Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. METHODS: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. RESULTS: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. CONCLUSIONS: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

One-pot synthesis of g-C3N4/N-doped CeO2 nanocomposites and their potential visible light-driven photocatalytic degradation of methylene blue dye.

In the pursuit of efficient photocatalytic materials for environmental applications, a new series of g-C3N4/N-doped CeO2 nanocomposites (g-C3N4/N-CeO2 NCs) was synthesized using a straightforward dispersion method. These nanocomposites were systematically characterized to understand their structural, optical, and chemical properties. The photocatalytic performance of g-C3N4/N-CeO2 NCs was evaluated by investigating their ability to degrade methylene blue (MB) dye, a model organic pollutant. The results demonstrate that the integration of g-C3N4 with N-doped CeO2 NCs reduces the optical energy gap compared to pristine N-doped CeO2, leading to enhanced photocatalytic efficiency. It is benefited from the existence of g-C3N4/N-CeO2 NCs not only in promoting the charge separation and inhibits the fast charge recombination but also in improving photocatalytic oxidation performance. Hence, this study highlights the potential of g-C3N4/N-CeO2 NCs as promising candidates for various photocatalytic applications, contributing to the advancement of sustainable environmental remediation technologies.

Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium.

Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.

5-HT1A targeting PARCEST agent DO3AM-MPP with potential for receptor imaging: Synthesis, physico-chemical and MR studies.

Contrast enhancement in MRI using magnetization or saturation transfer techniques promises better sensitivity, and faster acquisition compared to T1 or T2 contrast. This work reports the synthesis and evaluation of 5-HT1A targeted PARACEST MRI contrast agent using 1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide (DO3AM) as the bifunctional chelator, and 5-HT1A-antagonist methoxyphenyl piperazine (MPP) as a targeting unit. The multi-step synthesis led to the MPP conjugated DO3AM with 60% yield. CEST-related physicochemical parameters were evaluated after loading DO3AM-MPP with paramagnetic MRI active lanthanides: Gadolinium (Gd-DO3AM-MPP) and Europium (Eu-DO3AM-MPP). Luminescence lifetime measurements with Eu-DO3AM-MPP and computational DFT studies using Gd-DO3AM-MPP revealed the coordination of one water molecule (q = 1.43) with metal-water distance (rM-H2O) of 2.7 Å and water residence time (τm) of 0.23 ms. The dissociation constant of Kd 62 ± 0.02 pM as evaluated from fluorescence quenching of 5-HT1A (protein) and docking score of -4.81 in theoretical evaluation reflect the binding potential of the complex Gd-DO3AM-MPP with the receptor 5-HT1A. Insights of the docked pose reflect the importance of NH2 (amide) and aromatic ring in Gd-DO3AM-MPP while interacting with Ser 374 and Phe 370 in the antagonist binding pocket of 5-HT1A. Gd-DO3AM-MPP shows longitudinal relaxivity 5.85 mM-1s-1 with a water residence lifetime of 0.93 ms in hippocampal homogenate containing 5-HT1A. The potentiometric titration of DO3AM-MPP showed strong selectivity for Gd3+ over physiological metal ions such as Zn2+ and Cu2+. The in vitro and in vivo studies confirmed the minimal cytotoxicity and presential binding of Gd-DO3AM-MPP with 5-HT1A receptor in the hippocampus region of the mice. Summarizing, the complex Gd-DO3AM-MPP can have a potential for CEST imaging of 5-HT1A receptors.

FDG PET-CT findings of extra-thoracic sarcoid are associated with cardiac sarcoid: A rationale for using FGD PET-CT for cardiac sarcoid evaluation.

PURPOSE: This retrospective study investigates the relationship between cardiac and extra-thoracic sarcoid findings on FDG PET-CT using a 72-hour pretest high-fat, high-protein, and very low-carbohydrate (HFHPVLC) diet. PATIENTS AND METHODS: A total of 196 consecutive FDG PET-CT scans with 72-hour HFHPVLC diet preparation were performed between December 2014 and December 2015 in known sarcoid patients. Of these scans, 5 were excluded for non-adherence to diet preparation or underlying cancer. Cardiac and extra-thoracic sarcoid lesions were categorized and measured for radiotracer uptake. RESULTS: A total of 188 patients had 191 eligible FDG PET/CT scans (3 follow-up scans), of which there were 20 (10%) positive, 6 indeterminate (3%), and 165 (86%) negative for CS. Among the 20 scans positive for CS, 8 (40%) had findings of both cardiac and extra-thoracic sarcoid. CONCLUSION: Our study shows that 40% of CS patients also have FDG PET-CT findings of extra-thoracic sarcoid. This makes an intriguing case for FDG PET-CT use with pretest diet prep over cardiac MRI (CMR) for cardiac sarcoid evaluation, given that CMR is likely to overlook these extra-thoracic sites of disease.

The Mental Health Acute Assessment Team: a collaborative approach to treating mental health patients in the community.

OBJECTIVE: Many models of community-based mental health crisis teams have been reported. We present our experience of an outreach team made up of a paramedic and mental health nurse. METHODS: A proof-of-concept was conducted in Western Sydney. The primary outcome was the proportion of patients where the team were able to facilitate the most appropriate care. RESULTS: Nearly 70% of patients were able to be treated outside the Emergency Department, with about two-thirds being transported directly to a mental health facility. CONCLUSION: We have demonstrated that our model of care is successful in enabling appropriate physical and mental health care for patients suffering an acute mental health crisis.

BOLD fMRI and DTI in strabismic amblyopes following occlusion therapy.

Evaluation of brain cluster activation using the functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was sought in strabismic amblyopes. In this hospital-based case-control cross-sectional study, fMRI and DTI were conducted in strabismic amblyopes before initiation of any therapy and after visual recovery following the administration of occlusion therapy. FMRI was performed in 10 strabismic amblyopic subjects (baseline group) and in 5 left strabismic amblyopic children post-occlusion therapy after two-line visual improvement. Ten age-matched healthy children with right ocular dominance formed control group. Structural and functional MRI was carried out on 1.5T MR scanner. The visual task consisted of 8 Hz flickering checkerboard with red dot and occasional green dot. Blood-oxygen-level-dependent (BOLD) fMRI was analyzed using statistical parametric mapping and DTI on NordicIce (NordicNeuroLab) softwares. Reduced occipital activation was elicited when viewing with the amblyopic eye in amblyopes. An 'ipsilateral to viewing eye' pattern of calcarine BOLD activation was observed in controls and left amblyopes. Activation of cortical areas associated with visual processing differed in relation to the viewing eye. Following visual recovery on occlusion therapy, enhanced activity in bilateral hemispheres in striate as well as extrastriate regions when viewing with either eye was seen. Improvement in visual acuity following occlusion therapy correlates with hemodynamic activity in amblyopes.

The role of IL-15 in activating STAT5 and fine-tuning IL-17A production in CD4 T lymphocytes.

IL-15 is an important IL-2-related cytokine whose role in Th17 cell biology has not been fully elucidated. In this study, we show that exogenous IL-15 decreased IL-17A production in Th17 cultures. Neutralization of IL-15 using an Ab led to increases in IL-17A production in Th17 cultures. Both Il15(-/-) and Il15r(-/-) T cell cultures displayed higher frequency of IL-17A producers and higher amounts of IL-17A in the supernatants compared with those of wild-type (WT) cells in vitro. IL-15 down-modulated IL-17A production independently of retinoic acid-related orphan receptor-γt, Foxp3, and IFN-γ expression. Both Th17 cells and APCs produced IL-15, which induced binding of STAT5, an apparent repressor to the Il17 locus in CD4 T cells. Also, in a model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), Il15(-/-) mice displayed exacerbated inflammation-correlating with increased IL-17A production by their CD4(+) T cells-compared with WT controls. Exogenous IL-15 administration and IL-17A neutralization reduced the severity of EAE in Il15(-/-) mice. Taken together, these data indicate that IL-15 has a negative regulatory role in fine-tuning of IL-17A production and Th17-mediated inflammation.

A comprehensive review to assess the potential, health benefits and complications of fucoidan for developing as functional ingredient and nutraceutical.

Polysaccharides from seaweeds or macroalgae are garnering significant interest from pharmaceutical and food industries due to their bioactivities and promising therapeutic effects. Among the diverse agal polysaccharides, fucoidan is a well-documented and stands out as a well-researched sulphated heteropolysaccharide found in brown seaweeds. It primarily consists of l-fucose and sulfate ester groups, along with other monosaccharides like xylose, mannose, uronic acid, rhamnose, arabinose, and galactose. Recent scientific investigations have unveiled the formidable inhibitory prowess of fucoidan against SARS-CoV-2, offering a promising avenue for therapeutic intervention in our current landscape. Moreover, fucoidan has demonstrated remarkable abilities in safeguarding the gastrointestinal tract, regulating angiogenesis, mitigating metabolic syndrome, and fortifying bone health. Despite the abundance of studies underscoring fucoidan's potential as a vital component sourced from nature, its exploitation remains constrained by inherent limitations. Thus, the primary objective of this article is to furnish a comprehensive discourse on the structural attributes, health-enhancing properties, safety parameters, and potential toxicity associated with fucoidan. Furthermore, the discourse extends to elucidating the practical applications and developmental prospects of fucoidan as a cornerstone in the realm of functional foods and nutraceuticals.

Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium.

Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.

Conditional ablation of the Notch2 receptor in the ocular lens.

Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors have not been investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, denucleation defects, and cataracts. Notch2 mutants also had persistent lens stalks as early as E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed that upon loss of Notch2, there were elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2), and Trp63 (p63) that negatively regulates Wnt signaling, plus down-regulation of Cdh1 (E-Cadherin). Removal of Notch2 also resulted in an increased proportion of fiber cells, as was found in Rbpj and Jag1 conditional mutant lenses. However, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. We found that Notch2 normally blocks lens progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation.

Smart Contract Authentication assisted GraphMap-Based HL7 FHIR architecture for interoperable e-healthcare system.

The exponential growth in the global population and significant advancements in healthcare broadened the scope of intervention for e-Healthcare through decentralized data access and information exchange, making complex clinical decisions. e-Healthcare can perform several functionalities, including EHR communication, telemedicine, and complex clinical decision systems (CCDS), but large-scale users still find it challenging to maintain interoperability, stability, and scalability. Accommodating an extensive array of stakeholders, which includes patients, doctors, hospitals, and laboratories, demands interoperability to serve scalable services. FHIR frameworks have played a vital role in e-Healthcare designs. Most of the existing HL7-FHIR frameworks have used REST-API using HTTP-query for CRUD tasks that impose numerous rules and constraints, making the process more complex and time-consuming, violating the quality-of-service (QoS) standards on different levels. This paper develops a novel, robust Smart-Contract Authentication Assisted HL7-FHIR framework toward an interoperable e-Healthcare solution. Unlike classical REST API-based FHIR, our proposed method applies a Graph-mapping concept that transforms each resource variable into an equivalent Graph-Mapped Data Structure (GMS), which is subsequently stored in the NoSQL MongoDB database, reducing computational costs and time to meet QoS demands. The proposed model employs three key components, GMS-driven HL7 FHIR Gateway Model, Smart Contract Authentication and Client Model. The Smart Contract function helped verify and authenticate users to ensure privacy and secure EHR exchange. The assessment of the performance of the proposed model reveals a significant reduction in computational time with optimal resource utilization making it a significant and viable option to better the real-world e-Healthcare mechanisms.

fMRI Analysis of Dissociative Convulsions: A Case-Controlled Study.

Background and Objectives: Dissociative convulsions represent complex biopsychosocial etiopathogenesis and have semiological similarities with epilepsy, which leads to delays in definitive diagnosis as well as treatment. We explored the neurobiological underpinnings of dissociative convulsions using a functional magnetic resonance imaging (fMRI) design targeting cognitive, affective, and resting state characteristics in our subjects. Materials and Methods: Seventeen female patients with dissociative convulsions without any co-morbid psychiatric or neurological illness and 17 matched healthy controls underwent standardized task-based (affective and cognitive) and resting state fMRI. Blood oxygen level-dependent (BOLD) activation results were compared across the groups, and correlation with the severity of dissociation was measured. Results: Patients with dissociative convulsions had lower activation in the left cingulate gyrus, left paracentral lobule, right middle and inferior frontal gyrus, right caudate nucleus, and right thalamus. There was increased resting state functional connectivity (FC) between the left posterior superior temporal gyrus and left superior parietal lobule; left amygdala and Default Mode Network (DMN) of right lateral parietal cortex; right supramarginal gyrus and left cuneus in the patient group. Patients also had decreased FC between the anterior cingulate cortex (ACC) and left thalamus; ACC and right central opercular cortex; DMN of PCC, posterior cingulate gyrus, and right middle temporal lobe. Conclusions: Patients with dissociative convulsions have significant deficits in the areas associated with the processing of emotional, cognitive, memory, and sensory-motor functions. There is a significant correlation between dissociative severity and the functioning of areas involving the processing of emotions, cognition, and memory.

Neural interface of mirror therapy in chronic stroke patients: a functional magnetic resonance imaging study.

BACKGROUND: Recovery in stroke is mediated by neural plasticity. Neuro-restorative therapies improve recovery after stroke by promoting repair and function. Mirror neuron system (MNS) has been studied widely in humans in stroke and phantom sensations. MATERIALS AND METHODS: Study subjects included 20 patients with chronic stroke and 10 healthy controls. Patients had clinical disease-severity scores, functional magnetic resonance imaging (fMRI) and diffuse tensor imaging (DTI) at baseline, 8 and at 24 weeks. Block design with alternate baseline and activation cycles was used with a total of 90 whole brain echo planar imaging (EPI) measurements (timed repetition (TR) = 4520 ms, timed echo (TE) = 44 ms, slices = 31, slice thickness = 4 mm, EPI factor 127, matrix = 128 × 128, FOV = 230 mm). Whole brain T1-weighted images were acquired using 3D sequence (MPRage) with 120 contiguous slices of 1.0 mm thickness. The mirror therapy was aimed via laptop system integrated with web camera, mirroring the movement of the unaffected hand. This therapy was administered for 5 days in a week for 60-90 min for 8 weeks. RESULTS: All the patients showed statistical significant improvement in Fugl Meyer and modified Barthel Index (P < 0.05) whereas the change in Medical Research Council (MRC) power grade was not significant post-therapy (8 weeks). There was an increase in the laterality index (LI) of ipsilesional BA 4 and BA 6 at 8 weeks exhibiting recruitment and focusing principles of neural plasticity. CONCLUSIONS: Mirror therapy simulated the "action-observation" hypothesis exhibiting recovery in patients with chronic stroke. Therapy induced cortical reorganization was also observed from our study.

Dynamic Data Infrastructure Security for Interoperable e-Healthcare Systems: A Semantic Feature-Driven NoSQL Intrusion Attack Detection Model.

The exponential rise in advanced software computing and low-cost hardware has broadened the horizon for the Internet of Medical Things (IoMT), interoperable e-Healthcare systems serving varied purposes including electronic healthcare records (EHRs) and telemedicine. However, being heterogeneous and dynamic in nature, their database security remains a challenge forever. Numerous intrusion attacks including bot-attack and malware have confined major classical databases towards e-Healthcare. Despite the robustness of NoSQL over the structured query language databases, the dynamic data nature over a heterogeneous environment makes it vulnerable to intrusion attacks, especially over interoperable e-Healthcare systems. Considering these challenges, this work proposed a first of its kind semantic feature-driven NoSQL intrusion attack (NoSQL-IA) detection model for interoperable e-Healthcare systems. This work assessed the efficacy of the different semantic feature-extraction methods like Word2Vec, Continuous Bag of Words, N-Skip Gram (SKG), Count Vectorizer, TF-IDF, and GLOVE towards NoSQL-IA prediction. Subsequently, to minimize computational exhaustion, different feature selection methods including Wilcoxon Rank Sum Test (WRST), significant predictor test, principal component analysis, Select K-Best, and variance threshold feature selection algorithms were employed. To alleviate the data imbalance problem, it applied different resampling methods including upsampling, downsampling, and synthetic minority oversampling technique (SMOTE) over the selected features. Later, Min-Max normalization was performed over the input feature vectors to alleviate any possibility of overfitting. Towards NoSQL-IA prediction, different machine learning methods like Multinomial Naïve Bayes, decision tree, logistic regression, support vector machine, k-NN, AdaBoost, Extra Tree Classifier, random forest ensemble, and XG-Boost were applied, which classified each input query as the regular query or the NoSQL-IA attack query. The depth performance assessment revealed that the use of Word2Vec features SKG in sync with VTFS feature selection and SMOTE resampling processed with the bootstrapped random forest classifier can provide the best performance in terms of high accuracy (98.86%), F-Measure (0.974), and area under the curve (AUC) (0.981), thus enabling it suitable for interoperable e-Healthcare database security.

Study of 2D Feature Extraction Techniques for Classification of Spinocerebellar Ataxia Type 12 (SCA12).

Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative genetic disorder triggered by abnormal CAG repeat expansion at locus 5q32. MRI recognises dissimilarities in affected areas of SCA12 patients and healthy subjects. But manual diagnosis is time-consuming and prone to subjective errors. This has motivated us in developing a systematic and authentic decision model for computer-aided diagnosis (CAD) of SCA12. Four different feature extraction techniques are examined in this research work, such as First Order Statistics, GLRLM, GLCM, and GLGCM, to obtain distinguishable characteristics for differentiating SCA12 patients from healthy subjects. The model's performance is measured using sensitivity, specificity, accuracy and F1-score with leave-one-out cross-validation scheme. Our experimental results show that features based on the GLRLM can distinguish SCA12 from healthy subjects with a maximum classification accuracy of 85% among all the different function extraction techniques used.

Impact of Tafamidis on Survival in a Real-World Community-Based Cohort.

Tafamidis is the only therapy shown to improve survival in transthyretin cardiac amyloidosis (ATTR) based on randomized controlled trial data. We sought to evaluate the impact of tafamidis on survival in a real-world community-based cohort. This was a prospective observational cohort study that included consecutive patients with confirmed ATTR based on biopsy or TcPYP imaging. Baseline characteristics were compared between patients taking tafamidis vs not, and Kaplan-Meier survival analysis was performed to compare survival between these groups. We examined the reasons that ATTR patients were not on tafamidis. Of 107 ATTR patients, median age was 83.9 years, 79% were men, and 63 (59%) of them were on tafamidis. Demographics and baseline cardiovascular risk factors did not differ significantly between those on vs off tafamidis, although there was a higher proportion of NYHA Class III or IV heart failure in those off tafamidis (76% vs 57%, P < 0.01). The most common reasons patients were not on tafamidis included delays in obtaining the drug or financial barriers (59%) and NYHA Class IV heart failure (19.5%). Patients taking tafamidis had a significantly higher median survival compared to those not on tafamidis (median survival 6.70 vs 1.43 years, P < 0.0001). Our study demonstrates significantly improved survival in ATTR patients taking tafamidis. Barriers exist to tafamidis initiation including delayed access and affordability, and efforts should be made to improve patient access.