Cerebellar and brainstem differences in children with developmental coordination disorder: A voxel-based morphometry study

Developmental coordination disorder (DCD) is a neurodevelopmental disorder that significantly impairs a child’s ability to learn motor skills and to perform everyday activities. The cause of DCD is unknown; however, evidence suggests that children with DCD have altered brain structure and function. While the cerebellum has been hypothesised to be involved in developmental coordination disorder, no studies have specifically examined cerebellar structure in this population. The purpose of our study was to examine cerebellar differences in children with DCD compared to typically-developing children. Using voxel-based morphometry, we assessed cerebellar morphology in children 8–12 years of age. Forty-six children (12 typically-developing and 34 with DCD) were investigated using high resolution T1-weighted images, which were then processed using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) toolbox for a region of interest-based examination of the cerebellum. Results revealed that children with DCD had reduced grey matter volume in several regions, namely: the brainstem, right/left crus I, right crus II, left VI, right VIIb, and right VIIIa lobules. Further, Pearson correlations revealed significant positive associations between the total motor percentile score on the Movement Assessment Battery for Children-2 and regions that had reduced grey matter volume in our cohort (brainstem, left crus I, right VIIb, and right VIIIa). These findings indicate that reductions in cerebellar grey matter volume are associated with poorer motor skills. Given the cerebellum’s involvement in internal models of movement, results of this study may help to explain why children with DCD struggle to learn motor skills

Cerebellar Differences after Rehabilitation in Children with Developmental Coordination Disorder

Developmental coordination disorder (DCD) affects a child’s ability to learn motor skills. Cognitive Orientation to daily Occupational Performance (CO-OP) is one of the recommended treatments to help achieve functional motor goals. The purpose of this study was to determine if CO-OP intervention induces functional improvements and structural changes in the cerebellum of children with DCD. Using a randomized waitlist-controlled trial, we investigated the effects of CO-OP intervention on cerebellar volume in 47 children with DCD (8–12 years old). Outcome measures included the Canadian Occupational Performance Measure, Performance Quality Rating Scale (PQRS), and Bruininks–Oseretsky Test of Motor Proficiency-2. The SUIT toolbox was used to carry out voxel-based morphometry using T1-weighted MRI scans. Children with DCD showed improved motor outcomes and increased gray matter volume in the brainstem, right crus II, bilateral lobules VIIIb, and left lobule IX following CO-OP. Significant associations were found between PQRS scores and regional gray matter changes in the brainstem, right crus II, right lobule VIIb, right and left lobule VIIIb, and vermis IX. Given the improved motor and brain outcomes with CO-OP, it is recommended that children with DCD be referred for this rehabilitation intervention

Sirtuin1: a promising serum protein marker for early detection of Alzheimer's disease.

Sirtuin (SIRT) pathway has a crucial role in Alzheimer's disease (AD). The present study evaluated the alterations in serum sirtuin1 (SIRT1) concentration in healthy individuals (young and old) and patients with AD and mild cognitive impairment (MCI). Blood samples were collected from 40 AD and 9 MCI patients as cases and 22 young healthy adults and 22 healthy elderly individuals as controls. Serum SIRT1 was estimated by Surface Plasmon Resonance (SPR), Western Blot and Enzyme Linked Immunosorbent Assay (ELISA). A significant (p<0.0001) decline in SIRT1 concentration was observed in patients with AD (2.27 ± 0.46 ng/µl) and MCI (3.64 ± 0.15 ng/µl) compared to healthy elderly individuals (4.82 ± 0.4 ng/µl). The serum SIRT1 concentration in healthy elderly was also significantly lower (p<0.0001) compared to young healthy controls (8.16 ± 0.87 ng/µl). This study, first of its kind, has demonstrated, decline in serum concentration of SIRT1 in healthy individuals as they age. In patients with AD and MCI the decline was even more pronounced, which provides an opportunity to develop this protein as a predictive marker of AD in early stages with suitable cut off values

A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: Design, synthesis, activity against multidrug-resistant bacteria and Candida

AbstractLactoferrin (LF) is believed to contribute to the host's defense against microbial infections. This work focuses on the antibacterial and antifungal activities of a designed peptide, L10 (WFRKQLKW) by modifying the first eight N-terminal residues of bovine LF by selective homologous substitution of amino acids on the basis of hydrophobicity, L10 has shown potent antibacterial and antifungal properties against clinically isolated extended spectrum beta lactamases (ESBL), producing gram-negative bacteria as well as Candida strains with minimal inhibitory concentrations (MIC) ranging from 1 to 8μg/mL and 6.5μg/mL, respectively. The peptide was found to be least hemolytic at a concentration of 800μg/mL. Interaction with lipopolysaccharide (LPS) and lipid A (LA) suggests that the peptide targets the membrane of gram-negative bacteria. The membrane interactive nature of the peptide, both antibacterial and antifungal, was further confirmed by visual observations employing electron microscopy. Further analyses, by means of propidium iodide based flow cytometry, also supported the membrane permeabilization of Candida cells. The peptide was also found to possess anti-inflammatory properties, by virtue of its ability to inhibit cyclooxygenase-2 (COX-2). L10 therefore emerges as a potential therapeutic remedial solution for infections caused by ESBL positive, gram-negative bacteria and multidrug-resistant (MDR) fungal strains, on account of its multifunctional activities. This study may open up new approach to develop and design novel antimicrobials

Level of serum SIRT1 (ng/µl) in respect to demographic parameters by SPR.

<p>Level of serum SIRT1 (ng/µl) in respect to demographic parameters by SPR.</p

Sensogram showing the immobilization of SIRT1 antibody on CM5 sensor chip.

<p>Sensogram showing the immobilization of SIRT1 antibody on CM5 sensor chip.</p

Estimation of serum SIRT1 using ELISA technology.

<p>(A) Standard curve plotted between known concentration of SIRT1 and absorbance obtained at 450 nm. (B) Bar Diagram showing the difference in serum SIRT1 concentration between different groups (C) Scatter Diagram showing the difference in serum SIRT1 concentration between different groups.</p

Demographic data of patients and controls.

<p>Demographic data of patients and controls.</p

Western blot and density analysis (A) to confirm the presence of SIRT1 in serum of AD patients(lane1,2), MCI patients(lane3,4), Elderly control(5,6) and young control(7,8).

<p>(B) 1,3,9,12,15,18 and 21 µg of pure SIRT1 loaded in lane 1–7 respectively.</p