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.

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.

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.

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.

Early detection of whole body radiation induced microstructural and neuroinflammatory changes in hippocampus: A diffusion tensor imaging and gene expression study.

Ionizing radiation is known to a cause systemic inflammatory response within hours of exposure that may affect the central nervous system (CNS). The present study was carried out to look upon the influence of radiation induced systemic inflammatory response in hippocampus within 24 hr of whole body radiation exposure. A Diffusion Tensor Imaging (DTI) study was conducted in mice exposed to a 5-Gy radiation dose through a 60 Co source operating at 2.496 Gy/min at 3 hr and 24 hr post irradiation and in sham-irradiated controls using 7 T animal MRI system. The results showed a significant decrease in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AD) in hippocampus at 24 hr compared with controls. Additionally, marked change in RD was observed at 3 hr. Increased serum C-Reactive Protein (CRP) level depicted an increased systemic/peripheral inflammation. The neuroinflammatory response in hippocampus was characterized by increased mRNA expression of IL-1ß, IL-6, and Cox-2 at the 24 hr time point. Additionally, in the irradiated group, reactive astrogliosis was illustrated, with noticeable changes in GFAP expression at 24 hr. Altered diffusivity and enhanced neuroinflammatory expression in the hippocampal region showed peripheral inflammation induced changes in brain. Moreover, a negative correlation between gene expression and DTI parameters depicted a neuroinflammation induced altered microenvironment that might affect water diffusivity. The study showed that there was an influence of whole body radiation exposure on hippocampus even during the early acute phase that could be reflected in terms of neuroinflammatory response as well as microstructural changes. © 2016 Wiley Periodicals, Inc.

Altered metabolites of the rat hippocampus after mild and moderate traumatic brain injury - a combined in vivo and in vitro 1 H-MRS study.

Traumatic brain injury (TBI) has been shown to affect hippocampus-associated learning, memory and higher cognitive functions, which may be a consequence of metabolic alterations. Hippocampus-associated disorders may vary depending on the severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since injury. The underlying hippocampal metabolic irregularities may provide an insight into the pathological process following TBI. In this study, in vivo and in vitro proton magnetic resonance spectroscopy (1 H-MRS) data were acquired from the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre-injury), 4 h, Day 1 and Day 5 post-injury (PI). In vitro MRS results indicated trauma-induced changes in both miTBI and moTBI; however, in vivo MRS showed metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of osmolytes indicating injury-induced edema. Altered levels of citric acid cycle intermediates, glutamine/glutamate and amino acid metabolism indicated injury-induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall similar pattern of pathological process was observed in both miTBI and moTBI, with the distinction of depleted N-acetylaspartate levels (indicating neuronal loss) at 4 h and Day 1 and enhanced lactate production (indicating heightened energy depletion leading to the commencement of the anaerobic pathway) at Day 5 in moTBI. To the best of our knowledge, this is the first study to investigate the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo and in vitro MRS.

Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism.

Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1ß (IL-1ß) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity.

Effect of vitamin D supplementation on muscle energy phospho-metabolites: a ³¹P magnetic resonance spectroscopy-based pilot study.

There are several published reports on the prevalence of low vitamin D levels in otherwise healthy Indian population. Vitamin D deficiency has shown variable effect on muscle performance and strength but there is paucity of data on the effect of vitamin D deficiency on muscle energy metabolism. The present study was proposed to investigate the influence of severe vitamin D deficiency on high-energy metabolite levels in resting skeletal muscle and thereafter, monitor the response after vitamin D supplementation using ³¹P magnetic resonance spectroscopy (MRS). Study was conducted on 19 otherwise healthy subjects but with low serum 25(OH)D levels (<5 ng/ml). Subjects were supplemented with cholecalciferol at a dose of 60,000 IU/week for 12 weeks. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiester (PDE) and ATP of the calf muscle were taken pre- and post-vitamin D supplementation. The study revealed significantly increased PCr/Pi ratio and decreased [Pi] and PDE/ATP ratio with raised serum 25(OH)D levels after 12 weeks of supplementation. The study indicates that serum 25(OH)D level plays an important role in improving the skeletal muscle energy metabolism and vitamin D deficiency might be one of the primary reasons for prevalence of low PCr/Pi ratio and high PDE values in normal Indian population as reported earlier. The findings of this preliminary study are highly encouraging and warrant further in-depth research, involving larger number of subjects of different age groups, regions and socio-economic sections of the society to further strengthen a correlation between vitamin D levels and muscle energy metabolism.

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.

Lipidomic Analysis Reveals Systemic Alterations in Servicemen Exposed to Repeated Occupational Low-Level Blast Waves.

INTRODUCTION: Occupational exposure to blast is a prevalent risk experienced by military personnel. While low-level exposure may not manifest immediate signs of illness, prolonged and repetitive exposure may result in neurophysiological dysfunction. Such repeated exposure to occupational blasts has been linked to structural and functional modifications in the brain, adversely affecting the performance of servicemen in the field. These neurological changes can give rise to symptoms resembling concussion and contribute to the development of post-traumatic stress disorder. MATERIALS AND METHODS: To understand long-term effects of blast exposure, the study was conducted to assess memory function, serum circulatory protein and lipid biomarkers, and associated concussive symptomology in servicemen. Concussion-like symptoms were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ) along with memory function using PGI memory scale. The serum protein biomarkers were quantified using a sandwich ELISA assay, and the serum lipid profile was measured using liquid chromatography-mass spectrometer. RESULTS: The findings revealed that repeated low-level blast exposure resulted in impaired memory function, accompanied by elevated levels of serum neurofilament light chain (neuroaxonal injury) and C-reactive protein. Furthermore, alterations in the lipid profile were observed, with an increase in lipid species associated with immune activation. These changes collectively point to systemic inflammation, neuronal injury, and memory dysfunction as pathological characteristics of repeated low-level blast exposure. CONCLUSION: The results of our preliminary investigation offer valuable insights for further large-scale study and provide a guiding principle that necessitates a suitable mitigation approach to safeguard the health of personnel against blast overpressure.

Comparative evaluation of brain neurometabolites and DTI indices following whole body and cranial irradiation: a magnetic resonance imaging and spectroscopy study.

Understanding early differential response of brain during whole body radiation or cranial radiation exposure is of significant importance for better injury management during accidental or intentional exposure to ionizing radiation. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H MRS) following whole body and cranial radiation exposure of 8 Gy in mice using a 7.0 T animal MRI system and compared profiles with sham controls at days 1, 3, 5 and 10 post irradiation. A significant decrease in fractional anisotropy (FA) values was found in hippocampus, thalamic and hypothalamic regions (p < 0.05) in both whole body and cranial irradiated groups compared with controls, suggesting radiation induced reactive astrogliosis or neuroinflammatory response. In animals exposed to whole body radiation, FA was significantly decreased in some additional brain regions such as sensory motor cortex and corpus callosum in comparison with cranial irradiation groups and controls. Changes in FA were observed till day 10 post irradiation in both the groups. However, MRS study from hippocampus revealed changes only in the whole body radiation dose group. Significant reduction in the ratios of the metabolites myoinositol (mI, p = 0.02) and taurine (tau, p = 0.03) to total creatine were observed, and these metabolic alterations persisted till day 10 post irradiation. To the best of our knowledge this study has for the first time documented a comparative account of microstructural and metabolic aspects of whole body and cranial radiation induced early brain injury using in vivo MRI. Overall our findings suggest differential response at microstructure and metabolite levels following cranial or whole body radiation exposure.

Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy.

Heavy metals are known for their associated nephrotoxicity and nickel is no exception. An integrated metabonomic approach, based on high-resolution (1) H NMR spectroscopy, was applied to determine the acute biochemical effects of NiCl(2) on the renal tissues of rats. Kidney homogenates from rats treated with NiCl(2) at two dose levels (4 and 20 mg kg(-1) b.w., i.p.) and those from controls were analysed using (1) H NMR spectroscopy and also assessed for antioxidant parameters at days 1, 3 and 5 post-dose. The major metabolite changes corresponding to nickel exposure were related to amino acids, osmolytes and energy metabolites. Differential responses were observed in (1) H NMR spectra with exposure to low and high doses of NiCl(2). For high doses, (1) H NMR spectral analysis revealed alterations in renal tissues, along with damage to the cortical and papillary region and depletion of renal osmolytes such as betaine, trimethyl amine oxide, myo-inositol and taurine, which persisted until day 5 post-dose. The metabolite profile of (1) H NMR spectra obtained from animals treated with lower dose of NiCl(2) initially increased as an immediate stress response and then showed signs of recovery with the passage of time. NMR spectral analysis was well corroborated with histopathological and oxidative stress results. Nickel-induced oxidative stress was observed in both groups of animals with increased levels of antioxidant parameters at initial time points, but continued to increase in the high-dose group. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal toxicity.

Ectopic pregnancy: a review.

PURPOSE: Ectopic pregnancy (EP) presents a major health problem for women of child-bearing age. EP refers to the pregnancy occurring outside the uterine cavity that constitutes 1.2-1.4 % of all reported pregnancies. All identified risk factors are maternal: pelvic inflammatory disease, Chlamydia trachomatis infection, smoking, tubal surgery, induced conception cycle, and endometriosis. These developments have provided the atmosphere for trials using methotrexate as a non-surgical treatment for EP. The diagnosis measure of EP is serum human chorionic gonadotropin, urinary hCGRP/i-hCG, progesterone measurement, transvaginal ultrasound scan, computed tomography, vascular endothelial growth factor, CK, disintegrin and metalloprotease-12 and hysterosalpingography. The treatment option of EP involves surgical treatment by laparotomy or laparoscopy, medical treatment is usually systemic or through local route, or by expectant treatment. RESULTS: It was concluded that review data reflect a decrease in surgical treatment and not an actual decline in EP occurrence so that further new avenues are needed to explore early detection of the EP.

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.

Radiation-induced early changes in the brain and behavior: serial diffusion tensor imaging and behavioral evaluation after graded doses of radiation.

The nuclear arsenal and the use of nuclear technologies have enhanced the likelihood of whole-body/partial-body radiation exposure. The central nervous system is highly susceptible to even low doses of radiation. With the aim of detecting and monitoring the pathologic changes of radiation-induced damage in brain parenchyma, we used serial diffusion tensor magnetic resonance imaging (DTI) with a 7T magnetic resonance unit and neurobehavioral assessments mice irradiated with 3-, 5-, and 8-Gy doses of radiation. Fractional anisotropy (FA) and mean diffusivity (MD) values at each time point (baseline, day 1, day 5, and day 10) were quantified from hippocampus, thalamus, hypothalamus, cudate-putamen, frontal cortex, sensorimotor cortex, corpus callosum, cingulum, and cerebral peduncle. Behavioral tests were performed at baseline, day 5, and day 10. A decrease in FA values with time was observed in all three groups. At day 10, dose-dependent decreases in FA and MD values were observed in all of the regions compared with baseline. Behavioral data obtained in this study correlate with FA values. Radiation-induced affective disorders were not radiation dose dependent, insofar as the anxiety-like symptoms at the lower dose (3 Gy) mimics to the symptoms with the higher dose (8 Gy) level but not with the moderate dose. However, there was a dose-dependent decline in cognitive function as well as FA values. Behavioral data support the DTI indices, so it is suggested that DTI may be a useful tool for noninvasive monitoring of radiation-induced brain injury.

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.

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.

Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and ß-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity.