years, with mild to moderate CKD (cause of disease due to congenital anomalies of the kidney and urinary tract) and 26 age-matched comparators. Participants completed the Self-Description Questionnaire (SDQ) and the Wide Range Achievement Test (WRAT-4). Linear regression models were used to evaluate self-concept as a predictor of academic achievement in the CKD cohort. RESULTS: Self-concept ratings were comparable between children with CKD and non-CKD comparators; however, academic achievement trended lower for the CKD patients on measures of arithmetic (estimate = - 0.278, 95% confidence interval (CI) [- 0.530: - 0.026], t(45) = - 1.99, p = 0.053). All of the SDQ domains predicted WRAT-4 arithmetic performance, such that higher scores on the SDQ were associated with higher scores in mathematics. Kidney function did not have an effect on the relationship between self-concept and academic achievement. CONCLUSIONS: Despite the presence of a chronic disease, children with CKD endorse a positive self-concept. Positive self-concept may predict academic success in this population.
Assuntos
Sucesso Acadêmico , Insuficiência Renal Crônica , Humanos , Criança , Qualidade de Vida , Estudos Transversais , Escolaridade , Insuficiência Renal Crônica/epidemiologiaRESUMO
This study evaluated the effectiveness of academic screening measures in relation to parent-reported diagnoses.Multicenter, retrospective cohort study including structured interviews, questionnaires, and chart reviews.Six North American cleft centers.Children (n = 391) with cleft lip and/or palate, ages 8 to 10 years of age (192 male) and their guardians were recruited during regular clinic visits.Parent and child ratings on the Pediatric Quality of Life Inventory (PedsQL) School Scale, child report on CleftQ School Scale, parent report on the Adaptive Behavior Assessment System-Third Edition Functional Academics (ABAS-FA) Scale and Child Behavior Checklist (CBCL) School Competency Scale, parent interview, and medical chart review.Risk for concerns ranged from 12% to 41%, with higher risk reflected on the CBCL-SC compared to other measures. Males with cleft palate were consistently at the highest risk. Only 9% of the sample had a parent-reported diagnosis of a learning or language disability. Ratings from the ABAS-FA and CBCL-SC had the highest utility in identifying those with language and/or learning concerns.As cleft teams work to develop standardized batteries for screening and monitoring of patients, it is important to evaluate the effectiveness of measures in identifying those at highest risk. When screening for language and learning disorders, questions related to potential academic struggles, such as increased school effort or increased school distress, are most useful. Referrals for follow-up evaluation are recommended for those identified at high risk.
Assuntos
Fenda Labial , Fissura Palatina , Criança , Humanos , Masculino , Qualidade de Vida , Estudos Retrospectivos , Estudantes , FemininoRESUMO
BACKGROUND: Pediatric chronic kidney disease (CKD) patients are at risk for cognitive deficits with worsening disease progression. Limited, existing cross-sectional studies suggest that cognitive deficits may improve following kidney transplantation. We sought to assess cognitive performance in relationship to kidney transplantation and kidney-specific medical variables in a sample of pediatric kidney transplant patients who provided cross-sectional and longitudinal observations. METHODS: A retrospective chart review was conducted in patients who completed pre- and/or post-transplant neurocognitive testing at the University of Iowa from 2015-2021. Cognitive outcomes were investigated with developmentally appropriate, standardized measures. Mixed linear models estimated the impact of transplant status on cognitive function (z-scores). Subsequent post-hoc t-tests on change scores were limited to patients who had provided pre- and post-transplant assessments. RESULTS: Thirty eight patients underwent cognitive assessments: 10 had both pre- and post-transplant cognitive assessments, 11 had pre-transplant assessments only, and 17 had post-transplant data only. Post-transplant status was associated with significantly lower full-scale IQ and slower processing speed compared to pre-transplant status (estimate = -0.32, 95% confidence interval [CI] = -0.52: -0.12; estimate = -0.86, CI = -1.17: -0.55, respectively). Post-hoc analyses confirmed results from the mixed models (FSIQ change score = -0.34, 95% CI = -0.56: -0.12; processing speed change score = -0.98, CI = -1.28: -0.68). Finally, being ≥80 months old at transplant was associated with substantially lower FSIQ compared to being <80 months (estimate = -1.25, 95% CI = -1.94: -0.56). CONCLUSIONS: Our results highlight the importance of monitoring cognitive function following pediatric kidney transplant and identify older transplant age as a risk factor for cognitive deficits.
Assuntos
Transplante de Rim , Insuficiência Renal Crônica , Humanos , Criança , Estudos Retrospectivos , Estudos Transversais , Rim , Insuficiência Renal Crônica/complicaçõesRESUMO
This observational, multisite cohort study explored health-related quality of life (HRQoL) in children with cleft lip and/or palate (CL/P), including interrater agreement and ratings for this group relative to clinical cutoff scores and published means for healthy and chronically ill children.Participants (338 children ages 8-10 years, 45.9% male and their parents, 82.0% female) across 6 sites completed the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL).Intraclass correlation revealed poor interrater agreement for most HRQoL domains. Although ratings were generally higher than those expected for children with a chronic illness, child ratings were below healthy means for school functioning, and parent proxy ratings were below healthy means for all domains except physical functioning. Lower ratings consistent with chronic illness means were found for self-reported emotional and psychosocial functioning in children with cleft lip and palate (CLP), as well as parent proxy-reported emotional, school, and psychosocial functioning for children with cleft palate (CP). Scores were most likely to be in the clinical range for children with CP for social, school, and total functioning.Although parent proxy report provides important information about observed functioning, poor interrater agreement indicates that both child and parent proxy reported HRQoL should be included in outcomes assessment for CL/P. HRQoL ratings may be higher for children with CL/P compared to youth with other chronic illnesses, but psychosocial functioning may be negatively impacted when compared with healthy youth, particularly for emotional, social, and school functioning in children with CLP or CP.
Assuntos
Fenda Labial , Fissura Palatina , Adolescente , Criança , Humanos , Masculino , Feminino , Qualidade de Vida/psicologia , Fenda Labial/psicologia , Fissura Palatina/psicologia , Estudos de Coortes , Pais/psicologia , Doença CrônicaRESUMO
OBJECTIVE: To determine associations of demographic, morphologic, and treatment protocol parameters with quality of life (QoL), appearance/speech satisfaction, and psychological adjustment. DESIGN: Observational study utilizing retrospective report of protocol variables and current outcome variables. SETTING: Six North American cleft treatment clinics. PARTICIPANTS: Children, ages 8.0-10.99 years, with Cleft Lip ± Alveolus, Cleft Palate, Cleft Lip and Palate, and parents (N = 284). OUTCOME MEASURES: Pediatric QoL Inventory (PedsQL): Parent, Child, Family Impact Module (FIM); Patient Reported Outcome Measurement Information System (PROMIS); Child Behavior Checklist (CBCL); CLEFT-Q. RESULTS: Outcome scores were average with few differences by cleft type. Multiple regression analyses yielded significant associations (Ps < .05) between socioeconomic status, race, and age at assessment and parent- and self-reported measures. Females had higher PROMIS Depression (ß=.20) but lower CBCL Affective (ß = -.16) and PROMIS Stigma scores (ß= -.24). Incomplete cleft lip was associated with lower PROMIS Depression, and more positive ratings of CLEFT-Q: Nose, Nostril, Lip Scar; CBCL Competence scores, (ßs = -.17 to .17). Younger Age at Lip Closure was associated with higher CBCL School Competence (ß= -.18). Younger Age at Palate Closure was associated with higher Child PedsQL Total, Physical, Psychosocial QoL, and better CLEFT-Q Speech Function (ßs = -.18 to -.15). Furlow Palatoplasty was associated with more CBCL Externalizing Problems (ß = .17) higher CBCL Activities (ß = .16). For all diagnoses, fewer Total Cleft-Related Surgeries was associated with lower PROMIS Stigma and higher CBCL Total Competence and Activities (ßs = -.16 to .15). CONCLUSIONS: Demographic characteristics, lip morphology, and treatment variables are related to later psychological functioning.
RESUMO
OBJECTIVE: To assess sex-specific differences in early brain structure and function of preterm infants after red blood cell (RBC) transfusions. STUDY DESIGN: A single-center subset of infants with a birth weight <1000 g and gestational age 22-29 weeks were enrolled from the National Institute of Child Health and Human Development's Neonatal Research Network Transfusion of Prematures Trial. Hemoglobin (Hb) concentration obtained directly before each transfusion (pretransfusion Hb [ptHb]) was obtained longitudinally throughout each infant's neonatal intensive care unit stay and used as a marker of degree of anemia (n = 97). Measures of regional brain volumes using magnetic resonance imaging were obtained at â¼40 weeks postmenstrual age or at hospital discharge, if earlier (n = 29). Measures of brain function were obtained at 12 months corrected age using the Bayley Scales of Infant & Toddler Development, 3rd Edition (n = 34). RESULTS: PtHb was positively correlated with neonatal cerebral white matter volume in males (B = +0.283; P = .006), but not females (B = -0.099; P = .713), resulting in a significant sex interaction (P = .010). Bayley-III gross motor scores and a pooled mean score were significantly lower in association with higher ptHb in females (gross motor score: B = -3.758; P = .013; pooled mean score: B = -1.225; P = .030), but not males (gross motor score: B = +1.758; P = .167; pooled mean score: B = +0.621; P = .359). Higher ptHb was associated with descriptively lower performance on multiple Bayley-III subscales in females, but not in males. CONCLUSIONS: This study demonstrates sex-specific associations between an early marker of anemia and RBC transfusion status (ie, ptHb) with both neonatal white matter volume and early cognitive function at age 12 months in preterm infants.
Assuntos
Recém-Nascido Prematuro , Caracteres Sexuais , Encéfalo/patologia , Desenvolvimento Infantil , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Limited data exists regarding the disease course of Huntington's Disease (HD) in children and young adults. Here, we evaluate the trajectory of various cognitive skill development as a function of cytosine-adenine-guanine (CAG) repeat length in children and adolescents that carry the mutation that causes HD. We discovered that the development of verbal skills seems to plateau earlier as CAG repeat length increases. These findings increase our understanding of the relationship between neurodegeneration and neurodevelopment and may have far-reaching implications for future gene-therapy treatment strategies. ANN NEUROL 2021;89:1036-1040.
Assuntos
Envelhecimento/psicologia , Cognição/fisiologia , Proteína Huntingtina/genética , Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Criança , Função Executiva , Feminino , Heterozigoto , Humanos , Desenvolvimento da Linguagem , Estudos Longitudinais , Masculino , Mutação , Testes Neuropsicológicos , Comportamento Verbal , Percepção Visual , Adulto JovemRESUMO
BACKGROUND: Children with isolated cleft of the lip and/or palate (iCL/P) are at a higher risk for language and reading issues. The current pilot study evaluated concurrent writing skills of children with iCL/P compared to unaffected participants with average (uAR) and impaired (uIR) reading. It was hypothesized that children with iCL/P would perform lower than age-expectations. METHODS: Twenty-three males, aged 8-11 years old, were recruited through clinics, local advertisements, and state dyslexia groups (iCL/P = 7, uAR = 8, uIR = 8). Group differences on measures of cognitive processes and writing were evaluated using ANCOVA. Relationships between these measures were compared for each group through Pearson correlations. RESULTS: Participants with iCL/P performed within the average range across all measures; group differences were only found for the uIR group. For those with iCL/P, writing was correlated to global cognitive skills rather than more specific skills. CONCLUSIONS: While this small sample of children with iCL/P demonstrated average writing skills, patterns suggest performance is related to global cognitive reasoning rather than specific cognitive processes as found in unaffected children with impaired reading. Further research is needed to better understand writing in iCL/P and the relationship to reading and cognitive processes. IMPACT: Research in children with isolated cleft of the lip and/or palate (iCL/P) has demonstrated higher rates of language and reading disorders. No work has assessed written expression in children with iCL/P in over 40 years. This study is the first to evaluate elements of written expression and associated cognitive processes among children with iCL/P in comparison to unaffected children with either average or impaired reading skills. Measures of writing were within the average range for children with iCL/P and demonstrated correlation to global cognitive reasoning rather than to specific cognitive processes as found in unaffected children with impaired reading.
Assuntos
Fenda Labial , Fissura Palatina , Criança , Fenda Labial/psicologia , Fissura Palatina/psicologia , Humanos , Idioma , Masculino , Projetos Piloto , RedaçãoRESUMO
BACKGROUND: The purpose of this research study was to evaluate the earliest markers of vocal functioning and neurological development in infants with isolated oral cleft of the lip and/or palate (iCL/P). METHODS: Participants were recruited through advertisements and clinic visits at a local mid-western university. A total of eight participants (four unaffected and four with iCL/P), ranging in age from 7.29 to 11.57 weeks, were enrolled and completed demographic and pre-speech measures. A subset of six males (four unaffected and two with iCL/P) successfully completed a structural magnetic resonance imaging scan. RESULTS: Patterns of disrupted vocal control and reduced myelinated white matter were found in participants with iCL/P. CONCLUSIONS: The findings of this study provide a foundation from which to build further research on the neuronal development of infants with oral clefts: the need to evaluate measures of cortical development, inclusion of information on anesthesia exposure and airway obstruction, and suggestions for avoiding identified pitfalls/blocks to obtaining data are discussed. IMPACT: Research in children with isolated oral clefts has demonstrated higher rates of learning disorders connected to subtle differences in brain structure. There is no work evaluating the potential impact of exposure to anesthesia on development. This is the first known attempt to evaluate brain structure and function in infants with isolated oral clefts before exposure to anesthesia. Potential trends of early vocal issues and structural brain differences (less myelinated white matter) were identified in infants with isolated oral clefts compared to unaffected controls. Differences in brain structure and function in infants with isolated oral clefts may be present before surgery.
Assuntos
Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil , Fenda Labial/fisiopatologia , Fenda Labial/psicologia , Fissura Palatina/fisiopatologia , Fissura Palatina/psicologia , Choro , Comportamento do Lactente , Comportamento Verbal , Acústica , Fatores Etários , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Espectrografia do Som , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimentoRESUMO
BACKGROUND: The impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early-stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI). METHODS: The sample age range was 6-16 years. A total of 18 children with a diagnosis of pCKD (CKD stages 1-3) due to congenital anomalies of the kidney and urinary tract and 24 typically developing peers were included. Volumetric data from MRI and neurocognitive testing were compared using linear models including pCKD status, age, maternal education level, and socioeconomic status. RESULTS: Cerebellar gray matter volume was significantly smaller in pCKD, t(38) = -2.71, p = 0.01. In contrast, cerebral gray matter volume was increased in pCKD, t(38) = 2.08, p = 0.04. Reduced cerebellum gray matter volume was associated with disease severity, operationalized as estimated glomerular filtration rate (eGFR), t(14) = 2.21, p = 0.04 and predicted lower verbal fluency scores in the pCKD sample. Enlarged cerebral gray matter in the pCKD sample predicted lower scores on mathematics assessment. CONCLUSIONS: This study provides preliminary evidence for a morphometric underpinning to the cognitive deficits observed in pCKD. IMPACT: The impact of pediatric chronic kidney disease (CKD) on the brain remains poorly defined, with no data linking brain morphometry and observed cognitive deficits noted in this population. We explored the relationship between brain morphometry (using structural magnetic resonance imaging), cognition, and markers of CKD. Cerebellar and cerebral gray matter volumes are different in early CKD. Volumetric decreases in cerebellar gray matter are predicted by lower eGFR, suggesting a link between disease and brain morphometry. Reduced cerebellar gray matter predicted lower verbal fluency for those with pCKD. Enlarged cerebral gray matter in the pCKD sample predicted lower mathematics performance.
Assuntos
Substância Cinzenta/patologia , Transtornos Neurocognitivos/etiologia , Insuficiência Renal Crônica/patologia , Adolescente , Cerebelo/patologia , Cérebro/patologia , Criança , Escolaridade , Feminino , Taxa de Filtração Glomerular , Substância Cinzenta/diagnóstico por imagem , Humanos , Rim/anormalidades , Imageamento por Ressonância Magnética , Masculino , Matemática , Mães/educação , Transtornos Neurocognitivos/diagnóstico por imagem , Neuroimagem , Tamanho do Órgão , Projetos Piloto , Insuficiência Renal Crônica/complicações , Classe Social , Distúrbios da Fala/diagnóstico por imagem , Distúrbios da Fala/etiologia , Sistema Urinário/anormalidadesRESUMO
OBJECTIVE: The purpose of this study was to evaluate possible relationships between number of surgeries and parent ratings of academic functioning among children with isolated oral clefts. DESIGN: Multicenter, retrospective cohort study including structured interviews, questionnaires, and chart reviews. SETTING: Completion of questionnaires occurred during clinical visits at 6 different cleft centers across North America. PARTICIPANTS: Parents of 285 children with isolated clefts of the lip and/or palate, aged 8 to 10 years old, participated in structured interviews and completed questionnaires regarding the academic and behavioral functioning of their children. MAIN OUTCOME MEASURES: Parent interview and medical chart review of number of surgeries to date and parent ratings on the Adaptive Behavior Assessment System, Third Edition-Functional Academics Scale (ABAS-FA) and Child Behavior Checklist (CBCL) Total Competency Scale. RESULTS: Parent ratings of ABAS-FA were at or above normative expectations, while ratings across CBCL Competency Scales were lower than normative expectations. Socioeconomic status (SES), age, and race were consistent predictors of parent ratings (higher SES, older age, and Caucasian race were associated with better functioning). Number of surgeries did not add significantly to academic ratings but did significantly contribute to ratings of social and activity participation. Patients with more surgeries were rated with lower functioning in these domains. CONCLUSIONS: Findings do not support a connection between number of surgeries and later ratings of academic functioning but do support a connection to social and activity involvement. Recommendations for conducting direct studies of the connection between surgeries and academic functioning as well as clinical considerations for surgeries and impact on social and activity involvement are discussed.
Assuntos
Fissura Palatina , Idoso , Criança , Fissura Palatina/cirurgia , Humanos , Pais , Estudos Retrospectivos , Classe Social , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The focus of this study was to determine if there is any significant difference in academic achievement for girls and boys with a cleft compared to the general population of Swedish students at graduation from compulsory school. DESIGN: A retrospective population-based study using data obtained from the Swedish Medical Birth Register that was linked to the Swedish School-Grade Register. PARTICIPANTS: Two hundred seventy girls and 241 boys with cleft palate (CP), 222 girls and 429 boys with cleft lip (CL), and 299 girls and 531 boys with cleft lip and palate (CLP) were compared with the compulsory school population comprising 609,397 girls and 640,007 boys. MAIN OUTCOME MEASURES: (1) Odds of receiving the lowest grade and reduced odds in receiving high grades in Mathematics, English, and Swedish. (2) grade point average (GPA). RESULTS: In all 3 subject grades, for boys with cleft there was no difference when compared to the male population. Girls with cleft were similar to their peers with a few exceptions. Girls with CLP had lower Math grades, and girls with CP had lower Math, English, and Swedish grades. Girls with CP and CLP achieved a significantly lower GPA in comparison to the female population and boys with CP and CL achieved lower GPAs in comparison to the male population. CONCLUSIONS: This study indicates that educational outcomes for girls with cleft are more negatively affected than for boys with cleft.
Assuntos
Sucesso Acadêmico , Fenda Labial , Fissura Palatina , Adolescente , Criança , Feminino , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , SuéciaRESUMO
Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain. Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease. © 2016 Wiley Periodicals, Inc.
Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Proteína Huntingtina/genética , Inteligência/genética , Caracteres Sexuais , Repetições de Trinucleotídeos/genética , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Feminino , Humanos , Doença de Huntington/diagnóstico por imagem , Doença de Huntington/genética , Doença de Huntington/patologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Adulto JovemRESUMO
BACKGROUND: Late preterm birth (34-36 wk gestation) is a common occurrence with potential for altered brain development. METHODS: This observational cohort study compared children at age 6-13 y based on the presence or absence of the historical risk factor of late preterm birth. Children completed a battery of cognitive assessments and underwent magnetic resonance imaging of the brain. RESULTS: Late preterm children (n = 52) demonstrated slower processing speed (P = 0.035) and scored more poorly in visual-spatial perception (P = 0.032) and memory (P = 0.007) than full-term children (n = 74). Parents of late preterm children reported more behavioral difficulty (P = 0.004). There were no group differences in cognitive ability or academic achievement. Imaging revealed similar intracranial volumes but less total tissue and more cerebrospinal fluid (P = 0.004) for late preterm children compared to full-term children. The tissue difference was driven by differences in the cerebrum (P = 0.028) and distributed across cortical (P = 0.051) and subcortical tissue (P = 0.047). Late preterm children had a relatively smaller thalamus (P = 0.012) than full-term children. Only full-term children demonstrated significant decreases in cortical tissue volume (P < 0.001) and thickness (P < 0.001) with age. CONCLUSION: Late preterm birth may affect cognition, behavior, and brain structure well beyond infancy.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Recém-Nascido Prematuro , Adolescente , Antropometria , Criança , Cognição , Transtornos Cognitivos , Estudos de Coortes , Deficiências do Desenvolvimento/etiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Destreza Motora , Tamanho do Órgão , Fatores de RiscoRESUMO
The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time.
Assuntos
Transtornos Cognitivos/etiologia , Diabetes Mellitus Tipo 1/complicações , Afeto , Criança , Pré-Escolar , Função Executiva/fisiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Índice Glicêmico , Humanos , Masculino , Testes NeuropsicológicosRESUMO
Introduction: Medical curricula implicitly teach that race has a biological basis. Clinical rotations reinforce this misconception as race-based algorithms are used to guide clinical decision-making. This module aims to expose the fallacy of race in clinical algorithms, using the estimated glomerular filtration rate (eGFR) equation as an example. Methods: We created a 60-minute module in consultation with nephrologists. The format was an interactive, case-based presentation with a didactic section. A third-year medical student facilitated the workshops to medical students. Evaluation included pre/post surveys using 5-point Likert scales to assess awareness regarding use of race as a biological construct. Higher scores indicated increased awareness. Results: Fifty-five students participated in the module. Pre/post results indicated that students significantly improved in self-perceived knowledge of the history of racism in medicine (2.6 vs. 3.2, p < .001), awareness of race in clinical algorithms (2.7 vs. 3.7, p < .001), impact of race-based eGFR on quality of life/treatment outcomes (4.5 vs. 4.8, p = .01), differences between race and ancestry (3.7 vs. 4.3, p < .001), and implications of not removing race from the eGFR equation (2.7 vs. 4.2, p < .001). Students rated the workshops highly for quality and clarity. Discussion: Our module expands on others' work to expose the fallacy of race-based algorithms and define its impact on health equity. Limitations include a lack of objective assessment of knowledge acquisition. We recommend integrating this module into preclinical and clinical curricula to discuss the use of race in medical literature and clinical practice.
Assuntos
Algoritmos , Currículo , Taxa de Filtração Glomerular , Estudantes de Medicina , Humanos , Estudantes de Medicina/estatística & dados numéricos , Estudantes de Medicina/psicologia , Taxa de Filtração Glomerular/fisiologia , Inquéritos e Questionários , Grupos Raciais/estatística & dados numéricos , Educação de Graduação em Medicina/métodos , Masculino , Racismo , FemininoRESUMO
OBJECTIVES: To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function. DESIGN: Observational follow-up of infants with birth weights <1000 g and gestational ages 22-28 weeks who were enrolled in the NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial at 19 U.S. sites, 2012-2017. MAIN OUTCOME MEASURES: Pretransfusion haemoglobin values were obtained longitudinally through 36 weeks' postmenstrual age. The infant's mean pretransfusion haemoglobin was used as a marker of degree of anaemia (n=1655 measures). Measures of brain function were obtained at 22-26 months' corrected age using the Bayley Scales of Infant & Toddler Development, third edition (BSID-III) (n=1290 BSID-III scores). Sex-specific estimates for the linear relation between pretransfusion haemoglobin and BSID-III scores were obtained from repeated-measures regression analysis, adjusted for gestational age, birth weight, study site, clinical characteristics, and demographic covariates. RESULTS: The relation of pretransfusion haemoglobin with 24-month BSID-III scores showed significant, independent interactions with both (1) sex (p=0.046) and (2) retinopathy of prematurity (ROP; p=0.004). In 614 males, BSID-III scores were higher by 1.07 points per g/dL (95% CI 1.58 to 4.33; p=0.008), not differing significantly among the three subscales (cognitive, language and motor; p=0.94). In 247 infants with ROP, BSID-III scores were higher by 2.95 points per g/dL (95% CI 0.28 to 1.87; p<0.0001), uniformly across subscales (p=0.73). These associations were non-significant in 676 females (p=0.96) and 1043 infants without ROP (p=0.81). CONCLUSIONS: This study demonstrates sex-specific associations between mean pretransfusion haemoglobin (a marker of the severity of anaemia throughout the neonatal intensive care unit [NICU] hospitalisation) and early neurodevelopmental function at 22-26 months' corrected age.
Assuntos
Cognição , Hemoglobinas , Recém-Nascido Prematuro , Humanos , Feminino , Masculino , Hemoglobinas/análise , Hemoglobinas/metabolismo , Recém-Nascido , Recém-Nascido Prematuro/sangue , Cognição/fisiologia , Fatores Sexuais , Lactente , Idade Gestacional , Desenvolvimento Infantil/fisiologia , Seguimentos , Pré-Escolar , Anemia/sangueRESUMO
Isolated cleft lip and/or palate (ICLP) is one of the most common congenital birth defects in the USA, affecting roughly 1 in 600 births annually. Along with the facial deformity, this population has been found to have abnormal neurodevelopment and gross structural abnormalities in the brain, particularly within the cerebellum. The current study examined cerebellar structure within the two primary subtypes of ICLP: cleft lip with/without cleft palate (CL/P) and cleft palate alone (CPO). A large sample of 107 subjects aged 7 to 27 years with ICLP was compared to 127 healthy controls. Samples were separated by sex. Brain structure was obtained via magnetic resonance imaging. For males, after controlling for intracranial volume, cerebellum volume was significantly lower in the ICLP group (F = 12.351, p = 0.001). Regionally in the cerebellum, males with ICLP had proportionally larger anterior lobes (F = 4.022, p = 0.047) and smaller superior posterior lobes (F = 5.686, p = 0.019). CL/P males showed only a reduction in overall cerebellum volume, with no regional changes. CPO males showed only regional changes, with no reduction in overall volume. Females with ICLP showed no overall or regional cerebellar abnormalities. However, females with CPO did have significantly lower cerebellum volumes than controls. The results reveal both global and regional cerebellar abnormalities within subjects with ICLP. They also establish the existence of abnormal cerebellar morphologies that are dependent on cleft subtype as well as sex. This lends further support to the claim that CL/P and CPO are distinct conditions.
Assuntos
Cerebelo/anormalidades , Fenda Labial/patologia , Fenda Labial/fisiopatologia , Fissura Palatina/patologia , Fissura Palatina/fisiopatologia , Adolescente , Adulto , Análise de Variância , Cerebelo/patologia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Fenótipo , Fatores Sexuais , Adulto JovemRESUMO
Individuals with nonsyndromic cleft lip with or without cleft palate (CL/P) have altered brain structure compared with healthy controls. Preliminary evidence suggests that the corpus callosum may be dysmorphic in orofacial clefting; however, this midline brain structure has not been systematically assessed in this population. The goal of the present study was to carry out a morphometric assessment of the corpus callosum and its relationship to cognitive performance in a well-characterized patient cohort with orofacial cleft. Midline brain images were obtained from previously collected MRI scans of 24 CL/P subjects and 40-adult-male controls. Eight landmarks on the corpus callosum were digitized on each image and their x,y coordinate locations saved. A geometric morphometrics analysis was applied to the landmark coordinate data to test for shape differences across groups. The relationship between corpus callosum shape and IQ was explored with nonparametric correlation coefficients. Results revealed significant differences in mean corpus callosum shape between CL/P cases and controls (P = 0.029). The CL/P corpus callosum was characterized by increased overall convexity resulting from a superior and posterior displacement. Within CL/P cases, increased corpus callosum shape dysmorphology was moderately correlated with reduced performance IQ (r = 0.546). These results provide additional evidence that midline brain changes may be an important part of the orofacial cleft phenotype.