Hydrogen sulfide promotes migration of trophoblast cells by a Rho GTPase mediated actin cytoskeleton reorganization.

INTRODUCTION: Preeclampsia (PE) arises due to defective spiral artery remodelling which may be due to deficient migration of trophoblast cells. Migration of human endothelial cells has been shown to be promoted via Hydrogen sulphide(H2S)/Rho GTPase Rac1 axis. This novel role of H2S and its downstream processes have not yet been studied in the development and function of the placental trophoblast cells. METHODS: Placental tissues were obtained post-delivery from consented preeclamptic and normotensive mothers (n = 60). The protein expression levels of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) along with its downstream migratory molecules were compared in both the arms. The pro-migratory role of H2S was investigated in a first trimester placental cell line. RESULTS: H2S promoted the migration of trophoblast cells in a Rho GTPase dependent manner mediated by actin cytoskeleton reorganization. The reduced levels of H2S producing enzymes in the PE placentae along with decreased levels of Rho GTPases (Rac1 and Rho A) corroborate the results of PAG and AOAA treatment in down regulating the Rho GTPases in the in vitro grown placental cultures. Reduction of the migratory potential of trophoblastic cells caused due to hypoxia/reoxygenation was rescued by upregulating the H2S expression with the use of NaHS as a H2S donor. DISCUSSION: Exogenous H2S increases the migratory potential of the placental cells in culture conditions and also post hypoxia/reoxygenation injury. H2S as a gaso-transmitter holds a great potential as a therapeutic agent. Its long-term effects need to be investigated using model systems (rat/mouse) of PE following it up with clinical regulatory trials.

Citicoline in acute ischemic stroke: A randomized controlled trial.

INTRODUCTION: Two pharmacological possibilities exist for an acute ischemic stroke (AIS): recanalization of the occluded artery and neuroprotection from ischaemic injury, the latter's efficacy being debatable. We sought to determine whether administration of Citicoline immediately after recanalization therapy for AIS would improve clinical and radiological outcome at three months compared to standard treatment alone. PATIENTS AND METHODS: CAISR was a single centre, randomized, placebo-controlled, parallel-group trial with blinded endpoint assessment. It was approved by the All India Institute of Medical Sciences Institutional ethics committee and registered at the Clinical Trial Registry of India (CTRI/2018/011900). We recruited participants with AIS undergoing recanalization therapy and randomly assigned them to receive either Citicoline or placebo in 1:1 ratio. Citicoline arm patients received Citicoline 1gm BD intravenously for three days, followed by oral citicoline 1gm BD for 39 days. Placebo arm patients received 100ml intravenous normal saline for three days, followed by multivitamin tablet BD for 39 days. All patients received standard of care. OUTCOME: Blinded assessors did the follow-up assessment at six weeks (MRI Brain-stroke volume) and three months (NIHSS 0-2, mRS 0-2 and Barthel index> = 95). RESULTS: The infarct volume decreased from week 1 to week 6 by 2.6 cm3 on placebo versus 4.2 cm3 on Citicoline (p-0.483). The OR for achieving NIHSS 0-2, mRS 0-2 and Barthel index> = 95 with Citicoline was found to be 0.96(95%CI 0.39-2.40), 0.92(95%CI 0.40-2.05) and 0.87(95%CI 0.22-2.98) respectively. CONCLUSION: CAISR was the first to evaluate the role of Citicoline, when used immediately after recanalization therapy, when the penumbral tissue is the most susceptible either to be protected from injury or become ischemic. We did not find any significant difference between the Citicoline or placebo arms with respect to either our primary or secondary outcomes.

Blood Circulatory Level of Seven Sirtuins in Alzheimer's Disease: Potent Biomarker Based on Translational Research.

Alzheimer's disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuin (SIRT1-SIRT7) proteins in three study groups: AD, mild cognitive impairment (MCI) and geriatric control (GC) by surface plasmon resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3 and SIRT6 levels (mean ± SD) were significantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32 ng/µl), compared to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48 ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55 ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in the case of other SIRTs between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3 and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.

Circulatory GSK-3ß: Blood-Based Biomarker and Therapeutic Target for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3ß and p53 accounts for tau hyperphosphorylation and the formation of amyloid-ß plaques. OBJECTIVE: Here, we explored GSK-3ß and p53 as blood-based biomarkers for early detection of AD. METHODS: The levels of GSK-3ß, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. RESULTS: GSK-3ß, p53, and their phosphorylated states were significantly over expressed (p > 0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3ß and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. CONCLUSION: These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

Early Post-Stroke Seizures in Acute Ischemic Stroke: A Prospective Cohort Study.

INTRODUCTION: Stroke is the most common cause of epilepsy in the adult population. Post-stroke seizures (PSSs) are classified into early-onset seizures (ES) and late-onset (LS). ES can significantly affect the clinical outcome and occurrence of LS. METHODS: We analyzed data from a prospective cohort of acute ischemic stroke patients between June 2018 and May 2020 in a neurology unit at a tertiary hospital. We screened all acute stroke patients and included consecutive patients older than 18 years of age, presenting with acute, first-ever neuroimaging-confirmed ischemic stroke. We excluded patients with a previous stroke, transient ischemic attacks, hemorrhagic stroke, cerebral venous thrombosis, prior history of seizures, or any other epileptogenic comorbidity. ES were classified as spontaneous seizures occurring within 1 week of the stroke. The main outcome assessed was the occurrence of ES. The secondary outcome was to determine predictors of ES and create an ES prediction score. RESULTS: We screened 432 patients; of them, 291 were enrolled. ES occurred in 37 patients (12.7%). Cortical location (OR: 4.2), large artery disease subtype (OR: 2.9), mRS at presentation (OR: 1.4), use of anticoagulants (OR: 2.6), and hypertension (OR: 0.3) were significantly associated with the occurrence of ES. Patients with ES had a statistically significant worse clinical outcome at 3 months follow-up (P = 0.0072). CONCLUSION: We could formulate an ES prediction tool using the following components: (a) cortical location, (b) large vessel stroke, (c) mRS at admission, (d) anticoagulant use, and (e) presence of hypertension. This tool might help in treating patients at high risk for ES with prophylactic ASD, thereby preventing seizures and their complications.

Lung cancer in the older population:Interactive effects of angiotensin converting enzyme gene polymorphism (rs 4340 ID) and tobacco addiction in risk assessment.

BACKGROUND: rs4340ID polymorphism of angiotensin-converting enzyme (ACE) correlates with serum ACE levels in many known cancers. This study analyzed ACE rs4340 ID polymorphism in lung cancer (LC) in older patients of North India and correlated it with addiction status. METHODS: The study enrolled all subjects aged 60 years and above with 154 LC and 205 healthy controls. Genotyping was done by polymerase chain reaction (PCR) and validated by sequencing of 10% of the sample. Statistical analysis was done by SPSS Statistics 21. RESULTS: Genotype II was observed to have a significant 2.21-fold increased risk of LC as compared to the DD genotype and 3.43-folds enhanced risk with interaction of I allele with tobacco consumption habits as compared to D allele in LC was seen. CONCLUSION: The risk of LC was higher with II genotype as compared to DD genotype. Interactive effect showed that I allele with tobacco habits may increase the risk of LC.

Implementing and validating a care protocol for older adults with cancer in resource limited settings with a newly developed screening tool.

BACKGROUND: Cancer in the aging population presents manifold challenges. In the resource-limited settings of developing countries, concrete steps to optimize care for older adults with cancer are required. MATERIALS AND METHOD: This prospective, observational study was divided in two parts. In the first part, older adults (≥60 years) with a tissue diagnosis of cancer underwent a preliminary, detailed assessment of relevant geriatric domains. The patients were followed up at 4, 12 and 24 weeks, and their survival status was recorded. In the second part a newly developed screening tool, "SCreening of the Older PErson with Cancer", Version1 (SCOPE-C) was validated on patients with similar characteristics. RESULTS: 419 participants were enrolled in the study. The mean age of the participants was 66.6 ± 6.2 years, 75% had functional impairment, 35% had malnutrition, and 64% had more than one co-morbidity. The median survival time was 22 weeks from the index visit. Male gender, functional decline, cognitive impairment, malnutrition, and treatment modality were found to be independently associated with survival. Individual Scores on the SCOPE-C Version1 scale were correlated with survival status at 24 weeks, and a cutoff score of 64 had a 72.2% sensitivity and 77.3% specificity for better prognosis. CONCLUSION: The present study is a comprehensive attempt to assess older adults with cancer with limited resources in a busy health system. A preliminary assessment with a prognostic screening tool may streamline care in resource-limited settings and aid clinicians in making treatment decisions.

Sestrin2 as Serum Protein Marker and Potential Therapeutic Target for Parkinson's Disease.

Sestrin2 (Sesn2) appears to mediate neuroprotection against Parkinson's disease (PD)-associated pathophysiology, however, the mechanism is unknown. This pilot study examines serum Sesn2 level in PD patients and older adult control and also interrogates the rescue effect of Syzygium aromaticum extract on the neurotoxicity by paraquat in neuroblastoma cells. The blood sample was collected from 36 PD patients and 54 older adult control and concentration of serum Sesn2 was measured by surface plasmon resonance and western blot. A significantly elevated level of Sesn2 (p < .0001) was observed in sera of PD group (15.96 ± 2.428 ng/µL) than the control (13.65 ± 2.125 ng/µL) which was further confirmed by western blotting. The receiver operating characteristic (ROC) curve (0.76) determined the threshold value of ≥14.58 ng/µL for differentiating PD from control. The S aromaticum extract exhibited the rescue effect from paraquat induced toxicity in SH-SY5Y cells. Further, these cells showed dose-dependent downregulation of p53, Sesn2, and phosphorylated-AMPK with concomitant increase in phosphorylated-p70S6K level than paraquat-treated cells. The differential level of Sesn2 in study subjects proposes its utility as one of the potential serum markers in PD. The ethanolic extract of S aromaticum may serve as a novel platform for management of PD-associated neurotoxicity.

Biomarker-Based Prediction of Progression to Dementia: F-18 FDG-PET in Amnestic MCI.

BACKGROUND: Metabolic patterns on brain F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can predict the decline in amnestic mild cognitive impairment (aMCI) to Alzheimer's disease dementia (AD) or other dementias. OBJECTIVE: This study was undertaken to evaluate the diagnostic accuracy of baseline F-18 FDG-PET in aMCI for predicting conversion to AD or other dementias on follow-up. PATIENTS AND METHODS: A total of 87 patients with aMCI were enrolled in the study. Each patient underwent a detailed clinical and neuropsychological examination and FDG-PET at baseline. Each PET scan was visually classified based on predefined dementia patterns. Automated analysis of FDG PET was performed using Cortex ID (GE Healthcare). The mean follow-up duration was 30.4 ± 9.3 months (range: 18-48 months). Diagnosis of dementia at follow-up (obtained using clinical diagnostic criteria) constituted the reference standard, and all the included aMCI patients were divided into two groups: the aMCI converters (MCI-C) and MCI nonconverters (MCI-NC). Diagnostic accuracy of FDG PET was calculated using this reference standard. RESULTS: There were 23 MCI-C and 64 MCI-NC. Of the 23 MCI-C, 19 were diagnosed as probable AD, 1 as frontotemporal demetia (FTD), and 3 as vascular dementia (VD). Of the 64 MCI-NC, 9 had subjective improvement in cognition, and 55 remained stable. The conversion rate for all types of dementia in our series was 26.4% (23/87) and for Alzheimer's type dementia was 21.8% (19/87). The of PET-based visual interpretation was 91.9%. Sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET-based prediction of dementia conversion were 86.9% [confidence interval (CI) 66.4%-97.2%)], 93.7% (CI 84.7%-98.2%), 83.3% (CI 65.6%-92.9%), and 95.2% (CI 87.4%-98.9%), respectively. Kappa for agreement between visual and Cortex ID was 0.94 indicating excellent agreement. In the three aMCI patients progressing to VD, no specific abnormality in metabolic pattern was noted; however, there was marked cortical atrophy on computed tomography. CONCLUSION: FDG-PET-based visual and cortex ID classification has a good accuracy in predicting progression to dementia including AD in the prodromal aMCI phase. Absence of typical metabolic patterns on FDG-PET can play an important exclusionary role for progression to dementia. Vascular cognitive impairment with cerebral atrophy needs further studies to confirm and uncover potential mechanisms.

Status of VEGF in preeclampsia and its effect on endoplasmic reticulum stress in placental trophoblast cells.

OBJECTIVE: To explore the role of VEGF in attenuating endoplasmic reticulum stress in placental trophoblast cells. STUDY DESIGN: Study was divided into following parts: 1. Serum Analysis of GRP78 and VEGF using sandwich ELISA. 2. Expression of VEGF and GRP78 in placentae by immunohistochemistry (IHC). 3. In Vitro experiments. Status of ER stress markers (GRP78, eIF2α, XBP1, ATF6 and CHOP) was assessed at various time points (8 h, 14 h, 24 h) when trophoblast cells were treated with varying concentration(s) of VEGF and also by adding recombinant VEGF at protein (Immunofluorescence, Western blot) and transcript levels (qRT-PCR). RESULTS: Increased GRP78 and decreased VEGF protein levels in sera and placentae of preeclamptic pregnant women and reduced expression of various ER stress markers at both transcript and protein levels was observed in trophoblast cells when they were exposed to recombinant VEGF thereby indicating positive role of VEGF in alleviating ER stress. CONCLUSIONS: Reduced expression of ER stress markers in trophoblast cells against increased VEGF highlighted a new window to explore prospective drugs that can be designed to modulate the activities of various ER stress sensors in order to alleviate ER stress in pregnant women with preeclampsia.

Elevated Serum SIRT 2 May Differentiate Parkinson's Disease From Atypical Parkinsonian Syndromes.

Atypical Parkinson syndromes (APSs) often have symptoms that overlap with those of Parkinson's disease (PD), especially early in the disease, making these disorders difficult to diagnose. Previous studies have demonstrated an association of oligomeric α-synuclein (α-Syn), a key element in the pathogenesis of PD, with Sirtuin (SIRT)2 proteins for modulating PD. We aimed to evaluate SIRT protein expression in serum of PD patients and compare it with APSs and normal elderly control (GC) and to correlate this with α-Syn. SIRT protein expression was evaluated in sera of 68 PD; 34 APS and 68 GC without any neuro-psychiatric illness as controls by surface plasmon resonance (SPR). SIRT2 expression was correlated with α-Syn in PD and GC. Significant (p < 0.0001) differences were observed between serum SIRT2 concentration in PD and APS and GC as well as between APS and GC. Receiver operating characteristic (ROC) analysis revealed the strong cut-off value to differentiate PD from APS and GC and also APS from GC. Significant correlation was observed among SIRT2 levels in early PD patients with Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr (H & Y) and increased duration of disease. In addition, a strong positive correlation of SIRT2 with α-Syn (p < 0.0001) was observed. However, no such difference was detected for serum SIRT1 in cases of PD and APS or for GC. The present study is the first to report elevated serum SIRT2 in PD. The study also provided a simple test to distinguish PD from APS and may have translational utility for diagnosis.

Exploration of Novel Anti-Oxidant Protein Sestrin in Frailty Syndrome in Elderly.

Frailty in elderly is very much familiar with a decline in the musculoskeletal system. Muscle degeneration in the lower organism was observed due to loss of anti-oxidant protein Sestrin. The aim of the study is to determine the level of Sestrin1 and Sestrin2 in the serum of frail and non-frail elderly to associate their impact in frailty syndrome. Subjects with age ≥ 65 years were enrolled from Geriatric Medicine OPD of All India Institute of Medical Sciences, New Delhi (N= 92). Among them, 51 subjects were identified as frail and rest 41 were regarded as non-frail according to "deficit accumulation model of Rockwood." The study was performed by surface plasmon resonance and validated by western blot. Sestrin1 and Sestrin2 were found to be significantly reduced in frail compare to non-frail elderly. Furthermore, even after the adjustment for age, gender and education, the level of Sestrin1 and Sestrin2 remain significantly lower across the groups. The Sestrin1 level was significantly lower in various categories like age, gender, BMI, education, ADL, number of co-morbidity along with other clinico-pathological features. ROC analysis also revealed the distinction of frail and non-frail in respect to serum Sestrin1 and Sestrin2. This study highlighted the new and promising role of serum Sestrin in frail and non-frail elderly. In future, it can be utilized as molecular marker to assess the potential diagnostic value for clinical purpose.

Cyclin dependent kinase inhibitor 2A/B gene deletions are markers of poor prognosis in Indian children with acute lymphoblastic leukemia.

BACKGROUND: Cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) genes are implicated in many malignancies including acute lymphoblastic leukemia (ALL). These tumor suppressor genes, with a key regulatory role in cell cycle are located on chromosome 9p21.3. Previous studies involving CDKN2A/B gene deletions have shown mixed associations with survival outcome in childhood ALL. PROCEDURE: Hundred and four newly diagnosed children with ALL (1-14 years) were enrolled in this study. Genomic DNA from pretreatment bone marrow/peripheral blood samples of these children was investigated for copy number alterations in CDKN2A/B genes using multiplex ligation dependent probe amplification assay. Immunophenotype subtyping and cytogenetic and molecular analysis of ALL was performed at start of induction chemotherapy in all children. Children were monitored for response to prednisolone (Day 8), complete morphological remission, and minimal residual disease at the end of induction. The minimum postinduction follow-up period was 6 months. RESULTS: CDKN2A/B deletions were seen in 19.8% (18/91) of B lineage acute lymphoblastic leukemia (B-ALL) and 38.5% (5/13) of T lineage acute lymphoblastic leukemia (T-ALL). Monoallelic CDKN2A/B deletions were found in 61.1% of total deletions in B-ALL while all the children with T-ALL harbored biallelic deletions. The prevalence of CDKN2A/B gene deletions was found to be significantly higher in older children (P = 0.002), in those with higher leukocyte count (P = 0.037), and in National Cancer Institute high risk group patients (P = 0.001) in the B-ALL subgroup. Hazard ratio was significantly high for children with CDKN2A/B deletions in total cohort (P = 0.004). Children with CDKN2A/B deletion had significantly lesser event free survival (P = 0.03). CONCLUSIONS: CDKN2A/B deletions were significantly more prevalent in T-ALL subgroup and were found to have higher hazard ratio and lesser event free survival in total cohort in our study.

Effects of Tobacco Habits on the Polymorphism of NFKB1 and NFKB1A Gene of Head and Neck Squamous Cell Carcinoma in Indian Population

Background: Polymorphism of NFKB1 and NFKB1A are highly associated with cancer. We have assessed polymorphism in the promoter region of NFKB1 -94 del/ins ATTG (rs28362491) and NFKB1A -826 C/T (rs2233406) with the risk of HNSCC in Indian population. Methods: Polymerase chain reaction­restriction fragment length polymorphism (PCR-RFLP) method was used for the genotyping NFKB1 -94 del/ins ATTG and NFKB1A -826 C/T. Sequencing was done to validate the results of PCR-RFLP. Statistical analysis of data was done by Stata/SE-14.0 software. Results: ins/ins genotype was observed to be a risk factor of HNSCC as compared del/del genotype of NFKB1 -94 ATTG. Interactive effects of smoking and chewing on ins/ins genotype showed 13.96 and 10.92 fold increased risk of HNSCC. NFKB1A -826 C/T polymorphism, TT genotype showed no association with the risk of HNSCC as compared to wild type CC genotype. Conclusion: Our results showed NFKB1 -94 del/ins ATTG with smoking and tobacco chewing may increase the risk of HNSCC while NFKB1A -826 C/T plays a protective role in Indian population.

Promising link of HLA-G polymorphism, tobacco consumption and risk of Head and Neck Squamous Cell Carcinoma (HNSCC) in North Indian population.

Human leukocyte antigen (HLA-G) is a potent immune-tolerant molecule and has a critical role in various pathological conditions of cancer. The aim of the study was to analyze the association of HLA-G polymorphism as a risk factor in Head and Neck Squamous Cell Carcinoma (HNSCC). The HLA-G polymorphism at 3'UTR 14bp INDEL (rs371194629) and +3142G/C (rs1063320) were studied in 383 HNSCC patients and 383 ethnically similar-aged healthy controls in North Indian population. The genotyping study of two polymorphisms of HLA-G was documented using DNA-PAGE and RFLP-PCR method. 14bp INDEL Del/Ins, Ins/Ins genotype and Ins allele were more pronounced in HNSCC patients in compared to controls. Whereas, +3142 C/C genotype and C allele were associated with risk factors in HNSCC. Furthermore, the dual effect of polymorphisms; both variants (Del/Ins-Ins/Ins & G/C-C/C) carrying loci was significantly (OR=2.78) associated with the disease compared to one variant (Del/Del-G/C or Del/Del-C/C or Ins/Ins-G/G). Moreover, both polymorphisms showed promising link in terms of tobacco influence on HNSCC risk. It can be concluded that this study first time reports that C/C, Del/Ins and Ins/Ins genotype as well as C and Ins allele could be major risk factors with strong impact of tobacco for HNSCC in North Indian population.

Relative Alterations in Blood-Based Levels of Sestrin in Alzheimer's Disease and Mild Cognitive Impairment Patients.

Sestrins (sesn) are highly conserved proteins that play an important neuroprotective role, in part as a consequence of their antioxidative capacity, which prevents reactive oxygen species formation. In this study, we evaluated the concentrations of sesn1 and sesn2 in the serum of 41 Alzheimer's disease (AD) patients, 27 mild cognitive impairment (MCI), and 60 elderly controls, by surface plasmon resonance, which was validated by using western blot. Moreover, the mRNA level of sestrins in all the study groups was determined by real time polymerase chain reaction. The results showed significant overexpression of serum sesn2 protein and mRNA levels in the AD group compared to MCI and elderly control groups. A difference in serum sesn2 concentration between MCI and the control group was also evident. ROC analysis showed highly sensitive, selective cutoff values for sens2 in the differentiation of AD, MCI, and controls. No significant difference in sesn1 level was observed among the study groups. This study highlights the important role of sesn2 in the progression of the AD, indicating its potential utility as a protein marker in this devastating disease.

Estimation of Tau and Phosphorylated Tau181 in Serum of Alzheimer's Disease and Mild Cognitive Impairment Patients.

The elevated level of cerebrospinal fluid (CSF) Tau and phosphorylated Tau181 (p-Tau181) proteins are well established hallmarks of Alzheimer's disease (AD). Elevated level of p-Tau181 can differentiate AD from other neurodegenerative disease. However, the expression level of these proteins in serum of AD patient is not well set up. This study sought to evaluate the level of Tau and p-Tau181 in serum of AD, and mild cognitive impairment (MCI) patients for an alternative approach to establish protein-based markers by convenient way. Blood samples were collected from 39 AD patients, 37 MCI patients and 37 elderly individuals as controls. The levels of Tau and p-Tau181 in the serum of the different groups were measured by label free real time Surface Plasmon Resonance technology by using specific antibodies, and were further confirmed by the conventional western blot method. An appropriate statistical analysis, including Receiver Operating Characteristic (ROC), was performed. The concentrations of serum Tau and p-Tau181 were significantly higher (p<0.00001) in AD (Tau; 47.49±9.00ng/µL, p-Tau181; 0.161±0.04 ng/µL) compared to MCI (Tau; 39.26±7.78 ng/µL, p-Tau181; 0.135±0.02 ng/µL) and were further higher compared to elderly controls (Tau; 34.92±6.58 ng/µL, p-Tau181; 0.122±0.01 ng/ µL). A significant (p<0.0001) downhill correlation was found between Tau as well as p-Tau181 levels with HMSE and MoCA score. This study for the first time reports the concentration of Tau and p-Tau181 in serum of AD and MCI patients. The cutoff values of Tau and p-Tau181 of AD and MCI patients with sensitivity and specificity reveal that serum level of these proteins can be used as a predictive marker for AD and MCI.

Study of cytogenetic toxicity of low-dose radioiodine therapy in hyperthyroid patients using a micronuclei assay.

OBJECTIVE: Radioiodine, in low doses, has been used as a treatment modality for hyperthyroidism worldwide for a long time. However, there is little information available on the severity of cytotoxicity of radioiodine at these low doses. The present investigation aimed to study the cytogenetic toxicity of low-dose radioiodine in hyperthyroid patients using a cytokinesis-blocked micronuclei (MN) assay. MATERIALS AND METHODOLOGY: All of the patients received radioiodine in the form of sodium iodine (oral form). Blood samples of these patients were collected before therapy and 3 months after therapy, and lymphocytes were analysed for MN assay. RESULTS: Peripheral blood lymphocytes were analysed in 74 hyperthyroid patients (52 men, 22 women). The results indicated a positive relationship between age and the frequency of MN. However, there was no statistically significant difference in MN frequency at 3 months after therapy in comparison with that before therapy. CONCLUSION: This study showed that the cytogenetic damage produced by low-dose radioiodine was transient and reversible. Thus, patients can be motivated to undergo this safe and easy procedure as a modality of treatment for hyperthyroidism.

Population-based assessment of vision-related quality of life in corneal disease: results from the CORE study.

OBJECTIVE: To assess the impact of corneal disease on vision-related quality of life (VR-QoL) in a rural North Indian population. DESIGN: Cross-sectional, population-based study. METHODS: The Corneal Opacity Rural Epidemiological (CORE) study included 12 899 participants from 25 randomly selected clusters of rural Gurgaon, Haryana, India, with the primary objective of determining the prevalence of corneal disease in the general population during July 2011 to January 2013. VR-QoL was assessed through Indian Vision Function questionnaire (IND-VFQ-33) in adult participants (aged ≥18 years) detected with corneal opacity and equal number of healthy controls (no ocular pathology with visual acuity of 6/6 binocularly) selected from the same clusters. Scores of the three subscales of IND-VFQ-33 (vision-specific mobility, psychosocial impact and visual symptoms) were computed, analysed and compared separately across various groups. RESULTS: Overall, 12 113 participants of all ages underwent detailed ophthalmic examination and VR-QoL was assessed in 435 cases with corneal disease and 435 controls without any ophthalmic disease. The diseased population had significantly higher scores and hence poorer VR-QoL across all three domains of vision function (scores of 28 vs 22; 6 vs 5 and 14 vs 9, respectively; p<0.0001) and the scores were inversely related with the level of visual impairment in patients with corneal disease. Patients with unilateral corneal disease also had poorer VR-QoL scores as compared with healthy controls (p<0.0001). CONCLUSIONS: VR-QoL is impaired in patients with corneal disease, more so in patients with corneal blindness. This is the first population-based study to document VR-QoL through IND-VFQ-33 in the Indian population with corneal disease.

Prevalence of corneal diseases in the rural Indian population: the Corneal Opacity Rural Epidemiological (CORE) study.

OBJECTIVE: The present population-based study was undertaken to estimate the prevalence, determinants and causes of corneal morbidity and blindness in a rural North Indian population. DESIGN: Population-based study in India with 12 899 participants of all ages. METHODS: Participants were recruited from 25 village clusters of district Gurgaon, Haryana, India using random cluster sampling strategy. All individuals were examined in detail with a portable slit lamp for evidence of any corneal disease during the door-to-door examination. Comprehensive ocular examination including logMar visual acuity, slit lamp biomicroscopy, non-contact tonometry and dilated retinal evaluation was performed at a central clinic site in the respective villages. RESULTS: Overall, 12 113 of 12 899 people (93.9% response rate) were examined during the household visits. Prevalence of corneal disease was 3.7% (95% CI 3.4% to 4.1%) and that of corneal blindness was 0.12% (95% CI 0.05% to 0.17%). Multivariable analysis demonstrated that corneal disease was significantly higher in the elderly (p<0.0001) and illiterates (p<0.0001). Common causes of corneal opacity in the study population were pterygium (34.5%), ocular trauma (22.3%) and infectious keratitis (14.9%). Corneal diseases contributing to blindness were post-surgical bullous keratopathy (46.2%) and corneal degenerations (23.1%). CONCLUSIONS: The study findings demonstrate that currently ocular trauma, infectious keratitis, post-surgical bullous keratopathy, and corneal degenerations are responsible for the major burden of corneal blindness and morbidity in the Indian population. The prevalence of corneal morbidity due to vitamin A deficiency and trachoma was low in this rural population.