Altered DTI scalars in the hippocampus are associated with morphological and structural changes after traumatic brain injury.

Blunt and diffuse injury is a highly prevalent form of traumatic brain injury (TBI) which can result in microstructural alterations in the brain. The blunt impact on the brain can affect the immediate contact region but can also affect the vulnerable regions like hippocampus, leading to functional impairment and long-lasting cognitive deficits. The hippocampus of the moderate weight drop injured male rats was longitudinally assessed for microstructural changes using in vivo MR imaging from 4 h to Day 30 post-injury (PI). The DTI analysis found a prominent decline in the apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) values after injury. The perturbed DTI scalars accompanied histological changes in the hippocampus, wherein both the microglia and astrocytes showed changes in the morphometric parameters at all timepoints. Along with this, the hippocampus showed presence of Aß positive fibrils and neurite plaques after injury. Therefore, this study concludes that TBI can lead to a complex morphological, cellular, and structural alteration in the hippocampus which can be diagnosed using in vivo MR imaging techniques to prevent long-term functional deficits.

Cortical Gray Matter Thickness and Volume Changes and Their Association with Memory Functions in Hyperthyroid Patients.

INTRODUCTION: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects. METHODS: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively. RESULTS: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness. CONCLUSION: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism.

Metabolomics and transcriptomics based multi-omics integration reveals radiation-induced altered pathway networking and underlying mechanism.

Recent advancement in integrated multi-omics has significantly contributed to many areas of the biomedical field. Radiation research has also grasped uprising omics technologies in biomarker identification to aid in triage management. Herein, we have used a combinatorial multi-omics approach based on transcriptomics together with metabolomics and lipidomics of blood from murine exposed to 1 Gy (LD) and 7.5 Gy (HD) of total-body irradiation (TBI) for a comprehensive understanding of biological processes through integrated pathways and networking. Both omics displayed demarcation of HD group from controls using multivariate analysis. Dysregulated amino acids, various PC, PE and carnitine were observed along with many dysregulated genes (Nos2, Hmgcs2, Oxct2a, etc.). Joint-Pathway Analysis and STITCH interaction showed radiation exposure resulted in changes in amino acid, carbohydrate, lipid, nucleotide, and fatty acid metabolism. Elicited immune response was also observed by Gene Ontology. BioPAN has predicted Elovl5, Elovl6 and Fads2 for fatty acid pathways, only in HD group. Collectively, the combined omics approach facilitated a better understanding of processes uncovering metabolic pathways. Presumably, this is the first in radiation metabolomics that utilized an integrated omics approach following TBI in mice. Our work showed that omics integration could be a valuable tool for better comprehending the mechanism as well as molecular interactions.

Systematic untargeted UHPLC-Q-TOF-MS based lipidomics workflow for improved detection and annotation of lipid sub-classes in serum.

INTRODUCTION AND OBJECTIVE: Taking into consideration the challenges of lipid analytics, present study aims to design the best high-throughput workflow for detection and annotation of lipids. MATERIAL AND METHODS: Serum lipid profiling was performed on CSH-C18 and EVO-C18 columns using UHPLC Q-TOF-MS and generated lipid features were annotated based on m/z and fragment ion using different software. RESULT AND DISCUSSION: Better detection of features was observed in CSH-C18 than EVO-C18 with enhanced resolution except for Glycerolipids (triacylglycerols) and Sphingolipids (sphingomyelin). CONCLUSION: The study revealed an optimized untargeted Lipidomics-workflow with comprehensive lipid profiling (CSH-C18 column) and confirmatory annotation (LipidBlast).

Acute metabolic alterations in the hippocampus are associated with decreased acetylation after blast induced TBI.

INTRODUCTION: Blast induced Traumatic brain injury (BI-TBI) is common among military personnels as well as war affected civilians. In the war zone, people can also encounter repeated exposure of blast wave, which may affect their cognition and metabolic alterations. OBJECTIVE: In this study we assess the metabolic and histological changes in the hippocampus of rats at 24 h post injury. METHOD: Rats were divided into four groups: (i) Sham; (ii) Mild TBI (mi); (iii) Moderate TBI (mo); and (iv) Repetitive mild TBI (rm TBI) and then subjected to different intensities of blast exposure. Hippocampal tissues were collected after 24 h of injury for proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) and immunohistochemical (IHC) analysis. RESULTS: The metabolic alterations were found in the hippocampal tissue samples and these alterations showed significant change in glutamate, N-Acetylaspartic acid (NAA), acetate, creatine, phosphoethanolamine (PE), ethanolamine and PC/choline concentrations in rmTBI rats only. IHC studies revealed that AH3 (Acetyl histone) positive cells were decreased in rm TBI tissue samples in comparison to other TBI groups and sham rats. This might reflect an epigenetic alteration due to repeated blast exposure at 24 h post injury. Additionally, astrogliosis was observed in miTBI and moTBI hippocampal tissue while no change was observed in rmTBI tissues. CONCLUSION: The present study reports altered acetylation in the presence of altered metabolism in hippocampal tissue of blast induced rmTBI at 24 h post injury. Mechanistic understanding of these intertwined processes may help in the development of better therapeutic pathways and agents for blast induced TBI in near future.

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India.

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.

An integrative chemometric approach and correlative metabolite networking of LC-MS and 1H NMR based urine metabolomics for radiation signatures.

The increasing threat of nuclear terrorism or radiological accident has made high throughput radiation biodosimetry a requisite for the immediate response for triage. Owing to detection of subtle alterations in biological pathways before the onset of clinical conditions, metabolomics has become an important tool for studying biomarkers and the related mechanisms for radiation induced damage. Here, we have attempted to combine two detection techniques, LC-MS and 1H NMR spectroscopy, to obtain a comprehensive metabolite profile of urine at 24 h following lethal (7.5 Gy) and sub-lethal (5 Gy) irradiation in mice. Integrated data analytics using multiblock-OPLSDA (MB-OPLSDA), correlation networking and pathway analysis was used to identify metabolic disturbances associated with radiation exposure. MB-OPLSDA revealed better clustering and separation of irradiated groups compared with controls without overfitting (p-value of CV-ANOVA: 1.5 × 10-3). Metabolites identified through MB-OPLSDA, namely, taurine, creatine, citrate and 2-oxoglutarate, were found to be dose independent markers and further support and validate our earlier findings as potential radiation injury biomarkers. Integrated analysis resulted in the enhanced coverage of metabolites and better correlation networking in energy, taurine, gut flora, L-carnitine and nucleotide metabolism observed post irradiation in urine. Our study thus emphasizes the major advantage of using the two detection techniques along with integrated analysis for better detection and comprehensive understanding of disturbed metabolites in biological pathways.

Brain functional connectivity in patients with hyperthyroidism after anti-thyroid treatment.

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

Neurometabolite Changes in Hyperthyroid Patients Before and After Antithyroid Treatment: An in vivo 1H MRS Study.

Purpose: Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (1H MRS). Materials and Methods: We collected neuropsychological and 1H MRS data from posterior parietal cortex and DLPFC, in both control (N = 30) and hyperthyroid (N = 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired t-test was applied in patients at baseline and follow-up. Spearman's rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment. Results: Our results revealed a significant decrease in choline/creatine [glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr)] in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (N-acetyl aspartate + N-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment. Conclusion: The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.

A Novel Deep Learning-based Whale Optimization Algorithm for Prediction of Breast Cancer

HIGHLIGHTS Novel whale optimization algorithm is proposed for prediction of breast cancer. Deep learning-based WOA adjusts the CNN structure as per maximum detection accuracy. Proposed method achieves 92.4% accuracy in comparison to 90.3%. Validity of method is evaluated with magnifying factors like 40x, 100 x, 200x, 400x.

Abstract Breast cancer is one of the most common cancers among women that cause billions of deaths worldwide. Identification of breast cancer often depends on the examination of digital biomedical photography such as the histopathological images of various health professionals, and clinicians. Analyzing histopathological images is a unique task and always requires special knowledge to conclude investigating these types of images. In this paper, a novel efficient technique has been proposed for the detection and prediction of breast cancer at its early stage. Initially, the dataset of images is used to carry out the pre-processing phase, which helps to transform a human pictorial image into a computer photographic image and adjust the parameters appropriate to the Convolutional neural network (CNN) classifier. Afterward, all the transformed images are assigned to the CNN classifier for the training process. CNN classifies incoming breast cancer clinical images as malignant and benign without prior information about the occurrence of cancer. For parameter optimization of CNN, a deep learning-based whale optimization algorithm (WOA) has been proposed which proficiently and automatically adjusts the CNN network structure by maximizing the detection accuracy. We have also compared the obtained accuracy of the proposed algorithm with a standard CNN and other existing classifiers and it is found that the proposed algorithm supersedes the other existing algorithms.

Comparative metabolic profiles of total and partial body radiation exposure in mice using an untargeted metabolomics approach.

INTRODUCTION: A large scale population exposure to ionizing radiation during intentional or unintentional nuclear accidents undoubtedly generates a complex scenario with partial-body as well as total-body irradiated victims. A high throughput technique based rapid assessment method is an urgent necessity for stratification of exposed subjects independent of whether exposure is uniform total-body or non-homogenous partial-body. OBJECTIVE: Here, we used Nuclear Magnetic Resonance (NMR) based metabolomics approach to compare and identify candidate metabolites differentially expressed in total and partially irradiated mice model. METHODS: C57BL/6 male mice (8-10 weeks) were irradiated total-body or locally to thoracic, hind limb or abdominal regions with 10 Gy of gamma radiation. Urine samples collected at 24 h post irradiation were examined using high resolution NMR spectroscopy and the datasets were analysed using multivariate analysis. RESULTS: Multivariate and metabolic pathway analysis in urine samples collected at 24 h post-radiation exhibited segregation of all irradiated groups from controls. Metabolites associated with energy metabolism, gut flora metabolism and taurine were common to partial and total-body irradiation, thus making them potential candidates for radiation exposure. Nevertheless, a distinct metabolic pattern was observed in partial-body exposed groups with maximum changes observed in the hind limb region indicating differential tissue associated radiation sensitivity. The organ-specific changes may provide an early warning regarding the physiological system at risk after radiation injury. CONCLUSION: The study affirms potentiality of metabolite markers and comparative analysis could be an important piece of information for an integrated solution to a complex research question in terms of radiation biomarkers.

Urine metabolomics based prediction model approach for radiation exposure.

The radiological incidents and terrorism have demanded the need for the development of rapid, precise, and non-invasive technique for detection and quantification of exposed dose of radiation. Though radiation induced metabolic markers have been thoroughly investigated, but reproducibility still needs to be elucidated. The present study aims at assessing the reliability and reproducibility of markers using nuclear magnetic resonance (NMR) spectroscopy and further deriving a logistic regression model based on these markers. C57BL/6 male mice (8-10 weeks) whole body γ-irradiated and sham irradiated controls were used. Urine samples collected at 24 h post dose were investigated using high resolution NMR spectroscopy and the datasets were analyzed using multivariate analysis. Fifteen distinguishable metabolites and 3 metabolic pathways (TCA cycle, taurine and hypotaurine metabolism, primary bile acid biosynthesis) were found to be amended. ROC curve and logistic regression was used to establish a diagnostic model as Logit (p) = log (p/1 - p) = -0.498 + 13.771 (tau) - 3.412 (citrate) - 34.461 (α-KG) + 515.183 (fumarate) with a sensitivity and specificity of 1.00 and 0.964 respectively. The findings demonstrate the proof of concept and the potential of NMR based metabolomics to establish a prediction model that can be implemented as a promising mass screening tool during triage.

Oxidative stress contributes to cerebral metabolomic profile changes in animal model of blast-induced traumatic brain injury.

INTRODUCTION: Blast-induced neurotrauma (BINT) has been recognized as the common mode of traumatic brain injury amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from this laboratory have identified three major pathological events following BINT which include blood brain barrier disruption the earliest event, followed by oxidative stress and neuroinflammation as secondary events occurring a few hours following blast. OBJECTIVES: Our recent studies have also identified an increase in oxidative stress mediated by the activation of superoxide producing enzyme NADPH oxidase (NOX) in different brain regions at varying levels with neurons displaying higher oxidative stress (NOX activation) compared to any other neural cell. Since neurons have higher energy demands in brain and are more prone to oxidative damage, this study evaluated the effect of oxidative stress on blast-blast induced changes in metabolomics profiles in different brain regions. METHODS: Animals were exposed to mild/moderate blast injury (180 kPa) and examined the metabolites of energy metabolism, amino acid metabolism as well as the profiles of plasma membrane metabolites in different brain regions at different time points (24 h, 3 day and 7 day) after blast using 1H NMR spectroscopy. Effect of apocynin, an inhibitor of superoxide producing enzyme NADPH oxidase on cerebral metabalomics profiles was also examined. RESULTS: Several metabolomic profile changes were observed in frontal cortex and hippocampus with concomitant decrease in energy metabolism. In addition, glutamate/glutamine and other amino acid metabolism as well as metabolites involved in plasma membrane integrity were also altered. Hippocampus appears metabolically more vulnerable than the frontal cortex. A post-treatment of animals with apocynin, an inhibitor of NOX activation significantly prevented the changes in metabolite profiles. CONCLUSION: Together these studies indicate that blast injury reduces both cerebral energy and neurotransmitter amino acid metabolism and that oxidative stress contributes to these processes. Thus, strategies aimed at reducing oxidative stress can have a therapeutic benefit in mitigating metabolic changes following BINT.

Alterations of connectivity patterns in functional brain networks in patients with mild traumatic brain injury: A longitudinal resting-state functional magnetic resonance imaging study.

AIM: In the present study, we aimed to characterise changes in functional brain networks in individuals who had sustained uncomplicated mild traumatic brain injury (mTBI). We assessed the progression of these changes into the chronic phase. We also attempted to explore how these changes influenced the severity of post-concussion symptoms as well as the cognitive profile of the patients. METHODS: A total of 65 patients were prospectively recruited for an advanced magnetic resonance imaging (MRI) scan within 7 days of sustaining mTBI. Of these, 25 were reassessed at 6 months post injury. Differences in functional brain networks were analysed between cases and age- and sex-matched healthy controls using independent component analysis of resting-state functional MRI. RESULTS: Our study revealed reduced functional connectivity in multiple networks, including the anterior default mode network, central executive network, somato-motor and auditory network in patients who had sustained mTBI. A negative correlation between network connectivity and severity of post-concussive symptoms was observed. Follow-up studies performed 6 months after injury revealed an increase in network connectivity, along with an improvement in the severity of post-concussion symptoms. Neurocognitive tests performed at this time point revealed a positive correlation between the functional connectivity and the test scores, along with a persistence of negative correlation between network connectivity and post-concussive symptom severity. CONCLUSION: Our results suggest that uncomplicated mTBI is associated with specific abnormalities in functional brain networks that evolve over time and may contribute to the severity of post-concussive symptoms and cognitive deficits.

Aberrant intra and inter network resting state functional connectivity in thyrotoxicosis.

Thyroid hormones epigenetically play an important role in the regularisation of neural networks and in neural differentiation during brain development. The present study aimed to explore the intra and inter network resting state functional connectivity changes underlying the neurobehavioural symptoms in thyrotoxicosis. To understand the pathophysiological changes, we investigated the correlation between functional connectivity and clinical and behavioural measures. Twenty-eight freshly diagnosed thyrotoxicosis patients suffering with symptoms such as palpitation, loss of weight, trembling and heat intolerance from days to weeks and 28 healthy controls were recruited for the study. Thyrotoxicosis patients showed significantly decreased functional connectivity in sensorimotor network, fronto-temporal network, default mode network, right fronto-parietal network, left fronto-parietal network and salience network. Inter network functional connectivity was significantly reduced between the basal ganglia network and sensorimotor network and increased between the salience network and fronto-temporal network in thyrotoxicosis. Cognitive functions such as visual retention, recognition of objects, mental balance and performance on neuropsychological tests (ie, the Bender Gestalt test, Nahar-Benson test and Mini Mental State Examination) also showed significant decline in thyrotoxicosis patients. The altered intrinsic resting state functional connectivity might underlie these cognitive deficits. The increased functional connectivity between the salience network and fronto-temporal network suggests the recruitment of additional neuronal circuitry needed to compensate for the neuropathology in the primary neural network in thyrotoxicosis.

Trichostatin A, an epigenetic modifier, mitigates radiation-induced androphysiological anomalies and metabolite changes in mice as evident from NMR-based metabolomics.

PURPOSE: Ionizing radiation is known to damage male reproductive system. Current study aims to study the mitigative effects of trichostatin A on male reproductive system and accompanying metabolite changes in testicular tissue of mice. MATERIALS AND METHODS: Eight-week-old male C57 Bl/6J mice were exposed to 2 Gy γ-radiation with or without trichostatin A administration. The animals were sacrificed at various time intervals for organ body weight index, sperm head abnormality assay, sperm mobility assay, and study of various metabolites in testicular tissue using NMR spectroscopy. RESULTS: Ionizing radiation induced no significant change in organ body weight index at any time points studied, however a significant increase in sperm head abnormality and significant decrease in sperm mobility was evident on fifth postirradiation week. trichostatin A administration, 1 and 24 h postirradiation, could efficiently mitigate radiation-induced changes studied. NMR metabolome profile also showed prominent changes associated with energy metabolism, osmolytes and membrane metabolism at 24 h postirradiation and some of these changes (choline, glycerolphosphoethanol amine, and glycine) were persistent till fifth postirradiation week. Trichostatin A administration resulted in reverting metabolic profile of the irradiated animals to normal level suggesting its mitigative role. CONCLUSION: Results obtained suggest that trichostatin A could restore normal metabolic profile of testicular tissue of irradiated male mice and also restored certain morphological and functional properties of sperms. Trichostatin A thus could further be exploited for its radio-mitigative properties.

Knowledge, attitude, and practice among tobacco and alcohol addicts before and after psychological intervention in a de-addiction center at Madhya Pradesh, India.

CONTEXT: Tobacco and alcohol addiction has emerged as a major public health issue in most of the regions of the world. It has resulted in enormous disability, disease, and death and acquired the dimension of an epidemic. It is estimated that five million preventable deaths occur every year globally, attributable to tobacco use. The number is expected to double by 2020 if death due to tobacco continues to occur at the same rate. Alcohol, on the other hand, contributes to 25% of all deaths in the age group of 20-39 years. The interventions such as supportive pharmacotherapy, nicotine replacement therapy, counseling, behavioral intervention, psychotherapy, and detoxification therapy are being commonly employed in the management of patients with addiction to tobacco and alcohol. AIM: The aim of this study is to compare the knowledge, attitude, and practice (KAP) among tobacco and alcohol addicts before and after psychological intervention in a de-addiction center. SETTINGS AND DESIGN: This study was a randomized control trial, focusing on psychological interventions practiced in a de-addiction center, Indore, Madhya Pradesh, India. MATERIALS AND METHODS: The information on KAP related to tobacco and alcohol was collected at baseline from 83 participants. This was compared with the information collected in the postintervention follow-ups from each participant. STATISTICAL ANALYSIS USED: Statistical tests for parametric analysis were done using one-way ANOVA with Scheffe's post hoc test, RMANOVA with Mauchly's test for sphericity assumption, and Bonferroni test for comparing the main effects. Nonparametric tests included Pearson's Chi-square test, McNemar's Chi-square test, Spearman's rho, and Kruskal-Wallis test. The statistical significance was fixed at 0.05. RESULTS: The mean KAP score for the study population was highest at the first follow-up followed by the second follow-up for both tobacco and alcohol addiction. The least KAP score was observed at the baseline. CONCLUSIONS: Although a significant improvement in the mean KAP score was observed at the first follow-up, subsequent follow-up revealed a reduction in the overall KAP score in the present study. This could be attributed to the fact that following their discharge from the de-addiction center, most of the participants reverted back to their deleterious habits.

Longitudinal changes in gray matter regions after cranial radiation and comparative analysis with whole body radiation: a DTI study.

PURPOSE: Radiation-induced white matter changes are well known and vastly studied. However, radiation-induced gray matter alterations are still a research question. In the present study, these changes were assessed in a longitudinal manner using Diffusion Tensor Imaging (DTI) and further compared for cranial and whole body radiation exposure. MATERIALS AND METHODS: Male mice (C57BL/6) were irradiated with cranial or whole body radiation followed by DTI study at 7T animal MRI system during predose, subacute and early delayed phases of radiation sickness. Fractional anisotropy (FA) and mean diffusivity (MD) values were obtained from brain's gray matter regions. RESULTS: Decreased FA with increased MD was observed prominently in animals exposed to cranial radiation showing most changes at 8 months post irradiation. However, whole body radiation induced FA changes were mostly observed at 1 month post irradiation as compared to controls. CONCLUSIONS: The differential response after whole body and cranial irradiation observed in the study depicts that radiation exposure of 5 Gy could induce permanent alterations in gray matter regions prominently as observed in Caudoputamen region at all the time points. Thus, our study has bolstered the role of DTI to probe microstructural changes in gray matter regions of brain after radiation exposure.

Alteration in intrinsic and extrinsic functional connectivity of resting state networks associated with subclinical hypothyroid.

Subclinical hypothyroidism (SCH) is characterized by mild elevation of thyroid stimulating hormone (TSH) (range 5-10 µIU/ml) and normal free triiodothyronine (FT3) and free thyroxine (FT4). The cognitive function impairment is well known in thyroid disorders such as hypothyroidism and hyperthyroidism, but little is known about deficits in brain functions in SCH subjects. Also, whether hormone-replacement treatment is necessary or not in SCH subjects is still debatable. In order to have an insight into the cognition of SCH subjects, intrinsic and extrinsic functional connectivity (FC) of the resting state networks (RSNs) was studied. For resting state data analysis we used an unbiased, data-driven approach based on Independent Component Analysis (ICA) and dual-regression that can emphasize widespread changes in FC without restricting to a set of predefined seeds. 28 SCH subjects and 28 matched healthy controls (HC) participated in the study. RSN analysis showed significantly decreased intrinsic FC in somato-motor network (SMN) and right fronto-parietal attention network (RAN) and increased intrinsic FC in default mode network (DMN) in SCH subjects as compared to control subjects. The reduced intrinsic FC in the SMN and RAN suggests neuro-cognitive alterations in SCH subjects in the corresponding functions which were also evident from the deficit in the neuropsychological performance of the SCH subjects on behavioural tests such as digit span, delayed recall, visual retention, recognition, Bender Gestalt and Mini-Mental State Examination (MMSE). We also found a significant reduction in extrinsic network FC between DMN and RAN; SMN and posterior default mode network (PDMN); and increased extrinsic FC between SMN and anterior default mode network (ADMN) in SCH subjects as compared to controls. An altered extrinsic FC in SCH suggests functional reorganization in response to neurological disruption. The partial correlation analysis between intrinsic and extrinsic RSNs FC and neuropsychological performances as well as clinical indices give interesting insights into brain-behavior relationship in SCH subjects. This article is protected by copyright. All rights reserved.

Effectiveness of two psychological intervention techniques for de-addiction among patients with addiction to tobacco and alcohol - A double-blind randomized control trial.

OBJECTIVE: The objective of this study was to evaluate effectiveness of two psychological intervention techniques (reading - writing therapy vs. games - narrative therapy) using motivational intervention alone as a control among tobacco addicts. MATERIALS AND METHOD: This randomized control trial was conducted over a period of 6 months from April to September 2013 at a de-addiction center in Madhya Pradesh, India. Patients with moderate-to-high levels of dependence as determined by Fagerstrom Test for Nicotine Dependence (FTND) admitted for treatment in a de-addiction center were recruited. A cluster randomization technique was used for allocation of participants to three different groups. Group allocation was concealed from investigator and done by coordinator. Three interventions were group A - motivational intervention alone, group B - games and story therapy along with motivational intervention, and group C - reading and writing therapy along with motivational intervention. Interventions were applied for 1 month. Two postintervention follow-ups (one at the time of discharge and one after 1 month following discharge) were done to assess level of dependence using FTND besides undertaking urine cotinine analysis among three randomly selected participants in each group. RESULTS: A total of 82 participants (28 in group A, 27 each in groups B and C) completed the study. Eighty-one (98.8%) participants had complete abstinence at the end of 1 month with no significant difference in the success rate between different categories (P = 0.357). At the end of 1 month following discharge from center, only 7 participants (8.5%) had complete abstinence and 51 participants (62.2%) had partial reduction and remaining 24 participants (29.3%) were considered failures with no difference between three groups (P = 0.768). CONCLUSION: Although overall abstinence was low (8.5%), all intervention techniques were equally effective in at least reducing level of dependence with no significant difference in their efficacy.