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.

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.

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.

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.

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.

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.

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.

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.

Evaluation of structural brain changes and their correlation with cognitive functions in adults with type 1 diabetes stratified by the age of diabetes onset: A cross-sectional study.

BACKGROUND AND AIM: T1DM has a significant effect on brain structure and function. Age of onset of diabetes may be a critical factor mediating this impairment. We evaluated young adults with T1DM, stratified by the age of onset, for structural brain changes, hypothesizing that there may be a spectrum of white matter damage in these participants, compared to controls. METHODS: We recruited adult patients (20-50 years of age at the time of study enrolment) with onset of T1DM before 18 years of age and at least ten years of schooling, along with controls having normoglycaemia. We compared the Diffusion Tensor Imaging parameters between patients and controls and evaluated their correlations with cognitive z scores, and glycemic measures. RESULTS: We evaluated 93 individuals, 69 [age: 24.1 (±4.5) years, gender: 47.8% men, education: 14.7 ± 1.6 years] with T1DM and 24 [age: 27.8 (±5.4) years, gender: 58.3% men, education: 14.6 ± 1.9 years] without T1DM (controls). We did not find any significant correlation of fractional anisotropy (FA) with age at T1D diagnosis, duration of diabetes, current glycemic status, or domain-wise cognitive z scores. The FA was lower (but not statistically significant) in participants with T1DM when evaluated for the whole brain, individual lobes, hippocampi and amygdala. CONCLUSION: Participants with T1DM do not show a significant difference in the brain white matter integrity when evaluated in a cohort of young adults with relatively few microvascular complications compared to controls.

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.

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.

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.

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.

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.

Auditory perception of ambiguous and non-ambiguous sound in early and late blind children: A functional connectivity study.

INTRODUCTION: Auditory perception and associated cognition involve visual and auditory cortical areas for inference of meaningful soundscape. OBJECTIVE: To investigate auditory perception of ambiguous and non-ambiguous stimulation in auditory and visual cortical networks for categorical discrimination. METHODOLOGY: Functional mapping was carried out in twenty early (EB), twenty late blind (LB) and fifteen healthy children, during auditory ambiguous and non-ambiguous stimulation task in a 3 T MR scanner to estimate hemodynamic signal alteration and its effect on functional connectivity. The degree of amplitude low-frequency fluctuation (ALFF), correlation analysis and multiple comparison was carried out to map the impact of duration of education and onset of blindness (EB and LB). RESULTS AND DISCUSSION: Increased functional connectivity (FC) and cross-modal reorganization was observed in auditory, visual and language networks in EB children. FC was increased in contralateral hemisphere in both the blind children (EB and LB) groups and was positively correlated with duration of education performance. Cognitive assessment scores correlated (p < 0.01) with cluster coefficient of FC and BOLD response. CONCLUSION: FC alterations depend on onset age and audio-haptic training in children associated with increased auditory language and memory perception.

Comparing cognition, coping skills and vedic personality of individuals practicing yoga, physical exercise or sedentary lifestyle: a cross-sectional fMRI study.

BACKGROUND: Nature and intensity of physical activity may influence cognition, coping mechanisms and overall personality of an individual. The objective of this cross-sectional study was to compare cognition, coping styles and vedic personality among individuals practicing different lifestyle. METHODS: Thirty-nine healthy young adults of both gender (27.63±4.04 years) were recruited and categorized into three groups; i.e. yoga, physical activity or sedentary lifestyle groups. Participants were assessed on cognition, coping styles and Vedic personality inventory (VPI). Verbal-n-back and Stroop tasks were performed using 3 Tesla MRI scanner. Task Based Connectivity (TBC) analysis was done using CONN toolbox in SPM. RESULTS: There were no significant differences in the cognitive domains across the groups. The planning (p=0.03) and acceptance domain (p=0.03) of the Brief COPE scale showed difference across the groups. Post-hoc analysis revealed that planning and acceptance scores were distinctly higher in the physical activity group, however, there was no difference between physical activity group and yoga practitioners. Similarly, in the VPI, Sattva (p=0.003), Rajas (p=0.05) and Tamas (p=0.01) were different across the groups, and the post hoc analysis showed superiority in Sattva scores in Yoga group, meanwhile, both Rajas and Tamas were higher in the physical activity group. Yoga practitioners preferentially recruited left Superior Frontal Gyrus in relation to the physically active group and precuneus in relation to the sedentary lifestyle group. CONCLUSION: The study revealed that yoga practitioners had a distinct higher sattva guna and preferentially recruited brain areas associated with self-regulation and inhibitory control.

Mn(II) complexes of phenylenediamine based macrocyclic ligands as T1-MRI contrast agents.

The Mn(II) complexes are emerging as alternative T1-MRI contrast agents (CAs) to the currently available Gd-based CAs. The complexes [Mn(L1)] 1 and [Mn(L2)] 2 of o-phenylenediamine based macrocyclic ligands are reported as T1-CAs for MRI applications. The high spin state of the Mn(II) complexes (S = 5/2) is confirmed by EPR spectra. The complexes showed an irreversible Mn(II)/Mn(III) redox potential at pH 7.28, which became more and less positive at the acidic and alkaline pHs, respectively. The species [MnL], [Mn(LH-1), and [Mn(LH-2) are persisted in solution. Complex 1 is inert towards Ca(II), Mg(II), and Zn(II), whereas complex 2 is inert for Ca(II) and Mg(II) and labile under Zn(II) and Cu(II) ions. Complex 1 showed an r1-relaxivity of 3.27 and 2.32 mM-1 s-1 at 1.41 T, 25, and 37 °C respectively via inner-sphere water relaxation, which is lower than that of 2 (r1, 5.56, and 4.19 mM-1 s-1) at pH 7.28 and 1.41 T. The Mn(II) complexes showed a 2-8% enhancement of r1-relaxivity while lowering the pH to acidic, which corresponds to the release of free Mn(II) ions. In contrast, the r1-relaxivity is dropped to 52% and 20% for 1 and 2 respectively under alkaline pH due to the deprotonation of inner-sphere water. Phantom images obtained on Bruker 'BIOSPEC' 47/40 animal research MRI/MRS scanner showed concentration-dependent brightness. The interaction of human serum albumin (HSA) with 1 and 2 exhibited five times higher r1-relaxivities (11.3 and 22.0 mM-1 s-1 at 1.41 T, respectively).

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.

Imaging application and radiosensitivity enhancement of pectin decorated multifunctional magnetic nanoparticles in cancer therapy.

In this contribution, we report the fabrication of multifunctional nanoparticles with gold shell over an iron oxide nanoparticles (INPs) core. The fabricated system combines the magnetic property of INPs and the surface plasmon resonance of gold. The developed nanoparticles are coated with thiolated pectin (TPGINs), which provides stability to the nanoparticles dispersion and allows the loading of hydrophobic anticancer drugs. Curcumin (Cur) is used as the model drug and an encapsulation efficiency of approximately 80% in TPGINs is observed. Cytotoxicity study with HeLa cells shows that Cur-loaded TPGINs have better viability percent (~30%) than Cur alone (~40%) at a dose of 30 µg of TPGINs. Further, annexin V-PI assay demonstrated the enhanced anticancer activity of Cur-loaded TPGINs via induction of apoptosis. The use of TPGINs leads to a significant enhancement in generating reactive oxygen species (ROS) in HeLa cells through improved radiosensitization by gamma irradiation (0.5 Gy). TPGINs are further evaluated for imparting contrast in magnetic resonance imaging (MRI) with the r2 relaxivity in the range of 11.06-13.94 s-1 µg-1 mL when measured at 7 Tesla. These experimental results indicate the potential of TPGINs for drug delivery and MR imaging.