RESUMO
INTRODUCTION: The aim of the present study was to evaluate fetal umbilical artery (UA) and middle cerebral artery (MCA) blood flow in patients with gestational diabetes (GD), in order to determine whether minimal anomalies of glucose metabolism may influence fetal placental function. METHODS: UA and MCA flows were prospectively measured by transabdominal ultrasound in singleton pregnancies between 34 and 37 weeks of gestation. RESULTS: The study included 35 women with GD and 217 nondiabetic patients. Middle cerebral pulsatility index (PI) was significantly higher in the GD group (mean MCA-PI = 1.82 ± 0.27 vs. 1.71 ± 0.26; p < 0.02). Likewise, MCA peak systolic velocity (MCA-PSV) was higher in the GD group compared to the non-GD group, though the difference was not significant (mean of MCA-PSV = 47.14 ± 8.45 vs. 47.09 ± 11.21; p = 0.98). UA-PI resulted higher in the non-GD group without significant differences (mean of UA-PI = 0.88 ± 0.14 vs. 0.86 ± 0.15; p = 0.32). CONCLUSIONS: Our study shows that even in cases of minimal metabolic derangements, GD is characterized by a significant variation in fetal Doppler velocimetry, particularly in the brain.
Assuntos
Diabetes Gestacional , Artéria Cerebral Média , Velocidade do Fluxo Sanguíneo , Diabetes Gestacional/diagnóstico por imagem , Feminino , Idade Gestacional , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Placenta , Gravidez , Fluxo Pulsátil , Reologia , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Artérias Umbilicais/diagnóstico por imagemRESUMO
Motion perception deficits in dyslexia show a large intersubjective variability, partly reflecting genetic factors influencing brain architecture development. In previous work, we have demonstrated that dyslexic carriers of a mutation of the DCDC2 gene have a very strong impairment in motion perception. In the present study, we investigated structural white matter alterations associated with the poor motion perception in a cohort of twenty dyslexics with a subgroup carrying the DCDC2 gene deletion (DCDC2d+) and a subgroup without the risk variant (DCDC2d-). We observed significant deficits in motion contrast sensitivity and in motion direction discrimination accuracy at high contrast, stronger in the DCDC2d+ group. Both motion perception impairments correlated significantly with the fractional anisotropy in posterior ventral and dorsal tracts, including early visual pathways both along the optic radiation and in proximity of occipital cortex, MT and VWFA. However, the DCDC2d+ group showed stronger correlations between FA and motion perception impairments than the DCDC2d- group in early visual white matter bundles, including the optic radiations, and in ventral pathways located in the left inferior temporal cortex. Our results suggest that the DCDC2d+ group experiences higher vulnerability in visual motion processing even at early stages of visual analysis, which might represent a specific feature associated with the genotype and provide further neurobiological support to the visual-motion deficit account of dyslexia in a specific subpopulation.
Assuntos
Dislexia , Percepção de Movimento , Substância Branca , Dislexia/diagnóstico por imagem , Dislexia/genética , Humanos , Proteínas Associadas aos Microtúbulos , Lobo Occipital , Vias Visuais , Percepção Visual , Substância Branca/diagnóstico por imagemRESUMO
Although it is clear that early language acquisition can be a target of CNTNAP2, the pathway between gene and language is still largely unknown. This research focused on the mediation role of rapid auditory processing (RAP). We tested RAP at 6 months of age by the use of event-related potentials, as a mediator between common variants of the CNTNAP2 gene (rs7794745 and rs2710102) and 20-month-old language outcome in a prospective longitudinal study of 96 Italian infants. The mediation model examines the hypothesis that language outcome is explained by a sequence of effects involving RAP and CNTNAP2. The ability to discriminate spectrotemporally complex auditory frequency changes at 6 months of age mediates the contribution of rs2710102 to expressive vocabulary at 20 months. The indirect effect revealed that rs2710102 C/C was associated with lower P3 amplitude in the right hemisphere, which, in turn, predicted poorer expressive vocabulary at 20 months of age. These findings add to a growing body of literature implicating RAP as a viable marker in genetic studies of language development. The results demonstrate a potential developmental cascade of effects, whereby CNTNAP2 drives RAP functioning that, in turn, contributes to early expressive outcome.
Assuntos
Percepção Auditiva/fisiologia , Desenvolvimento da Linguagem , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Pré-Escolar , Potenciais Evocados P300/fisiologia , Feminino , Genótipo , Humanos , Lactente , Estudos Longitudinais , Masculino , Polimorfismo de Nucleotídeo Único , Estudos ProspectivosRESUMO
Developmental dyslexia (DD) is a complex heritable condition characterized by impaired reading abilities. Two well-replicated candidate risk factors are as follows: (1) regulatory element associated with dyslexia 1 (READ1), which is located in intron 2 of DCDC2 and acts as a binding site for protein regulation of DCDC2 expression; and (2) a three-single-nucleotide polymorphism risk haplotype spanning KIAA0319. Phylogenetically similar READ1 variants showed synergistic effects with the KIAA0319 risk haplotype on reading-related phenotypes in a general population sample. Here we examine the association between different allele classes in READ1, the KIAA0319 risk haplotype and reading-related traits in a cohort of 368 Italian children with DD and their siblings (n=266) by testing both main and non-additive effects. We replicated the deleterious main effects upon both reading accuracy and speed exerted by the longer READ1 alleles. We further supported the interdependence through non-additive, possibly antagonistic, effects between READ1 and the KIAA0319 risk haplotype on reading accuracy. By suggesting the presence of common biological processes underlying reading (dis)ability, these findings represent initial support for a generalist effect of the non-additive interdependence between READ1 and the KIAA0319 risk haplotype. Moreover, our results confirm that using as much information as possible about genetic interdependence among dyslexia-candidate genes can help in clinically assessing the individual risk for DD.
Assuntos
Dislexia/genética , Predisposição Genética para Doença , Proteínas Associadas aos Microtúbulos/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Criança , Dislexia/epidemiologia , Dislexia/patologia , Feminino , Estudos de Associação Genética , Haplótipos , Humanos , Íntrons/genética , Itália/epidemiologia , Masculino , Elementos Reguladores de Transcrição/genética , Fatores de RiscoRESUMO
BACKGROUND: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are among the most common neurodevelopmental disorders, whose etiology involves multiple risk factors. DD and ADHD co-occur in the same individuals much more often than would be expected by chance. Several studies have found significant bivariate heritability, and specific genes associated with either DD or ADHD have been investigated for association in the other disorder. Moreover, there are likely to be gene-by-gene and gene-by-environment interaction effects (G × G and G × E, respectively) underlying the comorbidity between DD and ADHD. We investigated the pleiotropic effects of 19 SNPs spanning five DD genes (DYX1C1, DCDC2, KIAA0319, ROBO1, and GRIN2B) and seven DD environmental factors (smoke, miscarriage, birth weight, breastfeeding, parental age, socioeconomic status, and parental education) for main, either (a) genetic or (b) environmental, (c) G × G, and (d) G × E upon inattention and hyperactivity/impulsivity. We then attempted replication of these findings in an independent twin cohort. METHODS: Marker-trait association was analyzed by implementing the Quantitative Transmission Disequilibrium Test (QTDT). Environmental associations were tested by partial correlations. G × G were investigated by a general linear model equation and a family-based association test. G × E were analyzed through a general test for G × E in sib pair-based association analysis of quantitative traits. RESULTS: DCDC2-rs793862 was associated with hyperactivity/impulsivity via G × G (KIAA0319) and G × E (miscarriage). Smoke was significantly correlated with hyperactivity/impulsivity. We replicated the DCDC2 × KIAA0319 interaction upon hyperactivity/impulsivity in the twin cohort. CONCLUSIONS: DD genetic (DCDC2) and environmental factors (smoke and miscarriage) underlie ADHD traits supporting a potential pleiotropic effect.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Epistasia Genética/genética , Interação Gene-Ambiente , Pleiotropia Genética/genética , Proteínas Associadas aos Microtúbulos/genética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Comorbidade , Dislexia/epidemiologia , Dislexia/etiologia , Dislexia/genética , Feminino , Humanos , Itália/epidemiologia , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage- or brain area-specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts.
RESUMO
Dyslexia is a specific impairment in reading that affects 1 in 10 people. Previous studies have failed to isolate a single cause of the disorder, but several candidate genes have been reported. We measured motion perception in two groups of dyslexics, with and without a deletion within the DCDC2 gene, a risk gene for dyslexia. We found impairment for motion particularly strong at high spatial frequencies in the population carrying the deletion. The data suggest that deficits in motion processing occur in a specific genotype, rather than the entire dyslexia population, contributing to the large variability in impairment of motion thresholds in dyslexia reported in the literature.
Assuntos
Dislexia/diagnóstico , Dislexia/genética , Deleção de Genes , Proteínas Associadas aos Microtúbulos/genética , Percepção de Movimento/fisiologia , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/genética , Adolescente , Dislexia/epidemiologia , Feminino , Humanos , Masculino , Transtornos da Percepção/epidemiologia , Estimulação Luminosa/métodos , Adulto JovemRESUMO
Developmental dyslexia (DD) is a heritable neurodevelopmental reading disorder that could arise from auditory, visual, and cross-modal integration deficits. A deletion in intron 2 of the DCDC2 gene (hereafter DCDC2d) increases the risk for DD and related phenotypes. In this study, first we report that illusory visual motion perception-specifically processed by the magnocellular-dorsal (M-D) stream-is impaired in children with DD compared with age-matched and reading-level controls. Second, we test for the specificity of the DCDC2d effects on the M-D stream. Children with DD and DCDC2d need significantly more contrast to process illusory motion relative to their counterpart without DCDC2d and to age-matched and reading-level controls. Irrespective of the genetic variant, children with DD perform normally in the parvocellular-ventral task. Finally, we find that DCDC2d is associated with the illusory motion perception also in adult normal readers, showing that the M-D deficit is a potential neurobiological risk factor of DD rather than a simple effect of reading disorder. Our findings demonstrate, for the first time, that a specific neurocognitive dysfunction tapping the M-D stream is linked with a well-defined genetic susceptibility.
Assuntos
Dislexia , Deleção de Genes , Ilusões/genética , Íntrons/genética , Proteínas Associadas aos Microtúbulos/deficiência , Percepção de Movimento/fisiologia , Transtornos da Percepção/etiologia , Estudos de Casos e Controles , Criança , Dislexia/complicações , Dislexia/genética , Dislexia/patologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Testes Neuropsicológicos , Transtornos da Percepção/genética , Estimulação LuminosaRESUMO
BACKGROUND: The phenotypic and genetic associations between decoding skills and ADHD dimensions have been documented but less is known about the association with reading comprehension. The aim of the study is to document the phenotypic and genetic associations between reading comprehension and ADHD dimensions of inattention and hyperactivity/impulsivity in early schooling and compare them to those with decoding skills. METHODS: Data were collected in two population-based samples of twins (Quebec Newborn Twin Study - QNTS) and singletons (Quebec Longitudinal Study of Child Development - QLSCD) totaling ≈ 2300 children. Reading was assessed with normed measures in second or third grade. Teachers assessed ADHD dimensions in kindergarten and first grade. RESULTS: Both decoding and reading comprehension were correlated with ADHD dimensions in a similar way: associations with inattention remained after controlling for the other ADHD dimension, behavior disorder symptoms and nonverbal abilities, whereas associations with hyperactivity/impulsivity did not. Genetic modeling showed that decoding and comprehension largely shared the same genetic etiology at this age and that their associations with inattention were mostly explained by shared genetic influences. CONCLUSION: Both reading comprehension and decoding are uniquely associated with inattention through a shared genetic etiology.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Compreensão/fisiologia , Fenótipo , Leitura , Percepção da Fala/fisiologia , Criança , Pré-Escolar , Doenças em Gêmeos , Feminino , Humanos , Masculino , Quebeque , Percepção da Fala/genéticaRESUMO
Both genetic and socio-demographic factors influence the risk for behavioral problems in the developmental age. Genetic studies indicate that shared genetic factors partially contribute to behavioral and learning problems, in particular reading disabilities (RD). For the first time, we explore the conjoint role of DCDC2 gene, an identified RD candidate gene, and socioeconomic status (SES) upon behavioral phenotypes in a general population of Italian children. Two of the most replicated DCDC2 markers [i.e., regulatory element associated with dyslexia 1 (READ1), rs793862] were genotyped in 631 children (boys = 314; girls = 317) aged 11-14 years belonging to a community-based sample. Main and interactive effects were tested by MANOVA for each combination of DCDC2 genotypes and socioeconomic status upon emotional and behavioral phenotypes, assessed by Child Behavior Check-List/6-18. The two-way MANOVA (Bonferroni corrected p value = 0.01) revealed a trend toward significance of READ1(4) effect (F = 2.39; p = 0.016), a significant main effect of SES (F = 3.01; p = 0.003) and interactive effect of READ1(4) × SES (F = 2.65; p = 0.007) upon behavioral measures, showing higher attention problems scores among subjects 'READ1(4+) and low SES' compared to all other groups (p values range 0.00003-0.0004). ANOVAs stratified by gender confirmed main and interactive effects among girls, but not boys. Among children exposed to low socioeconomic level, READ1 genetic variant targets the worst outcome in children's attention.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Dislexia/genética , Interação Gene-Ambiente , Proteínas Associadas aos Microtúbulos/genética , Classe Social , Meio Social , Adolescente , Alelos , Atenção/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Emoções , Etnicidade/genética , Feminino , Variação Genética , Genótipo , Humanos , Testes de Linguagem , Deficiências da Aprendizagem/genética , Masculino , LeituraRESUMO
It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Interação Gene-Ambiente , Receptores de N-Metil-D-Aspartato/genética , Classe Social , Populações Vulneráveis/estatística & dados numéricos , Criança , Feminino , Humanos , Itália , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.
Assuntos
Cromossomos Humanos Par 6/genética , Dislexia/genética , Transtornos da Linguagem/genética , Moléculas de Adesão Celular , Criança , Colorado , Proteínas de Ligação a DNA , Loci Gênicos , Genótipo , Haplótipos , Humanos , Testes de Inteligência , Iowa , Itália , Desequilíbrio de Ligação , Estudos Longitudinais , Proteínas Associadas aos Microtúbulos/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Fenótipo , Diester Fosfórico Hidrolases , Proteínas/genética , Pseudogenes , Testes Psicológicos , Leitura , Tioléster Hidrolases/genética , Fatores de Transcrição/genéticaRESUMO
Substantial heritability has been reported for developmental dyslexia (DD), and KIAA0319 and ROBO1 appear as more than plausible candidate susceptibility genes for this developmental disorder. Converging evidence indicates that developmental difficulties in oral language and mathematics can predate or co-occur with DD, and substantial genetic correlations have been found between these abilities and reading traits. In this study, we explored the role of eight single-nucleotide polymorphisms spanning within KIAA0319 and ROBO1 genes, and DD as a dichotomic trait, related neuropsychological phenotypes and comorbid language and mathematical (dis)abilities in a large cohort of 493 Italian nuclear families ascertained through a proband with a diagnosis of DD. Marker-trait association was analyzed by implementing a general test of family-based association for quantitative traits (that is, the Quantitative Transmission Disequilibrium Test, version 2.5.1). By providing evidence for significant association with mathematics skills, our data add further result in support of ROBO1 contributing to the deficits in DD and its correlated phenotypes. Taken together, our findings shed further light into the etiologic basis and the phenotypic complexity of this developmental disorder.
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Cognição , Dislexia/genética , Idioma , Proteínas do Tecido Nervoso/genética , Leitura , Receptores Imunológicos/genética , Adolescente , Criança , Estudos de Coortes , Dislexia/psicologia , Estudos de Associação Genética , Pleiotropia Genética , Humanos , Desenvolvimento da Linguagem , Conceitos Matemáticos , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas RoundaboutRESUMO
Descriptions of genes that are adaptively evolving in humans and that carry polymorphisms with an effect on cognitive performances have been virtually absent. SNAP25 encodes a presynaptic protein with a role in regulation of neurotransmitter release. We analysed the intra-specific diversity along SNAP25 and identified a region in intron 1 that shows signatures of balancing selection in humans. The estimated TMRCA (time to the most recent common ancestor) of the SNAP25 haplotype phylogeny amounted to 2.08 million years. The balancing selection signature is not secondary to demographic events or to biased gene conversion, and encompasses rs363039. This SNP has previously been associated to cognitive performances with contrasting results in different populations. We analysed this variant in two Italian cohorts in different age ranges and observed a significant genotype effect for rs363039 on verbal performances in females alone. Post hoc analysis revealed that the effect is driven by differences between heterozygotes and both homozygous genotypes. Thus, heterozygote females for rs363039 display higher verbal performances compared to both homozygotes. This finding was replicated in a cohort of Italian subjects suffering from neuromuscular diseases that do not affect cognition. Heterozygote advantage is one of the possible reasons underlying the maintenance of genetic diversity in natural populations. The observation that heterozygotes for rs363039 display higher verbal abilities compared to homozygotes perfectly fits the underlying balancing selection model. Although caution should be used in inferring selective pressures from observed signatures, SNAP25 might represent the first description of an adaptively evolving gene with a role in cognition.
Assuntos
Inteligência/genética , Seleção Genética , Proteína 25 Associada a Sinaptossoma/genética , Mulheres/psicologia , Criança , Pré-Escolar , Cognição , Estudos de Coortes , Evolução Molecular , Feminino , Genética Populacional , Genótipo , Humanos , Itália , Masculino , Polimorfismo de Nucleotídeo Único , VocabulárioRESUMO
AIM: Obese patients generally are not considered good candidates for wall defect repair, because of associated comorbidities, increased surgical risk, and high risk of surgical site infection and recurrence. The purpose of this retrospective study was to evaluate the results of laparoscopic incisional hernia repair in a group of patients with Body Mass Index (BMI)>35 kg/m2. MATERIAL AND METHOD: From January 2016 to October 2018, 15 obese patients, including 11 females (73.3%) with a BMI > 35 kg/m2 underwent laparoscopic repair of an incisional abdominal hernia. Median BMI was 40 (SD±5). No selection related to comorbidities was performed. As primary endpoints, main postoperative general complications and hernia recurrence were taken into account. Secondary endpoints were the incidence of seroma, hematoma, wound infection and length of hospitalization. In addition, a systematic review of the literature on open and laparoscopic repair techniques was carried out. RESULTS: All patients were treated by laparoscopy and no conversions were required. No intraoperative complications were observed, and no patients underwent early re-intervention. Mortality was zero. One patient (6.6%) presented a seroma, conservatively managed, and evaluated over time without the need of re-intervention. One patient (6.6%) suffered a recurrence a year later, also treated by laparoscopy. Average hospital stay was 2.79 days (DS±0.77). CONCLUSIONS: Despite positive data and good results, laparoscopic treatment of wall defects has yet to be standardized. The feasibility of the laparoscopy for ventral hernias in patients with BMI>35 kg/m2 should be considered. The proposed technique is standardizable and easily reproducible. In terms of complications in the short term (perforations, kidney and pulmonary failure, cardiovascular events) and in the long term (relapses, wound infections, seromas) our results justify recommendation of the minimally invasive approach for almost all patients with abdominal wall defects. KEY WORDS: Laparoscopy, Obese, Ventral hernia.
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Hérnia Ventral , Hérnia Incisional , Laparoscopia , Feminino , Humanos , Estudos Retrospectivos , Seroma/etiologia , Hérnia Ventral/cirurgia , Hérnia Incisional/cirurgia , Laparoscopia/métodos , Obesidade/complicações , Obesidade/cirurgia , Herniorrafia/métodos , Recidiva , Telas Cirúrgicas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
Importance: Understanding the longitudinal, bidirectional associations between disturbed sleep and depression in childhood and adolescence is crucial for the development of prevention and intervention programs. Objective: To test for bidirectional associations and cascade processes between disturbed sleep and depressive symptoms covering both childhood and adolescence and to test for the moderating processes of sex and pubertal status in adolescence. Design, Setting, and Participants: A prospective cohort study using the Québec Longitudinal Study of Child Development (QLSCD; 1997-ongoing). QLSCD's objective is to identify early childhood factors associated with long-term psychosocial and academic adjustment. Data were collected across 8 waves between ages 5 years (2003) and 17 years (2015). Associations were tested through cross-lagged models in childhood (5, 7, and 8 years), and in adolescence (10, 12, 13, 15, and 17 years). Data were analyzed from February to October 2021. Main Outcomes and Measures: Primary outcomes were disturbed sleep and depressive symptoms. Disturbed sleep was parent-reported and included sleep duration, time awake in bed, daytime sleepiness, sleep talking, sleepwalking, night terrors, and nightmares. Depressive symptoms were parent-reported in childhood (Child Behavior Checklist and Revised Ontario Child Health Study Scales), and self-reported in adolescence (Mental Health and Social Inadaptation Assessment for Adolescents). Results: Data on 1689 children (852 female [50.4%]) and 1113 adolescents (595 female [53.5%]) were included in the analyses. In childhood, significant bidirectional associations between depressive symptoms and disturbed sleep at all time points were found, indicating cascade processes (range ß = 0.07; 95% CI, 0.02-012 to ß = 0.15; 95% CI, 0.10-0.19). In adolescence, significant bidirectional associations from depressive symptoms to disturbed sleep (ß = 0.09; 95% CI, 0.04-0.14) and vice versa (ß = 0.10; 95% CI, 0.04-0.16) between 10 and 12 years were found. Between 12 and 13 years, depressive symptoms were modestly associated with disturbed sleep (ß = 0.05; 95% CI, 0.001-0.10) but the reverse association was not significant. Cross-lagged estimates were nonsignificant after 13 years. The associations did not vary as a function of either sex or puberty-by-sex. Conclusions and Relevance: These findings suggest that disturbed sleep is associated with the consolidation of depressive symptoms starting in childhood, which, in turn, is associated with ongoing sleep problems. It is possible that timely and appropriate interventions for incipient disturbed sleep and depression prevent spiraling effects on both domains.
Assuntos
Depressão , Sono , Adolescente , Criança , Pré-Escolar , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Estudos Longitudinais , Saúde Mental , Estudos ProspectivosRESUMO
Converging evidence indicates that developmental problems in oral language and mathematics can predate or co-occur with developmental dyslexia (DD). Substantial genetic correlations have been found between language, mathematics and reading traits, independent of the method of sampling. We tested for association of variants of two DD susceptibility genes, DCDC2 and DYX1C1, in nuclear families ascertained through a proband with DD using concurrent measurements of language and mathematics in both probands and siblings by the Quantitative Transmission Disequilibrium Test. Evidence for significant associations was found between DCDC2 and 'Numerical Facts' (p value = 0.02, with 85 informative families, genetic effect = 0.57) and between 'Mental Calculation' and DYX1C1 markers -3GA (p value = 0.05, with 40 informative families, genetic effect = -0.67) and 1249GT (p value = 0.02, with 49 informative families, genetic effect = -0.65). No statistically significant associations were found between DCDC2 or DYX1C1 and language phenotypes. Both DCDC2 and DYX1C1 DD susceptibility genes appear to have a pleiotropic role on mathematics but not language phenotypes.
Assuntos
Pleiotropia Genética/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Transtornos do Desenvolvimento da Linguagem/genética , Deficiências da Aprendizagem/genética , Matemática , Núcleo Familiar , Criança , Pré-Escolar , Estudos de Coortes , Dislexia/diagnóstico , Dislexia/genética , Feminino , Marcadores Genéticos/genética , Genótipo , Humanos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Deficiências da Aprendizagem/diagnóstico , Desequilíbrio de Ligação , Masculino , Testes Neuropsicológicos , FenótipoRESUMO
Developmental dyslexia (DD) is a complex neurodevelopmental disorder and the most common learning disability among both school-aged children and across languages. Recently, sensory and cognitive mechanisms have been reported to be potential endophenotypes (EPs) for DD, and nine DD-candidate genes have been identified. Animal models have been used to investigate the etiopathological pathways that underlie the development of complex traits, as they enable the effects of genetic and/or environmental manipulations to be evaluated. Animal research designs have also been linked to cutting-edge clinical research questions by capitalizing on the use of EPs. For the present scoping review, we reviewed previous studies of murine models investigating the effects of DD-candidate genes. Moreover, we highlighted the use of animal models as an innovative way to unravel new insights behind the pathophysiology of reading (dis)ability and to assess cutting-edge preclinical models.
Assuntos
Dislexia , Animais , Dislexia/genética , Endofenótipos , Camundongos , Modelos Animais , Herança Multifatorial , LeituraRESUMO
Reading ability is a complex task requiring the integration of multiple cognitive and perceptual systems supporting language, visual and orthographic processes, working memory, attention, motor movements, and higher-level comprehension and cognition. Estimates of genetic and environmental influences for some of these reading-related neurocognitive components vary across reports. By using a multi-level meta-analysis approach, we synthesized the results of behavioral genetic research on reading-related neurocognitive components (i.e. general reading, letter-word knowledge, phonological decoding, reading comprehension, spelling, phonological awareness, rapid automatized naming, and language) of 49 twin studies spanning 4.1-18.5 years of age, with a total sample size of more than 38,000 individuals. Except for language for which shared environment seems to play a more important role, the causal architecture across most of the reading-related neurocognitive components can be represented by the following equation a² > e² > c². Moderators analysis revealed that sex and spoken language did not affect the heritability of any reading-related skills; school grade levels moderated the heritability of general reading, reading comprehension and phonological awareness.
Assuntos
Compreensão , Leitura , Cognição , Humanos , Idioma , LinguísticaRESUMO
Increasing evidence supports the presence of deficits in the visual magnocellular (M) system in developmental dyslexia (DD). The M system is related to the fronto-parietal attentional network. Previous neuroimaging studies have revealed reduced/absent activation within the visual M pathway in DD, but they have failed to characterize the extensive brain network activated by M stimuli. We performed a multivariate pattern analysis on a Region of Interest (ROI) level to differentiate between children with DD and age-matched typical readers (TRs) by combining full-field sinusoidal gratings, controlled for spatial and temporal frequencies and luminance contrast, and a coherent motion (CM) sensitivity task at 6%-CML6, 15%-CML15 and 40%-CML40. ROIs spanning the entire visual dorsal stream and ventral attention network (VAN) had higher discriminative weights and showed higher act1ivation in TRs than in children with DD. Of the two tasks, CM had the greatest weight when classifying TRs and children with DD in most of the ROIs spanning these streams. For the CML6, activation within the right superior parietal cortex positively correlated with reading skills. Our approach highlighted the dorsal stream and the VAN as highly discriminative areas between children with DD and TRs and allowed for a better characterization of the "dorsal stream vulnerability" underlying DD.