Integration of graph network with kernel SVM and logistic regression for identification of biomarkers in SCA12 and its diagnosis.

Spinocerebellar ataxia type 12 is a hereditary and neurodegenerative illness commonly found in India. However, there is no established noninvasive automatic diagnostic system for its diagnosis and identification of imaging biomarkers. This work proposes a novel four-phase machine learning-based diagnostic framework to find spinocerebellar ataxia type 12 disease-specific atrophic-brain regions and distinguish spinocerebellar ataxia type 12 from healthy using a real structural magnetic resonance imaging dataset. Firstly, each brain region is represented in terms of statistics of coefficients obtained using 3D-discrete wavelet transform. Secondly, a set of relevant regions are selected using a graph network-based method. Thirdly, a kernel support vector machine is used to capture nonlinear relationships among the voxels of a brain region. Finally, the linear relationship among the brain regions is captured to build a decision model to distinguish spinocerebellar ataxia type 12 from healthy by using the regularized logistic regression method. A classification accuracy of 95% and a harmonic mean of precision and recall, i.e. F1-score of 94.92%, is achieved. The proposed framework provides relevant regions responsible for the atrophy. The importance of each region is captured using Shapley Additive exPlanations values. We also performed a statistical analysis to find volumetric changes in spinocerebellar ataxia type 12 group compared to healthy. The promising result of the proposed framework shows that clinicians can use it for early and timely diagnosis of spinocerebellar ataxia type 12.

Folate Receptor Targeting Mn(II) Complex Encapsulated Porous Silica Nanoparticle as an MRI Contrast Agent for Early-State Detection of Cancer.

Cancer is recognized as one of the major causes of mortality, however, early-stage detection can increase the survival chance greatly. It is recognized that folate receptors are gradually overexpressed in the cellular membrane with the progress of cancer from stage 1 to stage 4. Utilizing the fact, herein, developed a porous silica nanoparticle system C1@SiO2-FA-NP; A) impregnated with thermodynamically stable Mn(II) complex (1) molecules within the core of the nanoparticle, and B) surface functionalized with folate units. It exhibited a high longitudinal relaxivity value r1 = 21.45 mM-1s-1 that substantially increased to r1 = 40.97 mM-1s-1 in the presence of 0.67 mM concentration of BSA under the physiological condition. The in vitro fluorescent images after surface conjugation of C1@SiO2-FA-NP with FITC (fluorescein isothiocyanate) buttressed the inclusion of the nanoparticle exclusively within the cancerous HeLa cells than that of healthy HEK293 cells. The importance of the surface-bound folate unit in the nanoparticle is further established by comparing the fluorescent images of HeLa cells in the absence of the group. Finally, the applicability of C1@SiO2-FA-NP as the T1-weighted MRI contrast agent for early-stage cancer diagnosis is established within C57BL/6 mice after infecting the mice with HeLa cells.

Structural and white matter changes associated with duration of Braille education in early and late blind children.

In early (EB) and late blind (LB) children, vision deprivation produces cross-modal plasticity in the visual cortex. The progression of structural- and tract-based spatial statistics changes in the visual cortex in EB and LB, as well as their impact on global cognition, have yet to be investigated. The purpose of this study was to determine the cortical thickness (CT), gyrification index (GI), and white matter (WM) integrity in EB and LB children, as well as their association to the duration of blindness and education. Structural and diffusion tensor imaging data were acquired in a 3T magnetic resonance imaging in EB and LB children (n = 40 each) and 30 sighted controls (SCs) and processed using CAT12 toolbox and FSL software. Two sample t-test was used for group analyses with P < 0.05 (false discovery rate-corrected). Increased CT in visual, sensory-motor, and auditory areas, and GI in bilateral visual cortex was observed in EB children. In LB children, the right visual cortex, anterior-cingulate, sensorimotor, and auditory areas showed increased GI. Structural- and tract-based spatial statistics changes were observed in anterior visual pathway, thalamo-cortical, and corticospinal tracts, and were correlated with education onset and global cognition in EB children. Reduced impairment in WM, increased CT and GI and its correlation with global cognitive functions in visually impaired children suggests cross-modal plasticity due to adaptive compensatory mechanism (as compared to SCs). Reduced CT and increased FA in thalamo-cortical areas in EB suggest synaptic pruning and alteration in WM integrity. In the visual cortical pathway, higher education and the development of blindness modify the morphology of brain areas and influence the probabilistic tractography in EB rather than LB.

Frontal lobe metabolic alterations characterizing Parkinson's disease cognitive impairment.

BACKGROUND AND PURPOSE: Diagnosis of Parkinson's disease (PD) cognitive impairment at early stages is challenging compared to the stage of PD dementia where functional impairment is apparent and easily diagnosed. Hence, to evaluate potential early stage cognitive biomarkers, we assessed frontal lobe metabolic alterations using in vivo multi-voxel proton magnetic resonance spectroscopic imaging (1H-MRSI). METHOD: Frontal metabolism was studied in patients with PD with normal cognition (PD-CN) (n = 26), with cognitive impairment (PD-CI) (n = 27), and healthy controls (HC) (n = 30) using a single slice (two-dimensional) 1H-MRSI at 3 T. The acquired spectra were post-processed distinctly for voxels corresponding to the bilateral middle/superior frontal gray matter (GM) and frontal white matter (WM) regions (delineated employing neuromorphometrics atlas) using the LC-Model software. RESULT: Significant (post hoc p < 0.016) reduction in the concentration of N-acetyl aspartate (NAA) in the middle and superior frontal GMs and total choline (tCho) and total creatine (tCr) in the frontal WM was observed in PD-CI compared to PD-CN and HC, while that in HC and PD-CN groups were comparable. The NAA and tCr/tCho metabolite concentrations showed significant (p < 0.05) positive correlations with cognitive test scores in the frontal GM and WM, respectively. The receiver operating curve (ROC) analysis revealed significant (p < 0.05) "area under curve" for NAA/tNAA in the frontal GM and tCho in the frontal WM. CONCLUSION: The frontal metabolic profile is altered in cognitively impaired PD compared with cognitively normal PD. Neuronal function loss (NAA), altered energy metabolism (Cr), and cholinergic (Cho) neural transmission are implicated in PD cognitive pathology. Frontal neuro-metabolism may promisingly serve as PD cognitive biomarker.

Cortical thickness and gyrification index measuring cognition in Parkinson's disease.

OBJECTIVE: Cortical dynamics is driven by cortico-cortical connectivity and it characterizes cortical morphological features. These brain surface features complement volumetric changes and may offer improved understanding of disease pathophysiology. Hence, present study aims to investigate surface features; cortical thickness (CT) and gyrification index (GI) in Parkinson's disease (PD) patients of normal cognition (PD-CN), cognitively impaired patients with PD (PD-CI) in comparison with cognitively normal healthy controls (HC) to better elucidate cognition linked features in PD. METHOD: Anatomical MRI (3DT1) was carried out in 30 HC (56.53 ± 8.42 years), 30 PD-CN (58.8 ± 6.07 years), and 30 PD-CI (60.3 ± 6.43 years) subjects. Whole brain ROI based parcellation using Desikan-Killiany (DK-40) atlas followed by regional CT and GI differentiation [with 'age' and 'total intracranial volume' (TIV) correction], multiple linear regression (with 'age', 'TIV', and 'education' correction) with clinical variables, ROC analysis, and CT-GI correlation across the groups was used for data analysis. RESULTS: Widespread cortical thinning with regional GI reduction was evident in PD-CI with respect to other two groups (HC and PD-CN), and with absence of such alterations in PD-CN compared to HC. Frontal, parietal, and temporal CT/GI significantly correlated with cognition and presented classification abilities for cognitive state in PD. Mean regional CT and GI were found negatively correlated across groups with heterogeneous regions. CONCLUSION: Fronto-parietal and temporal regions suffer cognition associated cortical thinning and GI reduction. CT may serve better discriminator properties and may be more consistent than GI in studying cognition in PD. Heterogeneous surface dynamics across the groups may signify neuro-developmental alterations in PD.

Evaluation of Memory and Language Network in Children and Adolescents with Visual Impairment: A Combined Functional Connectivity and Voxel-based Morphometry Study.

Functional network changes associated with Braille reading are different in early blind (EB) and late blind (LB) participants. The objectives were to study the functional connectivity (of memory and language areas based on blood oxygen level-dependent [BOLD] mapping) and structural changes in EB and LB children and adolescents. A total of 110 participants (all right-handed) were recruited in two age groups of 6-12 years (children) and 13-19 years (adolescents) consisting of EB (n = 20), LB (n = 20), and sighted controls (SC, n = 15) in each group. Group differences were estimated between children and adolescent groups. Structural changes in visual cortex and medial temporal area, increased BOLD activations and altered functional connectivity in the primary visual cortex, inferior frontal gyrus, middle temporal gyrus, and hippocampus during Braille reading task were observed in adolescents as compared with children blind groups (pFDR corrected <0.05). Functional results were positively correlated with duration of Braille reading and age at onset in EB and LB groups (p ≤ 0.01). Visual, language, and learning memory networks were different in adolescents and children of both EB and LB groups, and also between EB and LB groups suggesting cross-modal plasticity. The functional and structural results revealed education dependent cross-modal plasticity in visually impaired participants. Memory and language network were affected more in the LB group than the EB group, and more in children than adolescents.

Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson's disease and healthy controls.

INTRODUCTION: Parkinson's disease (PD) is a multisystem disorder of unknown etiology, highlights a broad array of symptoms and pathological features influencing organs throughout the body. The metabolic profile of saliva in patients with PD may be influenced by malabsorption in the gastroenteric tract, neurodegeneration, and mitochondrial dysfunction. In the present study, we apply a powerful NMR metabolomics approach for biomarker identification in PD using saliva, a non-invasive bio-fluid. METHODS: Metabolic profiling of saliva were studied in patients with PD (n = 76) and healthy controls (HC, n = 37) were analyzed and differentiated PD from HC. A total of 40 metabolites including aromatic amino acids, short-chain fatty acids, branched chain amino acids, taurine, and N-acetylglutamate were identified. Spectral binned data and concentration of metabolites were estimated for analysis. RESULTS: Increased concentration of phenylalanine, tyrosine, histidine, glycine, acetoacetate, taurine, TMAO, GABA, N-acetylglutamate, acetoin, acetate, alanine, fucose, propionate, isoleucine, and valine were observed in PD as compared to HC. Further, subgroup analysis among early PD, advanced PD, and HC groups, revealed increased metabolite concentration in early PD group as compared to advanced PD and HC group. DISCUSSION: Analysis revealed potential biomarkers and their involvement in amino acid metabolism, energy metabolism, neurotransmitters metabolism, and microflora system. Patients with early PD exhibited higher metabolite concentration as compared to advanced PD group which might be associated with dopaminergic treatment. CONCLUSION: The results of our data indicate that patients with PD might be characterized by metabolic imbalances like gut microflora system, energy metabolites, and neurotransmitters which may contribute to the PD pathogenesis.

Saccadic Eye Movements in Young-Onset Parkinson's Disease - A BOLD fMRI Study.

The objective of the present study was to understand control of saccadic eye movements in patients with young onset Parkinson's disease (YOPD) where onset of disease symptoms appears early in life (<40 years of age). Functional magnetic resonance imaging (fMRI) was performed in patients with YOPD and control subjects while they performed saccadic tasks, which consisted of a reflexive task and another task that required inhibitory control of eye movements (Go-NoGo task). Functional imaging related to saccadic eye movements in this group of patients has not been widely reported. A 1.5T MR scanner was used for structural and functional imaging. Analysis of blood-oxygen-level-dependent (BOLD) fMRI was performed using Statistical Parametric Mapping (SPM) software and compared in patients and controls. In patients with YOPD greater activation was seen significantly in the middle frontal gyrus, medial frontal gyrus, angular gyrus, cingulate gyrus, precuneus and cerebellum, when compared with the control group, during the saccadic tasks. Gap and overlap protocols revealed differential activation patterns. The abnormal activation during reflexive saccades was observed in the overlap condition, while during Go-NoGo saccades in the gap condition. The results suggest that impaired circuitry in patients with YOPD results in recruitment of more cortical areas. This increased frontal and parietal cortical activity possibly reflects compensatory mechanisms for impaired cognitive and saccadic circuitry.

Gray matter biomarkers for major depressive disorder and manic disorder using logistic regression.

The study investigates morphometric changes using surface-based measures and logistic regression in Major depressive-disorder (MDD) and Manic-disorder patients as compared to controls. MDD (n = 21) and manic (n = 20) subjects were recruited from psychiatric clinics, along with 19 healthy-controls from local population, after structured and semi-structured clinical interview (DSM-IV, brief Psychotic-Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton depression rating scale (HDRS), cognitive function by postgraduate Institute Battery of Brain Dysfunction (PGIBBD)). Using 3D T1-weighted images, gray matter (GM) cortical thickness and GM-based morphometric signatures (using logistic regression) were compared among MDD, manic disorder and controls using analysis of covariance (ANCOVA). No significant difference was found between the MDD and manic disorder patients. When compared to controls, cortical thinning was observed in bilateral rostral middle frontal gyrus and parsopercularis, right lateral occipital cortex, right lingual gyrus in MDD; and bilateral rostral middle frontal and superior frontal gyrus, right middle temporal gyrus, left supramarginal and left precentral gyrus in Manic disorders. Logistic regression analysis exhibited GM cortical thinning in the bilateral parsopercularis, right lateral occipital cortex and lingual gyrus in MDD; and bilateral rostral middle, superior frontal gyri, right middle temporal gyrus in Manic with a sensitivity and specificity of 85.7 % and 94.7 % and 90.0 % and 94.7 %, respectively in comparison with controls. Both groups exhibited GM loss in bilateral rostral middle frontal gyrus brain regions compared to controls. Multivariate analysis revealed common changes in GM in MDD and manic disorders associated with mood temperament, but differences when compared to controls.

A Bis(Aquated) Mn(II)-Based MRI Contrast Agent with a Rigid Hydroquinazoline Unit: Synthesis, Characterization, and in Vivo MR Imaging Study.

Since the finding of nephrogenic systemic fibrosis (NFS) in patients with renal impairment and the long-term accumulation of Gd(III) ions in the central nervous system, the search for nongadolinium ion-based MRI contrast agents made of nutrient metal ions has drawn paramount attention. In this context, the development of Mn(II)-based MRI contrast agents has been a subject of interest for the last few decades. Herein, we report a pentadentate ligand (Li2[BenzPic2]) composed of two picolinate moieties and a rigid 1,2,3,4-tetrahydroquinazoline unit and the corresponding bis(aquated) Mn(II) complex (Complex 1). The complex exhibited high thermodynamic stability (log Kcond = 11.62) and kinetic inertness similar to that of the clinically approved Gd(III)-based contrast agent Magnevist. Complex 1 exerted longitudinal relaxivity (r1) of 5.32 mM-1 s-1 at 1.41 T, 37 °C, pH 7.4, and it increased by 3.6-fold in the presence of serum albumin protein, confirming a substantial rigidifying interaction (albumin association constant KA = 1.66 × 103 M-1) between the protein and the amphiphilic (log P = -0.45) contrast agent. An intravenous dose of 0.08 mmol/kg in a healthy mouse, excellent MRI signal intensity enhancement in the vasculature of the mouse liver, and brightened images of the gallbladder, kidney, and liver were realized.

A Novel Kinematic Gait Parameter-Based Vibrotactile Cue for Freezing of Gait Mitigation among Parkinson's Patients: A Pilot Study.

Auditory and visual cues have been efficacious in laboratory-based freezing of gait (FoG) mitigation in Parkinson's disease (PD). However, real-life applications of these cues are restricted due to inconvenience to the users. Closed-loop vibrotactile cues based on temporal gait events have overcome the shortcomings of auditory and visual cueing. However, kinematic gait parameter-driven vibrotactile cueing has not been explored yet. Kinematic gait parameter-driven cueing is more effective than temporal cueing, according to FoG pathophysiology studies. Therefore, we developed and pilot-tested a novel cueing scheme in which the foot-to-ground angle at heel strike (FGA_HS) is estimated using indigenous instrumented shoes to drive vibrotactile cueing. Ten PD freezers underwent a 6-meter timed walk test in the off-medication state with and without the cue and after medication without the cue. The proposed system potentially mitigated FoG, quantified by a reduction in the ratio of time spent freezing to the total walking time and the number of FoGs. The FoG mitigation potential of the cue was further supported by increased anteroposterior center of pressure progression and FGA_HS. With a future comprehensive validation in a larger number of participants, the novel cue could likely be used in practice and commercialized.

Alkyl Chain Appended Fe(III) Catecholate Complex as a Dual-Modal T1 MRI-NIR Fluorescence Imaging Agent via Second Sphere Water Interactions.

The C12-alkyl chain-conjugated Fe(III) catecholate complex [Fe(C12CAT)3]3-, Fe(C12CAT)3 [C12CAT = N-(3,4-dihydroxyphenethyl)dodecanamide], was synthesized and characterized, reported as a dual-modal T1-MRI and an optical imaging probe. The DFT-optimized structure of Fe(C12CAT)3 reveals a distorted octahedral coordination geometry around the high spin Fe(III) center. The formation constant (-log K) of Fe(C12CAT)3 was calculated as 45.4. The complex exhibited r1-relaxivity values of 2.31 ± 0.12 and 1.52 ± 0.06 mM-1 s-1 at 25 and 37 °C, respectively, on 1.41 T at pH 7.3 via second-sphere water interactions. The interaction of Fe(C12CAT)3 with human serum albumin showed concomitant enhancement of r1-relaxivity to 6.44 ± 0.15 mM-1 s-1. The MR phantom images are significantly brighter and directly correlate to the concentration of Fe(C12CAT)3. Adding an external fluorescent marker IR780 dye to Fe(C12CAT)3 leads to the formation of self-assembly by C12-alkyl chains. It resulted in the fluorescence quenching of the dye, and its critical aggregation concentration was calculated as 70 µM. The aggregated matrix of Fe(C12CAT)3 and IR780 dye is spherical, with an average hydrodynamic diameter of 189.5 nm. This self-assembled supramolecular system is found to be non-fluorescent and was "turn-on" under acidic pH via dissociation of aggregates. The r1-relaxivity is found to be unchanged during the matrix aggregation and disaggregation. The probe showed MRI ON and fluorescent OFF under physiological conditions and MRI ON and fluorescent ON under acidic pH. The cell viability experiments showed that the cells are 80% viable at 1 mM probe concentration. Fluorescence experiments and MR phantom images showed that Fe(C12CAT)3 is a potential dual model imaging probe to visualize the acidic pH environment of the cells.

Reducing Stress with Yoga: A Systematic Review Based on Multimodal Biosignals.

Stress is an enormous concern in our culture because it is the root cause of many health issues. Yoga asanas and mindfulness-based practices are becoming increasingly popular for stress management; nevertheless, the biological effect of these practices on stress reactivity is still a research domain. The purpose of this review is to emphasize various biosignals that reflect stress reduction through various yoga-based practices. A comprehensive synthesis of numerous prior investigations in the existing literature was conducted. These investigations undertook a thorough examination of numerous biosignals. Various features are extracted from these signals, which are further explored to reflect the effectiveness of yoga practice in stress reduction. The multifaceted character of stress and the extensive research undertaken in this field indicate that the proposed approach would rely on multiple modalities. The notable growth of the body of literature pertaining to prospective yoga processes is deserving of attention; nonetheless, there exists a scarcity of research undertaken on these mechanisms. Hence, it is recommended that future studies adopt more stringent yoga methods and ensure the incorporation of suitable participant cohorts.

Effect of rTMS at SMA on task-based connectivity in PD.

BACKGROUND: Transcranial magnetic stimulation (TMS) can aid in alleviating clinical symptoms in Parkinson's disease (PD). To better understand the neural mechanism of the intervention, neuroimaging modalities have been used to assess the effects of rTMS. OBJECTIVE: To study the changes in cortical connectivity and motor performance with rTMS at supplementary motor area (SMA) in PD using clinical assessment tools and task-based functional MRI. METHODOLOGY: 3000 pulses at 5 Hz TMS were delivered at the left SMA once a week for a total of 8 consecutive weeks in 4 sham sessions (week 1-4) and 4 real sessions (week 5 to week 8) in 16 subjects with PD. The outcomes were assessed with UPDRS, PDQ 39 and task-based fMRI at baseline, after sham sessions at week 4, and after real sessions at week 8. Visuo-spatial functional MRI task along with T1 weighted scans (at 3 Tesla) were used to evaluate the effects of rTMS intervention. Multivariate pattern analysis (MVPA) was used to analyse task-based fMRI using Conn toolbox. RESULTS: Improvements (p < 0.05) were observed in UPDRS II, III, Mobility and ADL of PDQ39 after real sessions of rTMS. MVPA of task-based connectivity revealed clusters of activation in right hemispheric precentral area, superior frontal gyrus, middle frontal gyrus, thalamus and cerebellum (cluster threshold pFDR=0.001). CONCLUSIONS: Weekly rTMS sessions at SMA incurred clinical motor benefits as revealed by an improvement in clinical scales and dexterity performance. These benefits could be attributed to changes in connectivity remote brain regions in the motor network.

Elevated choline in dorsolateral prefrontal cortex of lithium responders with bipolar I disorder.

INTRODUCTION: Response to lithium maintenance varies widely across patients with bipolar disorder (BD). The studies on neurochemical correlates of long-term lithium response in BD remain scant. AIM: To assess the neurochemical profile in DLPFC based on lithium response status among subjects with bipolar I disorder (BD-I) using in vivo MRS. MATERIALS AND METHOD: This was an observational study of 40 right-handed, euthymic adult participants with DSM-5 BD-I on long-term lithium maintenance with no psychiatric comorbidities (MINI 7.0). Using Alda Lithium Response Scale (LRS), a cut-off ≥ 7 for excellent lithium response, the sample was grouped into study group I for responders and group II for non-responders. All participants were assessed using NIMH Life Chart Method and IGSLI typical/atypical features scale. 1H-MRS was carried out on a 3 T MR scanner (Achieva, Phillips) using a 32-channel head coil, with a voxel placed at the left DLPFC. LC model was used to measure absolute concentrations of neurochemicals and their ratios in relation to creatine. RESULTS: Group I (n = 20) was comparable to Group II (n = 20) with respect to demographic and illness profile. The GPC/Cr+PCr ratio was significantly higher (p = 0.028) among excellent lithium responders (0.32 ± 0.20 mmol/l) compared to sub-optimal responders (0.25 ± 0.05 mmol/l). Choline-containing compounds reflect alterations in cell membrane synthesis or myelin turnover, and are a marker of overall cell density. No significant alterations were detected in NAA, glutamate, glutamine, myo-inositol and creatine. CONCLUSION: The lithium responders exhibited elevated choline (GPC) in the left DLPFC compared to non-responders.

Mechanisms of 1 Hz Inhibitory and 5 Hz Excitatory Repetitive Transcranial Magnetic Stimulations in Parkinson's Disease: A Functional Magnetic Resonance Imaging Study.

Background: Parkinson's disease (PD) is a progressive disorder with alterations in cortical functional activity. Transcranial magnetic stimulation is known to incur motor benefits in PD by inducing motor activity through cortical connectivity, although the mechanisms are unclear. Objective: The effects of repetitive transcranial magnetic stimulation (rTMS) (at three cortical sites) on functional and structural plasticity were studied in PD to understand inhibitory or excitatory rTMS-induced motor improvement. Methodology: The study was a single blind, randomized, sham-controlled type involving three groups. Three thousand rTMS pulses of frequency 1 Hz were given at primary motor area (in 13 patients of Group A) or premotor area (in Group B, n = 18) and a frequency 5 Hz at supplementary motor area in Group C (n = 19). Clinical rating scores (Unified Parkinson's Disease Rating Scale [UPDRS], Parkinson's Disease Questionaire-39 [PDQ-39]) and motor dexterity were assessed at baseline, after sham and real rTMS sessions. Visuospatial functional magnetic resonance imaging task along with T1-weighted scans (at three Tesla) were used to evaluate the motor execution and planning post rTMS intervention. Results: Improvements (p < 0.05) in UPDRS II, III, Mobility, and activities of daily living of PDQ-39, Purdue Pegboard were observed. Increased blood oxygen level-dependent (BOLD) activations (family-wise error [FWE]-corrected P-value [pFWE] <0.01) were observed in motor cortices, parietal association areas, and cerebellum in groups C and decrease in group A and B after real TMS as compared with sham. Conclusions: Repetitive TMS at motor (1 Hz) and supplementary motor (5 Hz) areas resulted in significant clinical benefits by inducing cortical plasticity. Impact statement TMS daily protocols have been commonly employed to modulate cortical connectivity in Parkinson's disease (PD). This study uses functional magnetic resonance imaging to assess rTMS-related effects in PD. Repetitive TMS protocol at higher pulses (3000/session) in primary and supplementary motor cortices administered weekly was clinically effective and safe. The results revealed functional restoration along with cortical plasticity mechanisms of externally generated movement in PD in response to noninvasive brain stimulation.

Mn(II) complex impregnated porous silica nanoparticles as Zn(II)-responsive "Smart" MRI contrast agent for pancreas imaging.

Type-1 and type-2 diabetes mellitus are metabolic disorders governed by the functional efficiency of pancreatic ß-cells. The activities of the cells toward insulin production, storage, and secretion are accompanied by Zn(II) ions. Thus, for non-invasive pathology of the cell, developing Zn(II) ion-responsive MRI-contrast agents has earned considerable interest. In this report, we have synthesized a seven-coordinate, mono(aquated) Mn(II) complex (1), which is impregnated within a porous silica nanosphere of size 13.2 nm to engender the Mn(II)-based MRI contrast agent, complex 1@SiO2NP. The surface functionalization of the nanosphere by the Py2Pic organic moiety for the selective binding of Zn(II)-ions yields complex 1@SiO2-Py2PicNP, which exhibits r1 = 13.19 mM-1 s-1. The relaxivity value elevates to 20.38 mM-1 s-1 in the presence of 0.6 mM BSA protein at pH 7.4. Gratifyingly, r1 increases linearly with the increase of Zn(II) ion concentration and reaches 39.01 mM-1 s-1 in the presence of a 40 fold excess of the ions. Thus, Zn(II)-responsive contrast enhancement in vivo is envisaged by employing the nanoparticle. Indeed, a contrast enhancement in the pancreas is observed when complex 1@SiO2-Py2PicNP and a glucose stimulus are administered in fasted healthy C57BL/6 mice at 7 T.

PGC-1α Agonist Rescues Doxorubicin-Induced Cardiomyopathy by Mitigating the Oxidative Stress and Necroptosis.

Cardiomyopathy (particularly dilated cardiomyopathy (DCM)) significantly contributes to development and progression of heart failure (HF), and inflammatory factors further deteriorate the symptoms. Morphological and functional defects of the heart in doxorubicin (DOX)-induced cardiomyopathy (cardiotoxicity) are similar to those of DCM. We used anagonist of PGC-1α (PPAR (peroxisome proliferator-activated receptor-gamma)-γ coactivator-1α) that is considered as the 'master regulator' of mitochondrial biogenesis with an aim to rescue the DOX-induced deleterious effects on the heart. Forty male C57BL/6J mice (8 weeks old) were divided in four groups, Control, DOX, ZLN005, and ZLN005 + DOX (n = 10 each group). The DOX-induced (10 mg/kg, single dose) cardiomyopathy mimics a DCM-like phenotype with marked morphologic alteration in cardiac tissue and functional derangements. Significant increased staining was observed for Masson Trichrome/Picrosirius red and α-Smooth Muscle Actinin (α-SMA) that indicated enhanced fibrosis in the DOX group compared to the control that was attenuated by (peroxisome proliferator-activated receptor-gamma (PPAR-γ) coactivator) (PGC)-1α (alpha) agonist (four doses of 2.5 mg/kg/dose; cumulative dose = 10 mg/kg). Similarly, elevated expression of necroptosis markers along with enhanced oxidative stress in the DOX group were alleviated by PGC-1α agonist. These data collectively suggested the potent therapeutic efficacy of PGC-1α agonist in mitigating the deleterious effects of DOX-induced cardiomyopathy, and it may be targeted in developing the future therapeutics for the management of DCM/HF.

Gd/hafnium oxide@gold@chitosan core-shell nanoparticles as a platform for multimodal theranostics in oncology research.

In the current study, we synthesized thiolated chitosan-stabilized gold-coated, gadolinium-doped hafnium oxide nanoparticles (CAuGH NPs) with the capability of acting as a multifunctional system to deliver anticancer drug doxorubicin (DOX), to enhance radiosensitization by ROS generation, and to provide magnetic resonance (MR) imaging contrast for biomedical applications.

Post-Stroke Rehabilitation of Distal Upper Limb with New Perspective Technologies: Virtual Reality and Repetitive Transcranial Magnetic Stimulation-A Mini Review.

Upper extremity motor impairment is the most common sequelae in patients with stroke. Moreover, its continual nature limits the optimal functioning of patients in the activities of daily living. Because of the intrinsic limitations in the conventional form of rehabilitation, the rehabilitation applications have been expanded to technology-driven solutions, such as Virtual Reality and Repetitive Transcranial Magnetic Stimulation (rTMS). The motor relearning processes are influenced by variables, such as task specificity, motivation, and feedback provision, and a VR environment in the form of interactive games could provide novel and motivating customized training solutions for better post-stroke upper limb motor improvement. rTMS being a precise non-invasive brain stimulation method with good control of stimulation parameters, has the potential to facilitate neuroplasticity and hence a good recovery. Although several studies have discussed these forms of approaches and their underlying mechanisms, only a few of them have specifically summarized the synergistic applications of these paradigms. To bridge the gaps, this mini review presents recent research and focuses precisely on the applications of VR and rTMS in distal upper limb rehabilitation. It is anticipated that this article will provide a better representation of the role of VR and rTMS in distal joint upper limb rehabilitation in patients with stroke.