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AIM: To determine the feasibility of semi-quantitative haemodynamic parameters derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to assess liver fibrosis. MATERIALS AND METHODS: Seventy-five patients with Child's A classification (males/females=24/51; average age, 58 years; range, 30-80 years) received DCE-MRI 3 days prior to hepatectomy. Semi-quantitative haemodynamic parameters, including the wash-in slope, wash-out slope, and time-to-peak, were calculated from DCE-MRI data. Liver fibrosis of the resected non-tumour liver was graded pathologically from F0 (no fibrosis) to F6 (cirrhosis) in the regions corresponding to those assessed by DCE-MRI. RESULTS: The wash-out slope showed higher interobserver and intra-observer reliabilities than the wash-in slope and time-to-peak. There was a significant positive correlation between the wash-out slope and pathological grade of fibrosis (Spearman's correlation coefficient: r=0.5331, p<0.0001). The area under the receiver operating characteristic curve was 0.8066 when using the wash-out slope to differentiate cirrhosis (grade F6) from non-cirrhosis (grades F0-5). Using the cut-off point that maximised specificity, the sensitivity was 62.07%, specificity was 91.30%, positive predictive value was 81.81%, negative predictive value was 79.25%, and accuracy was 80%. CONCLUSIONS: The wash-out slope derived from DCE-MRI might be potentially useful in assessing liver cirrhosis in patients with Child's A classification before hepatectomy.
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Hepatectomía , Cirrosis Hepática/patología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Medios de Contraste , Estudios de Factibilidad , Femenino , Humanos , Cirrosis Hepática/cirugía , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Cuidados Preoperatorios/métodosRESUMEN
The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H2 ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second.
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BACKGROUND: The dopamine transporter gene (DAT1) and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether a DAT1 haplotype affected functional and structural brain alterations in children with ADHD and whether those alterations were associated with visual memory. METHOD: We recruited a total of 37 drug-naïve children with ADHD (17 with the DAT1 rs27048 (C)/rs429699 (T) haplotype and 20 without the CT haplotype) and 37 typically developing children (17 with the CT haplotype and 20 without the CT haplotype). Visual memory was assessed by the pattern recognition memory (PRM) and spatial recognition memory (SRM) tasks. We analyzed functional and structural brain architecture with regional homogeneity (ReHo) and gray matter volume (GMV). RESULTS: The CT haplotype was associated with decreased ReHo in the left superior occipital gyrus, cuneus, and precuneus; and decreased GMV in the left superior occipital gyrus, cuneus, and precuneus, and in the right angular gyrus. Significant interactions of ADHD and the CT haplotype were found in the right postcentral gyrus for ReHo and in the right supplementary motor area for GMV. For the ADHD-CT group, we found negative correlations of total correct responses in PRM and SRM and positive correlations of mean latency of correct responses in PRM with the GMV in the left superior occipital gyrus, cuneus, and precuneus. CONCLUSIONS: Our findings suggest that the DAT1-related GMV alterations in the posterior cortical regions may contribute to visual memory performance in children with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Corteza Cerebral , Disfunción Cognitiva , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Sustancia Gris/patología , Reconocimiento Visual de Modelos/fisiología , Reconocimiento en Psicología/fisiología , Memoria Espacial/fisiología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/patología , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Niño , Disfunción Cognitiva/etiología , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Femenino , Neuroimagen Funcional , Sustancia Gris/diagnóstico por imagen , Haplotipos , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Benefit from chemotherapy for well-differentiated/de-differentiated (WD/DD) liposarcomas has been reported to be minimal, however traditional response criteria may not adequately capture positive treatment effect. In this study, we evaluate benefit from first-line chemotherapy and characterize imaging response characteristics in patients with retroperitoneal (RP) WD/DD liposarcoma treated at The University of Texas MD Anderson Cancer Center. Response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) and an exploratory analysis of vascular response was characterized. Among 82 patients evaluable for response to first-line therapy, 31 patients received neoadjuvant chemotherapy for localized/locally advanced disease; 51 received chemotherapy for unresectable recurrent/metastatic disease. Median overall survival from the start of chemotherapy was 29 months (95% CI 24-40 months). Response rates by RECIST: partial response (PR) 21% (17/82), stable disease (SD) 40%, and progression (PD) 39%. All RECIST responses were in patients receiving combination chemotherapy. A qualitative vascular response was seen in 24 patients (31%). Combination chemotherapy yields a response rate of 24% and a clinical benefit rate (CR/PR/SD > 6 months) of 44%, higher than previously reported in DD liposarcoma. A higher percentage of patients experience a vascular response with chemotherapy that is not adequately captured by RECIST in these large heterogeneous tumors.
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Liposarcoma , Terapia Neoadyuvante , Neoplasias Retroperitoneales , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Liposarcoma/mortalidad , Liposarcoma/patología , Liposarcoma/terapia , Masculino , Persona de Mediana Edad , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND AND PURPOSE: Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. MATERIALS AND METHODS: Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. RESULTS: Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized ß = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized ß = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity (F2,12 = 0.284, P = .757, R2 = 0.045). CONCLUSIONS: In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis.
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Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Hipocampo/patología , Adulto , Atrofia , Mapeo Encefálico , Imagen de Difusión por Resonancia Magnética , Epilepsia del Lóbulo Temporal/patología , Femenino , Lateralidad Funcional , Giro del Cíngulo/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , EsclerosisRESUMEN
BACKGROUND: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males. METHOD: The 94 participants (aged 9-19 years) - 20 male youth with ASD, 20 unaffected brothers and 54 TD males - received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference. RESULTS: We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers. CONCLUSIONS: Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.
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Trastorno del Espectro Autista , Corteza Cerebral/fisiopatología , Conectoma/métodos , Endofenotipos , Sustancia Gris/patología , Hermanos , Sustancia Blanca/patología , Adolescente , Adulto , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Niño , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Methylphenidate and atomoxetine are commonly prescribed for treating attention deficit hyperactivity disorder (ADHD). However, their therapeutic neural mechanisms remain unclear. METHOD: After baseline evaluation including cognitive testing of the Cambridge Neuropsychological Test Automated Battery (CANTAB), drug-naive children with ADHD (n = 46), aged 7-17 years, were randomly assigned to a 12-week treatment with methylphenidate (n = 22) or atomoxetine (n = 24). Intrinsic brain activity, including the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo), was quantified via resting-state functional magnetic resonance imaging at baseline and week 12. RESULTS: Reductions in inattentive symptoms were related to increased fALFF in the left superior temporal gyrus and left inferior parietal lobule for ADHD children treated with methylphenidate, and in the left lingual gyrus and left inferior occipital gyrus for ADHD children treated with atomoxetine. Hyperactivity/impulsivity symptom reductions were differentially related to increased fALFF in the methylphenidate group and to decreased fALFF in the atomoxetine group in bilateral precentral and postcentral gyri. Prediction analyses in the atomoxetine group revealed negative correlations between pre-treatment CANTAB simple reaction time and fALFF change in the left lingual gyrus and left inferior occipital gyrus, and positive correlations between pre-treatment CANTAB simple movement time and fALFF change in bilateral precentral and postcentral gyri and left precuneus, with a negative correlation between movement time and the fALFF change in the left lingual gyrus and the inferior occipital gyrus. CONCLUSIONS: Our findings suggest differential neurophysiological mechanisms for the treatment effects of methylphenidate and atomoxetine in children with ADHD.
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Inhibidores de Captación Adrenérgica/uso terapéutico , Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Encéfalo/fisiopatología , Inhibidores de Captación de Dopamina/uso terapéutico , Metilfenidato/uso terapéutico , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Encéfalo/diagnóstico por imagen , Niño , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Corteza Somatosensorial/diagnóstico por imagen , Corteza Somatosensorial/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: The relationship between white-matter tracts and executive functions (EF) in attention deficit hyperactivity disorder (ADHD) has not been well studied and previous studies mainly focused on frontostriatal (FS) tracts. The authors explored the microstructural property of several fibre tracts hypothesized to be involved in EF, to correlate their microstructural property with EF, and to explore whether such associations differ between ADHD and typically developing (TD) youths. METHOD: We assessed 45 youths with ADHD and 45 individually matched TD youths with a computerized test battery for multiple dimensions of EF. From magnetic resonance imaging, FS tract, superior longitudinal fasciculus (SLF), arcuate fasciculus (AF) and cingulum bundle (CB) were reconstructed by diffusion spectrum imaging tractography. The generalized fractional anisotropy (GFA) values of white-matter tracts were computed to present microstructural property of each tract. RESULTS: We found lower GFA in the left FS tract, left SLF, left AF and right CB, and poorer performance in set-shifting, sustained attention, cognitive inhibition and visuospatial planning in ADHD than TD. The ADHD and TD groups demonstrated different association patterns between EF and fibre tract microstructural property. Most of the EF were associated with microstructural integrity of the FS tract and CB in TD youths, while with that of the FS tract, SLF and AF in youths with ADHD. CONCLUSIONS: Our findings support that the SLF, AF and CB also involve in a wide range of EF and that the main fibre tracts involved in EF are different in youths with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Atención , Función Ejecutiva , Red Nerviosa/fisiopatología , Vías Nerviosas/fisiopatología , Sustancia Blanca/fisiopatología , Adolescente , Anisotropía , Estudios de Casos y Controles , Niño , Imagen de Difusión Tensora , Femenino , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , TaiwánRESUMEN
Neurological decompression sickness (DCS) is a rare condition that commonly leads to spinal cord injury. We report the case of a 30-year-old man who developed left-sided weakness and numbness after diving to a maximum depth of 15 m with a total dive time of 205min (10 repetitive dives). To the best of our knowledge, only six cases diagnosed as Brown-Séquard syndrome caused by DCS have been reported in the literature. Divers should be aware of the risk factors of DCS before diving and clinicians should make the diagnosis of spinal cord DCS based primarily on clinical symptoms, not on magnetic resonance imaging findings.
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Síndrome de Brown-Séquard/diagnóstico , Industria de la Construcción , Enfermedad de Descompresión/diagnóstico , Buceo/efectos adversos , Oxigenoterapia Hiperbárica/métodos , Enfermedades Profesionales/diagnóstico , Exposición Profesional/efectos adversos , Adulto , Síndrome de Brown-Séquard/etiología , Síndrome de Brown-Séquard/fisiopatología , Síndrome de Brown-Séquard/terapia , Enfermedad de Descompresión/complicaciones , Enfermedad de Descompresión/fisiopatología , Enfermedad de Descompresión/terapia , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades Profesionales/fisiopatología , Enfermedades Profesionales/terapia , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Atopic dermatitis affects 15-30% of children worldwide. Onset of disease usually occurs within the first year of life, over half of which regress by 6 years of age. The aim of this study was to investigate the risk factors related to the persistence of infantile atopic dermatitis. METHODS: In this birth cohort study, patients were enrolled prenatally and followed until 6 years of age; 246 patients had infantile atopic dermatitis at 6 months of age. Family history, maternal and paternal total and specific Immunoglobulin E (IgE) levels, and cord blood IgE were recorded. Clinical examination, questionnaire survey, and blood samples for total and specific IgE of the children were collected at each follow-up visit. RESULTS: Of the 246 patients with infantile atopic dermatitis at 6 months of age, 48 patients had persisted atopic dermatitis at 6 years of age (19.5%). Risk factors associated with persistent infantile atopic dermatitis included egg white sensitization (odds ratio: 3.801, P = 0.020), and atopic dermatitis involving two or more areas at 6 months old (odds ratio: 2.921, P = 0.018) after multivariate analysis with logistic regression. Patients with persistent infantile atopic dermatitis had a higher risk of asthma before 6 years old (39.6% vs 24.2%, P = 0.032). CONCLUSION: Egg white sensitization and the initial involvement of two or more areas at 6 months of age were associated with the persistent infantile atopic dermatitis. Patients with persistent infantile atopic dermatitis are more likely to develop asthma by 6 years of age.
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Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Lactante , Recién Nacido , Masculino , Exposición Materna , Embarazo , Estudios Prospectivos , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
OBJECTIVES: To investigate effects of platelet-rich plasma on tendon cell proliferation and the underlying molecular mechanisms. MATERIALS AND METHODS: Platelet-rich plasma was prepared manually by two-step centrifugation. Proliferation was evaluated in cultured rat tendon cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell cycle progression was assessed by flow cytometry. Messenger RNA expression of proliferating cell nuclear antigen (PCNA), cyclin E1, A2 and B1, and cyclin-dependent kinases (Cdks) 1 and 2 was assessed by real-time polymerase chain reaction. Protein expression of the above cyclins and Cdks and of signal transducer and activator of transcription (Stat) 3 and p27 was evaluated by western blotting. RESULTS: Platelet-rich plasma used in the present study had concentrations of platelets, TGF-ß1 and PDGF over 3-fold higher than normal whole blood. Platelet-rich plasma enhanced tendon cell proliferation (P = 0.008) by promoting G1 /S phase transition in the cell cycle, and increased expression of PCNA, cyclin E1, A2 and B1, Cdks1 and 2, and phosphorylated Stat3, while inhibiting p27 expression. CONCLUSIONS: Platelet-rich plasma contains high concentrations of TGF-ß1 and PDGF that increase tendon cell proliferation by modulating Stat3/p27(Kip1), which enhances expression of cyclin-Cdk complexes that promote cell cycle progression. These results provide molecular evidence for positive effects of platelet-rich plasma on tendon cell proliferation, which can be useful in clinical applications of tendon injury.
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Proliferación Celular , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Quinasas Ciclina-Dependientes/genética , Ciclinas/genética , Plasma Rico en Plaquetas/metabolismo , Factor de Transcripción STAT3/metabolismo , Tendones/citología , Animales , Proteína Quinasa CDC2 , Quinasa 2 Dependiente de la Ciclina/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , ARN Mensajero/genética , Ratas , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease. METHODS: Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-ß, and mRNA expression levels of RORγt and Foxp3 were tested. RESULTS: Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A. CONCLUSION: Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.
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Citocinas/sangre , Citocinas/genética , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/genética , ARN Mensajero/genética , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Recuento de Linfocito CD4 , Preescolar , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Regulación de la Expresión Génica , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunofenotipificación , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunologíaRESUMEN
BACKGROUND: Deficits in executive function (EF), impaired school functioning and altered white matter integrity in frontostriatal networks have been associated with attention-deficit/hyperactivity disorder (ADHD). However, relationships between impairments in these areas are unclear. Using a sample of youths with and without ADHD, this study examined the association between microstructural integrity of frontostriatal tracts and school dysfunction and the mediating roles of EF and ADHD symptoms in this association. METHOD: The sample included 32 Taiwanese youths with ADHD and 32 age-, sex-, handedness- and IQ-matched typically-developing (TD) youths. Participants were assessed using psychiatric interviews, parent reports on ADHD symptoms and school functioning, and EF measures from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The frontostriatal tracts were reconstructed by diffusion spectrum imaging (DSI) tractography and were subdivided into four functionally distinct segments: caudate-dorsolateral, caudate-medial prefrontal, caudate-orbitofrontal and caudate-ventrolateral tracts. RESULTS: Youths with ADHD, relative to TD youths, showed altered white matter integrity in all four bilateral pairs of frontostriatal tracts (decreased general fractional anisotropy, GFA), had poor attention, vigilance and response inhibition, and showed impaired school functioning. Altered microstructural integrity in frontostriatal tracts was significantly associated with school dysfunction, which was mediated by EF measures of attention/vigilance and response inhibition in addition to inattention and hyperactivity symptoms. CONCLUSIONS: Our findings demonstrate an association between white matter integrity in the frontostriatal networks and school functioning and suggest that EF deficits and ADHD symptoms may be the mediating mechanisms for this association. Future research is needed to test the directionality and specificity of this finding.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Función Ejecutiva , Sustancia Blanca/fisiopatología , Adolescente , Estudios de Casos y Controles , Niño , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Instituciones Académicas , TaiwánRESUMEN
Face memory deficits may be a bipolar disorder (BD) endophenotype. BD (n=27) and unaffected youth at risk (n=13) exhibited middle frontal gyrus hypoactivation during successful vs. unsuccessful encoding. Parahippocampal gyrus dysfunction was found in BD and at-risk youth (vs. low-risk, n=37). Middle occipital gyrus hypoactivation was only present in BD.
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Trastorno Bipolar/fisiopatología , Trastorno Bipolar/psicología , Encéfalo/fisiopatología , Emociones , Expresión Facial , Imagen por Resonancia Magnética , Adolescente , Endofenotipos , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Masculino , Memoria , Lóbulo Occipital/fisiopatología , Giro Parahipocampal/fisiopatología , RiesgoRESUMEN
BACKGROUND: Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That Reelin interacts with the coagulation components and elicits a functional role in hemostasis has not yet been elucidated. OBJECTIVES: The hemostatic activity of Reelin is investigated and defined in this study. METHODS: The interplay of Reelin with coagulation components was elucidated by far-Western and liposome/platelet binding assays. In vivo and ex vivo hemostasis-related analyses of Reelin-deficient mice and plasma were also performed. RESULTS: Reelin interacted with the liposomes containing phosphatidylserine (PS) or phosphatidylcholine. Instead of interacting with known Reelin receptors (ApoE receptor 2, very low density lipoprotein receptor and integrin ß1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FXa was also demonstrated with the Kd of 11.7 and 21.2 nm, respectively. Reelin-deficient mice displayed a prolonged bleeding time and an increase in rebleeding rate. Despite the fact that Reelin deficiency had no significant effect on the clotting time of prothrombin and activated partial thromboplastin time, the fibrin clot formation was abnormal and the fibrin clot structure was relatively loosened with reduced clot strength. Abnormal fibrinogen expression did not account for the hemostatic defects associated with Reelin deficiency. Instead, thrombin generation was impaired concomitant with an altered prothrombin cleavage pattern. CONCLUSIONS: By interacting with platelet phospholipids and the coagulation factors, thrombin and FXa, Reelin plays a selective role in coagulation activation, leading to thrombin generation and formation of a normal fibrin clot.
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Moléculas de Adhesión Celular Neuronal/sangre , Moléculas de Adhesión Celular Neuronal/genética , Proteínas de la Matriz Extracelular/sangre , Proteínas de la Matriz Extracelular/genética , Hemostasis , Proteínas del Tejido Nervioso/sangre , Proteínas del Tejido Nervioso/genética , Serina Endopeptidasas/sangre , Serina Endopeptidasas/genética , Trombina/biosíntesis , Animales , Anexina A5/química , Coagulación Sanguínea , Factores de Coagulación Sanguínea/química , Plaquetas/citología , Factor Xa/química , Fibrina/química , Fibrinógeno/química , Genotipo , Glicoproteínas/química , Lípidos/química , Liposomas/química , Ratones , Ratones Transgénicos , Tiempo de Tromboplastina Parcial , Fosfatidilcolinas/química , Fosfatidilserinas/química , Activación Plaquetaria , Agregación Plaquetaria , Unión Proteica , Tiempo de Protrombina , Proteína Reelina , Trombina/químicaRESUMEN
BACKGROUND: Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age. METHOD: During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing. RESULTS: Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces. CONCLUSIONS: Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.
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Amígdala del Cerebelo/fisiopatología , Atención/fisiología , Trastorno Bipolar/fisiopatología , Expresión Facial , Giro del Cíngulo/fisiopatología , Corteza Prefrontal/fisiopatología , Putamen/fisiopatología , Adolescente , Adulto , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Increased intra-individual variability (IIV) in reaction time (RT) across various tasks is one ubiquitous neuropsychological finding in attention deficit hyperactivity disorder (ADHD). However, neurobiological underpinnings of IIV in individuals with ADHD have not yet been fully delineated. The ex-Gaussian distribution has been proved to capture IIV in RT. The authors explored the three parameters [µ (mu), σ (sigma), τ (tau)] of an ex-Gaussian RT distribution derived from the Conners' continuous performance test (CCPT) and their correlations with the microstructural integrity of the frontostriatal-caudate tracts and the cingulum bundles. METHOD: We assessed 28 youths with ADHD (8-17 years; 25 males) and 28 age-, sex-, IQ- and handedness-matched typically developing (TD) youths using the CCPT, Wechsler Intelligence Scale for Children, 3rd edition and magnetic resonance imaging (MRI). Microstructural integrity, indexed by generalized fractional anisotropy (GFA), was measured by diffusion spectrum imaging tractrography on a 3-T MRI system. RESULTS: Youths with ADHD had larger σ (s.d. of Gaussian distribution) and τ (mean of exponential distribution) and reduced GFA in four bilateral frontostriatal tracts. With increased inter-stimulus intervals of CCPT, the magnitude of greater τ in ADHD than TD increased. In ADHD youths, the cingulum bundles and frontostriatal integrity were associated with three ex-Gaussian parameters and with µ (mean of Gaussian distribution) and τ, respectively; while only frontostriatal GFA was associated with µ and τ in TD youths. CONCLUSIONS: Our findings suggest the crucial role of the integrity of the cingulum bundles in accounting for IIV in ADHD. Involvement of different brain systems in mediating IIV may relate to a distinctive pathophysiological processing and/or adaptive compensatory mechanism.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Giro del Cíngulo/fisiopatología , Desempeño Psicomotor/fisiología , Sustancia Blanca/fisiopatología , Adolescente , Estudios de Casos y Controles , Niño , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Distribución Normal , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is recognized as an early-onset neuropsychiatric disorder with executive dysfunctions and neurobiological deficits. The authors compared executive functions and microstructural integrity of the frontostriatal circuit in children with ADHD and typically developing children. Method We assessed 25 children with ADHD and 25 age-, sex-, handedness- and intelligence-matched typically developing children by using psychiatric interviews, the Wechsler Intelligence Scale for Children - third edition, and the tasks involving executive functions in the Cambridge Neuropsychological Test Automated Battery. The frontostriatal tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into four functionally distinct segments, including dorsolateral, medial prefrontal, orbitofrontal and ventrolateral tracts. Tract-specific and matched case-control analyses were used and generalized fractional anisotropy values were computed. RESULTS: Children with ADHD had lower generalized fractional anisotropy of all the bilateral frontostriatal fiber tracts and poorer performance in verbal and spatial working memory, set-shifting, sustained attention, cognitive inhibition and visuospatial planning. The symptom severity of ADHD and the executive functioning performance significantly correlated with integrity of the frontostriatal tracts, particularly the left orbitofrontal and ventrolateral tracts. Children with ADHD also demonstrated loss of the leftward asymmetry in the dorsolateral and medial prefrontal tracts that was present in typically developing children. CONCLUSIONS: Our findings demonstrate disturbed structural connectivity of the frontostriatal circuitry in children with ADHD and add new evidence of associations between integrity of the frontostriatal tracts and measures of core symptoms of ADHD and a wide range of executive dysfunctions in both groups.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Ganglios Basales/fisiopatología , Función Ejecutiva/fisiología , Pruebas Neuropsicológicas , Corteza Prefrontal/fisiopatología , Anisotropía , Trastorno por Déficit de Atención con Hiperactividad/patología , Ganglios Basales/patología , Estudios de Casos y Controles , Niño , Imagen de Difusión Tensora , Humanos , Interpretación de Imagen Asistida por Computador , Modelos Lineales , Análisis Multinivel , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Corteza Prefrontal/patología , Índice de Severidad de la Enfermedad , Escalas de WechslerRESUMEN
BACKGROUND AND PURPOSE: ARHSP-TCC is characterized by progressive leg spasticity, ataxia, and cognitive dysfunction. Although mutations in the human SPG11 gene were identified as responsible for ARHSP-TCC, the cerebral fiber integrity has not been assessed systemically. The objective of this study was to assess cerebral fiber integrity and its clinical significance in patients with ARHSP-TCC. MATERIALS AND METHODS: Five patients from 2 families who were clinically and genetically confirmed to have ARHSP-TCC were examined by neuropsychological evaluation and DSI of the brain. We performed voxel-based GFA analysis for global white matter evaluation, tractography-based analysis for tract-to-tract comparisons, and tract-specific analysis of the CST to evaluate microstructural integrity along the axonal direction. RESULTS: The neuropsychological evaluation revealed widespread cognitive decline across all domains. Voxel-based analysis showed global reduction of GFA in the cerebral white matter. Tractography-based analysis revealed a significant reduction of the microstructural integrity in all neural fiber types, while commissure and association fibers had more GFA reduction than projection fibers (P < .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P < .00001, P = .018). Tract-specific analysis of the CST validated a "dying-back" phenomenon (R(2) = 0.68, P < .00001). CONCLUSIONS: There was a characteristic gradation in the reduction of microstructural integrity among fiber types and within the CC in patients with the SPG11 mutation. The dying-back process in CST might explain the pathogenic mechanisms for ARHSP-TCC.