Influence of Processing Pipeline on Cortical Thickness Measurement

In recent years, replicability of neuroscientific findings, specifically those concerning correlates of morphological properties of gray matter (GM), have been subject of major scrutiny. Use of different processing pipelines and differences in their estimates of the macroscale GM may play an important role in this context. To address this issue, here, we investigated the cortical thickness estimates of three widely used pipelines. Based on analyses in two independent large-scale cohorts, we report high levels of within-pipeline reliability of the absolute cortical thickness-estimates and comparable spatial patterns of cortical thickness-estimates across all pipelines. Within each individual, absolute regional thickness differed between pipelines, indicating that in-vivo thickness measurements are only a proxy of actual thickness of the cortex, which shall only be compared within the same software package and thickness estimation technique. However, at group level, cortical thickness-estimates correlated strongly between pipelines, in most brain regions. The smallest between-pipeline correlations were observed in para-limbic areas and insula. These regions also demonstrated the highest interindividual variability and the lowest reliability of cortical thickness-estimates within each pipeline, suggesting that structural variations within these regions should be interpreted with caution

Vat polymerization 3D printing of composite acrylate photopolymer-based coated glass beads

Vat photopolymerization-based three-dimensional (3D) printing techniques have been used as an efficient method for complex and special geometries in various applications. Composites are also a group of polymer materials that are obtained by adding a reinforcing component such as filler, fibres with different origins. Therefore, the development of 3D printable composites is paramount due to their high precision and speed of production. Glass beads (GBs) have been favorites as economical reinforcement agents for their chemical stability, water resistance in acidic environments, dimensional stability, and eco-friendly properties. In this study, 3D printable composites based on coated glass beads (CGBs) have been prepared. First, the beads are coated with ultraviolet (UV) curable resins to improve the interface with the polymer matrix. Then, CGBs are mixed with 3D printing resin and formulated for digital light processing (DLP) printing. The coating process is checked by scanning electron microscopy (SEM), and the mechanical properties of the 3D-printed composite structures have been evaluated by bending and compression tests. Also, the fracture behavior of cured resin has been checked with SEM. Mechanical property investigations have shown the success of the 3D printing of the CGBs into a photopolymer resin (PR) composite with behavior modification and compatibility of the interface with the matrix in practice

Can prodromal symptoms predict recurrence of vasovagal syncope?

Background: Vasovagal syncope (VVS) is a common symptom with empirical therapy and high recurrence rate. Our goal was to determine whether the pattern of presyncopal prodromal symptoms can predict the recurrence probability of vasovagal syncope. Methods: Seventy-nine consecutive patients (male/female: 53/26) with history of VVS and positive tilt table test (TTT) were enrolled in the study and completed the follow-up time for one year. They all had normal electrocardiograms and cardiac echocardiography without underlying disease. All of them were evaluated meticulously for prodromal symptoms (diaphoresis, nausea, palpitation and blurred vision) and frequency of syncopal spells in their past medical history. They received metoprolol at maximum tolerated dose and were taught tilt training as an empirical therapy after TTT. Results: Fifty-four patients (68.4) reported at least one of the four main prodromal symptoms. Median syncopal ± presyncopal spells were 4 episodes. Forty-two patients (53.2) experienced recurrence of syncope or presyncope during the follow-up period. In recurrent symptomatic patients, diaphoresis had been more significantly reported in their past medical history (p = 0.018) and they had more syncopal spells before TTT (p = 0.001). Age, gender and type of TTT response did not have any effect on the recurrence of VVS. Conclusions: Patients with a history of diaphoresis as a prodromal symptom and more pre-tilt syncopal attacks experience more syncopal or presyncopal spells during follow-up. Copyright © 2008 Via Medica

Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration.

OBJECTIVE: To characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families. METHODS: We used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model. RESULTS: We identified 3 homozygous inactivating variants, including a splice site substitution (c.301+2T>A) causing aberrant transcript processing and accelerated degradation of a resulting protein lacking exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA). We show that loss of SQSTM1 causes impaired production of ubiquitin-positive protein aggregates in response to misfolded protein stress and decelerated autophagic flux. The consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in zebrafish documented a variable but reproducible phenotype characterized by cerebellum anomalies ranging from depletion of axonal connections to complete atrophy. We provide a detailed clinical characterization of the disorder; the natural history is reported for 2 siblings who have been followed up for >20 years. CONCLUSIONS: This study offers an accurate clinical characterization of this recently recognized neurodegenerative disorder caused by biallelic inactivating mutations in SQSTM1 and links this phenotype to defective selective autophagy

Gray Matter Changes in Parkinson's and Alzheimer's Disease and Relation to Cognition

Purpose of Review We summarize structural (s)MRI findings of gray matter (GM) atrophy related to cognitive impairment in Alzheimer's disease (AD) and Parkinson's disease (PD) in light of new analytical approaches and recent longitudinal studies results. Recent Findings The hippocampus-to-cortex ratio seems to be the best sMRI biomarker to discriminate between various AD subtypes, following the spatial distribution of tau pathology, and predict rate of cognitive decline. PD is clinically far more variable than AD, with heterogeneous underlying brain pathology. Novel multivariate approaches have been used to describe patterns of early subcortical and cortical changes that relate to more malignant courses of PD. New emerging analytical approaches that combine structural MRI data with clinical and other biomarker outcomes hold promise for detecting specific GM changes in the early stages of PD and preclinical AD that may predict mild cognitive impairment and dementia conversion

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'

Stretching health manpower : the rural health auxiliary

PhotocopyIDRC supported. Article on the use of the auxiliary health worker in delivering health services, with information on the Kavar Village Health Worker Pilot Project conducted in Iran - examines the effectiveness of auxiliary health workers in terms of reducing mortality and fertility rates. Bibliographic notes