An insight into the pharmacology of cysteine/methionine containing peptide drugs.

Since last century, peptides have emerged as potential drugs with >90 FDA approvals for various targets with several in the pipeline. Sulphur, in peptides is present either as thiol (-SH) from Cys or thioether from Met. In this review, all the peptides approved by FDA since 2000 containing sulphur have been included. Among them ∼50 % contains disulphide bridges. This clearly demonstrates the significance of disulphide bonds in peptide drugs. This can be achieved synthetically by using orthogonal protecting groups (PGs) for -SH. These PGs are compatible with Solid Phase Peptide Synthesis (SPPS), which is still the method of choice for peptide synthesis. The orthogonal PGs used for Cys thiol side chain protecting for disulphide bond formation have been included which are currently in use both by academia and industry from small scale to large scale synthesis. In addition, the details of the FDA approved drugs containing Cys and Met (or both) have also been discussed.

The effect of COVID-19 on the non-COVID health outcomes of crisis-affected peoples: a systematic review.

BACKGROUND: The COVID-19 pandemic posed considerable risks to populations affected by humanitarian crises in low- and middle-income countries (LMICs). However, there is limited understanding of how the pandemic may have affected non-COVID health outcomes among crisis-affected populations. Our aim was to examine the evidence on the impact of the COVID-19 pandemic on non-COVID-19 health outcomes for crisis-affected populations in LMICs. METHODS: A systematic review methodology was applied following PRISMA guidelines. Eligibility criteria were: crisis-affected populations in LMICS; COVID-19; and all health topics, except for sexual and reproductive health which was covered in a linked review. Five bibliographic databases and additional grey literature sources were searched. The search period was from 2019 to 31 July 2022. Eligible papers were extracted and analysed using a narrative synthesis approach based on the study objectives and relevant health access and systems frameworks. A quality appraisal was also conducted. FINDINGS: 4320 articles were screened, and 15 eligible studies were identified and included in this review. Ten studies collected health outcomes data. Eight related to mental health, which generally showed worse mental health outcomes because of the pandemic, and pandemic-related stressors were identified. Two studies assessed physical health outcomes in children, while none addressed physical health outcomes among adults. Nine studies reported on access to healthcare, revealing worse access levels due to the pandemic and noting key barriers to care. Seven studies reported on the impact on health systems, with key challenges including reduced and distorted health care funding, reduced staff capacity, interrupted medicines and supplies, weak information and mixed-messaging, and weak leadership. All fifteen studies on the social determinants of health, particularly highlighting the effect of increasing poverty, the role of gender, and food insecurity on health outcomes. The quality of papers was limited overall. CONCLUSION: This review found some limited evidence indicating negative mental health effects, increased barriers to accessing care, damage to health systems and magnified impacts on the social determinants of health for crisis-affected people during the COVID-19 pandemic. However, the small number and limited quality of the studies make the overall strength of evidence quite weak.

Utility of a machine-guided tool for assessing risk behaviour associated with contracting HIV in three sites in South Africa.

Introduction: Digital data collection and the associated mobile health technologies have allowed for the recent exploration of artificial intelligence as a tool for combatting the HIV epidemic. Machine learning has been found to be useful both in HIV risk prediction and as a decision support tool for guiding pre-exposure prophylaxis (PrEP) treatment. This paper reports data from two sequential studies evaluating the viability of using machine learning to predict the susceptibility of adults to HIV infection using responses from a digital survey deployed in a high burden, low-resource setting. Methods: 1036 and 593 participants were recruited across two trials. The first trial was a cross-sectional study in one location and the second trial was a cohort study across three trial sites. The data from the studies were merged, partitioned using standard techniques, and then used to train and evaluate multiple different machine learning models and select and evaluate a final model. Variable importance estimates were calculated using the PIMP and SHAP methodologies. Results: Characteristics associated with HIV were consistent across both studies. Overall, HIV positive patients had a higher median age (34 [IQR: 29-39] vs 26 [IQR 22-33], p < 0.001), and were more likely to be female (155/703 [22%] vs 107/927 [12%], p < 0.001). HIV positive participants also had more commonly gone a year or more since their last HIV test (183/262 [70%] vs 540/1368 [39%], p < 0.001) and were less likely to report consistent condom usage (113/262 [43%] vs 758/1368 [55%], p < 0.001). Patients who reported TB symptoms were more likely to be HIV positive. The trained models had accuracy values (AUROCs) ranging from 78.5% to 82.8%. A boosted tree model performed best with a sensitivity of 84% (95% CI 72-92), specificity of 71% (95% CI 67-76), and a negative predictive value of 95% (95% CI 93-96) in a hold-out dataset. Age, duration since last HIV test, and number of male sexual partners were consistently three of the four most important variables across both variable importance estimates. Conclusions: This study has highlighted the synergies present between mobile health and machine learning in HIV. It has been demonstrated that a viable ML model can be built using digital survey data from an low-middle income setting with potential utility in directing health resources.

Mössbauer spectroscopic investigations on iron oxides and modified nanostructures: A review.

Pure and doped iron oxide and hydroxide nanoparticles are highly potential materials for biological, environment, energy and other technological applications. On demand of the applications, single phase as well as multiple phase of different polymorphs or composites of iron oxides with compatible materials for example, zeolite, SiO2, or Au are prepared. The properties of the as-synthesized nanoparticles are predominantly dictated by the local structure and the distribution of the cations. Mössbauer spectroscopy is a perfect and efficient characterization technique to investigate the local structure of the Mössbauer-active element such as Fe, Au, and Sn. In the present review, the local structure transformation on the optimization of the magnetite coexisted with iron hydroxides, spin dynamics of the bare, caped, core-shell and the composites of iron oxide nanoparticles (IONPs), dipole-dipole interactions and the diffusion of IONPs were discussed, based on the findings using Mössbauer spectroscopy.

Anti-Acanthamoeba activity of a semi-synthetic mangostin derivative and its ability in removal of Acanthamoeba triangularis WU19001 on contact lens.

Garcinia mangostana L., also known as the mangosteen tree, is a native medicinal plant in Southeast Asia having a wide variety of pharmacologically active compounds, including xanthonoid mangostin. In this study, we examined the pharmacological activities of the selected semi-synthetic mangostin derivative, namely, amoebicidal activity, encystation inhibition, excystation activity, and removal capacity of adhesive Acanthamoeba from the surface of contact lens (CL). Among the three derivatives, C1 exhibited promising anti-Acanthamoeba activity against Acanthamoeba triangularis WU19001 trophozoites and cysts. SEM images displayed morphological changes in Acanthamoeba trophozoites, including the loss of acanthopodia, pore formation in the cell membrane, and membrane damage. In addition, the treated cyst was shrunken and adopted an irregular flat cyst shape. Under a fluorescence microscope, acridine orange and propidium iodide (AO/PI) staining revealed C1 induced condensation of cytoplasm and chromatin with the loss of cell volume in the treated trophozoites, while calcofluor white staining demonstrated the leakage of cell wall in treated cysts, leading to cell death. Interestingly, at the concentration ranges in which C1 showed the anti-Acanthamoeba effects (IC50 values ranging from 0.035-0.056 mg/mL), they were not toxic to Vero cells. C1 displayed the highest inhibitory effect on A. triangularis encystation at 1/16×MIC value (0.004 mg/mL). While C1 demonstrated the excystation activity at 1/128×MIC value with a high rate of 89.47%. Furthermore, C1 exhibited the removal capacity of adhesive Acanthamoeba from the surface of CL comparable with commercial multipurpose solutions (MPSs). Based on the results obtained, C1 may be a promising lead agent to develop a therapeutic for the treatment of Acanthamoeba infections and disinfectant solutions for CL.

Upgrade of the helically symmetric experiment Thomson scattering diagnostic suite.

The Helically Symmetric eXperiment (HSX) Thomson Scattering (TS) diagnostic is being upgraded to decrease uncertainty in electron temperature and density measurements. Upgrades to the HSX TS diagnostic will consist of a novel redesign of polychromator electronics and digitization of the TS output signal. Here, we also present a study of the benefits of an additional spectral channel that will sample the red-shifted band of the scattered spectrum. To maximize system bandwidth (BW) and gain, while minimizing noise, the existing low-BW polychromator electronics on HSX will be replaced by high-BW, high gain circuitry designed in-house.

Investigation of Thermoluminescence (TL) and Optically Stimulated Luminescence (OSL) Properties of Dy3+ Doped CaB4O7 Nanoparticles.

CaB4O7 nanoparticles doped with different concentrations of Dy3+ were prepared by using solution combustion method. The recorded Thermoluminescence (TL) and Optically stimulated luminescence (OSL) of CaB4O7:Dy samples for different concentrations of Dy3+ irradiated with 6 Gy of X-Ray shows concentration quenching effect above 0.05 at.wt% of Dy3+ concentrations. The TL and OSL kinetic parameters of glow curves were evaluated using "tgcd" and conventional fitting methods. The TL glow curve of the CTB:(0.05%)Dy have five individual glow peaks with maximum peak temperatures at 410, 470, 525, 563 and 593 K. TL Dose response of the X-Ray irradiated CTB:(0.05%)Dy is also found to be linear in the range of 1 Gy to 50 Gy. The OSL glow curves of the CTB:Dy nanoparticles follow non-first order kinetics and can be fitted with the sum of three first order decay curves. Fading characteristics of the TL and OSL signals are studied for 40 days and found to be very stable.

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

Water budgeting in conservation agriculture-based sub-surface drip irrigation in tropical maize using HYDRUS-2D in South Asia.

In water scarce regions of South Asia, diversification of rice with maize is being advocated towards sustainability of cereal-based cropping systems. Adoption of innovative agronomic management practices, i.e., conservation agriculture (CA) and sub-surface drip irrigation (SSDI) are considered as key strategies for much needed interventions to address the challenges of water scarcity under projected climate change. Benefits from CA and SSDI concerning water economy are well-established, however, information about their complementarity and water budgeting in cereal-based systems are lacking. A field study was conducted with process-based model (HYDRUS-2D) to understand water transport, root water uptake and components of soil water balance in maize grown in rotation with wheat after five years of continuous adoption of conservation agriculture. In this study, altogether eight treatments comprising of 6 CA+ treatments (CA coupled with SSDI); permanent beds using sub-surface drip (PB-SSD) with (WR) and without (WOR) crop residue at different N rates, 0, 120 and 150 kg N ha-1 were compared with CA (PB using furrow irrigation-FI with crop residue-120 kg N ha-1) and conventional tillage practices (CT) (CT using FI without crop residue-120 kg N ha-1). Results showed that the model could simulate the daily changes in profile soil water content with reasonable accuracy in all the treatments. Simulated soil water balance indicated higher cumulative root water uptake (CRWU), lower cumulative evaporation (CE) and higher soil water retention in CA+ (PB-SSD+ crop residue at 150 and 120 kg N ha-1) than CA and CT plots. Hydrus-2D model efficiency > 0, RMSE between 0.009-0.026 and R2 value between 0.80-0.92 at P < 0.01 indicates that the model is performing efficiently. The mean evaporation from CA+ treatments was 10 and 36% less than CA and CT treatments, respectively. On average, CRWU under CA+ treatments were 14-48% higher than FI treatments. The mean cumulative deep drainage in CA+ plots was 80-100 mm less than CA and CT plots. In CA+ based plots significantly higher biomass production and radiation use efficiency were observed with reduced water use than CA and CT. Therefore, the study justifies the water-saving nature of CA+, while maintaining higher productivity and meeting the transpiration demand of crops and halting unnecessary evaporation and deep drainage losses.

Energy and carbon budgeting of traditional land use change with groundnut based cropping system for environmental quality, resilient soil health and farmers income in eastern Indian Himalayas.

Energy intensive traditional cereals based monoculture often lead to high greenhouse gas emissions and degradation of land and environmental quality. Present study aimed at evaluating the energy and carbon budget of diversified groundnut (Arachis hypogea L) based cropping system with over existing traditional practice towards the development of a sustainable production technology through restoration of soil and environmental quality and enhancement of farming resiliency by stabilizing farmers' income. The trials comprised of three introduced groundnut based systems viz. groundnut- pea (Pisum sativum), groundnut-lentil (Lens esculenta) and groundnut-toria (Brasssica campestris var. Toria) replacing three existing systems viz. maize (Zea mays L) - fallow, maize - toria, and rice (Oryza sativa L)-fallow systems. Four years study revealed that adoption of groundnut based systems reduced non-renewable energy input use (fertilizers, chemical, machinery and fossil fuels) by 25.5%, consequently that reduced the cost of production. Repeated analysis of variance measurement also affirmed that groundnut based systems (groundnut-pea>groundnut-lentil> groundnut-toria) increased the energy use efficiency, energy productivity, carbon use efficiency, net returns and decreased the specific energy and energy intensiveness. Groundnut based systems increased the mean system productivity and water productivity in terms of groundnut equivalent yield by 3.7 and 3.1 folds over existing practice. The savings of fossil fuel reduced greenhouse gas emissions owing to reduced use of farm machinery and synthetic fertilizers. Groundnut based systems significantly (p < 0.05) enhanced the soil carbon concentration (8.7-18.1%) and enzymatic activities (27.1-51.8%) over existing practice. Consequently, estimated soil quality index values were 35.9-77.3% higher under groundnut based systems than existing practice. Thus, the study indicated the resilient nature of groundnut based systems as an environmentally safe and sustainable production technology for enhancing resource use efficiency, reduce carbon emission, energy intensiveness and cost of production in the Eastern Himalaya region of India and similar ecosystems.

Synthetic approaches to FDA approved drugs for asthma and COPD from 1969 to 2020.

Respiratory infections resulting from pulmonary inflammation emerging as a leading cause of death worldwide. However, only twenty-seven new drugs were approved in the last five decades. In this review, we presented synthetic approaches for twenty-seven FDA-approved medications used to treat asthma and chronic obstructive pulmonary diseases (COPD), along with their mode of action.

Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma.

PURPOSE: Molecular mechanisms of uveal melanoma development in association with high pigmentation are unclear. Tyrosinase Related Protein (TYRP1) is not only one of the important melanogenesis marker that contributes to melanin synthesis, but can also prevents the melanocyte death. The induction of melanogenesis leads to induction of HIF-1α which can affect the behavior of melanoma cells and its surrounding environment. The aim of our study was to determine the expression of TYRP1 and HIF-1α at the protein and RNA level and determine its prognostic significance. METHODS: In the present study, the expression of TYRP1 and HIF-1α was investigated on 61 formalin-fixed paraffin-embedded choroidal melanoma samples by immunohistochemistry. Fresh 50 samples were validated by real-time PCR. Results were correlated with clinicopathological parameters and Kaplan-Meier was performed to determine the prognostic significance. RESULTS: High immunoexpression of TYRP1 and HIF-1α was present in 61 and 54% of patients, respectively. Both TYRP1 and HIF-1α correlated well with high pigmentation and BAP1 (BRCA1 Associated Protein-1) loss (p < 0.05) at IHC level as well as transcriptional level. There was reduced metastatic free survival in patients with necrosis and this was statistically significant (p = 0.010). CONCLUSION: Our findings indicate that TYRP1 can be used as a potential biomarker in the development of targeted therapy in UM. Further studies on melanogenesis markers associated with TYRP1 could provide us a better understanding in this field.

Productive and reproductive performances of two-breed and three-breed pig crosses with Niang Megha, Hampshire and Duroc inheritance reared under subtropical Eastern Himalayan hilly climate.

The objective of the study was to evaluate the performance of different crossbreeds, viz., two-breed crosses including HN-50 (50% Hampshire × 50% Niang Megha) and HN-75 (75% Hampshire × 25% Niang Megha) and three-breed cross, HND (25% Hampshire × 25% Niang Megha × 50% Duroc) for suggesting suitable crossbred pigs with appropriate inheritance for subtropical Eastern Himalayan hilly climate. These crossbreed pigs were reared in standard management conditions in Nucleus Pig Breeding Farm of ICAR RC for NEH region. A total of 1995 records were collected which included data on production performance (n = 1466), reproductive performance (n = 428) and carcass traits (n = 101) from farm record book maintained over a period of 7 years. Productive performance included body weight, ADG and FCR at different stages of growth. The study revealed productive performance was highest in two-breed cross of pigs with 75% H inheritance (HN-75) and three-breed cross (HND) pigs. Reproductive performance included ages at puberty, first conception and first farrowing, along with inter-farrowing interval, pregnancy and farrowing rate as well as litter performance. The HN-75 was found to be having shorter inter-farrowing interval and higher pregnancy rate than other genetic groups. Regarding carcass traits, three-breed cross had a higher dressing percentage and less back-fat thickness than other crossbred pigs. Two breed crosses of pigs were found to be having a higher back-fat thickness than three-breed cross pig, and HN-75 had a better dressing percentage than HN-50. Thus, it was concluded that three-breed cross was recommended for lean meat production, and two-breed cross HN-75 was recommended for both breeding and fattening purposes for subtropical Eastern Himalayan hilly climate.

Microwave-assisted efficient synthesis of pyrazole-fibrate derivatives as stimulators of glucose uptake in skeletal muscle cells.

The design and synthesis of a series of pyrazolo[3,4-d]pyrimidinones containing fibrate side chains have been accomplished by utilizing the concept of molecular hybridization. All the synthesized compounds were evaluated for the glucose uptake stimulatory effect in L6 rat skeletal muscle cells. Four compounds (3f, 3g, 3j and 3q) were found to show significant stimulation of glucose uptake. Further these four compounds have been examined for their Glut4 translocation stimulatory effect in L6-Glut4myc myotubes. Compound 3q was found to exert maximum increase in GLUT4myc translocation.

Possible mechanism of bamboo shoots (Bambusa balcooa) induced thyroid disruption - An in vitro study.

Endemic goitre and associated iodine deficiency disorders (IDDs) are a major concern in public health even in the period of post salt iodization in many regions. Among others the consumption of cyanogenic plants found responsible for the persistence of such diseases. Bamboo shoots (BS) is one such cyanogenic plant food that caused disruption of certain thyroid hormone synthesizing regulatory element as has already been reported in our earlier study. In this investigation the possible mechanism of thyrocytes disruption along with interruption of thyroid hormone biosynthesis by BS has been worked out. Commonly consumed BS, Bambusa Balcooa Roxb (BBR) water extract was analysed by GC MS; three doses below IC50 were administered to thyrocytes in culture with and without iodine. Expressions of thyroglobulin (Tg), pendrin (PDS) and monocarboxylate transporter 8 (MCT8) were evaluated in thyrocytes with cell cycle analysis, reactive oxygen species (ROS) generation, DNA oxidation and apoptotic regulation through Bax, Bcl-2 and p53. Phytochemical analysis of BBR extract revealed the presence of precursors and metabolic end products of cyanogenic glycosides. Dose dependent decrease in expression of Tg and PDS with concomitant decrease in gene expression of these with MCT8 were observed. Increased ROS, DNA oxidation and associated imbalance were found through increased Bax and p53 with decreased Bcl-2 that perturbed thyrocytes cell cycle. Cyanogenic constituents of BBR generates ROS associated oxidative changes in thyrocytes with DNA damage and oxidation and cell cycle disruption followed by inhibition of thyroid hormone synthesizing regulatory elements; addition of extra iodine showed partial prevention.

Functionality study of chalcone-hydroxypyridinone hybrids as tyrosinase inhibitors and influence on anti-tyrosinase activity.

In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalcone-hydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds 1a, 1d, and 1n had relatively strong inhibitory activities against tyrosinase monophenolase, with IC50 values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 µM, respectively. The inhibitory activity against monophenolase was 6- to 8-fold higher than that of kojic acid. Compounds 1a, 1d, and 1n also showed inhibition of diphenolase, with IC50 values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 µM, respectively. The inhibition kinetics of diphenolase indicates that compounds 1a and 1d induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.

Alkali-cation-incorporated and functionalized iron oxide nanoparticles for methyl blue removal/decomposition.

Enhancing the rate of decomposition or removal of organic dye by designing novel nanostructures is a subject of intensive research aimed at improving waste-water treatment in the textile and pharmaceutical industries. Despite radical progress in this challenging area using iron-based nanostructures, enhancing stability and dye adsorption performance is highly desirable. In the present manuscript alkali cations are incorporated into iron oxide nanoparticles (IONPs) to tailor their structural and magnetic properties and to magnify methyl blue (MB) removal/decomposition capability. The process automatically functionalizes the IONPs without any additional steps. The plausible mechanisms proposed for IONPs incubated in alkali chloride and hydroxide solutions are based on structural investigation and correlated with the removal/adsorption capabilities. The MB adsorption kinetics of the incubated IONPs is elucidated by the pseudo second-order reaction model. Not only are the functional groups of -OH and -Cl attached to the surface of the NPs, the present investigation also reveals that the presence of alkali cations significantly influences the MB adsorption kinetics and correlates with the cation content and atomic polarizability.

Analysis of trap distribution of a red persistent luminescent materials using thermoluminescence.

Trap distribution plays a crucial role in deciding the applicability of a material. The thermoluminescence (TL) parameter that describes trap distribution is η, which has never been discussed in TL analysis so far. TL analysis of a commercially available red persistent luminescent material (CaSrS:Eu) was performed using computerized glow curve deconvolution (CGCD) in the new general order kinetics. CGCD results showed that the red persistent luminescent material in the temperature range 300-600º K was comprised of nine peaks. Activation energy ranged from 0.66-1.27 eV. Frequency factor was in the range 109 to 1011 sec-1 . The major peaks of the red persistent luminescent material had lesser empty traps. The most important information provided by the analysis was that the major peaks of the red persistent luminescent material had 30-60% of the empty traps close to the filled traps, and this accounted for retrapping of thermally released electrons. This finding suggests that the occurrence of 30-60% empty traps close to the filled traps is a necessary requisite for a persistent luminescent material.

DNA damage response proteins and its role in tumor progression of uveal melanoma with patient outcome.

BACKGROUND: The role of DNA damage response (DDR) proteins is poorly understood in uveal melanoma. ATR belongs to one of those proteins that induce DDR by arresting the cell cycle which leads to DNA repair. ATR is localized at position 23 on the same chromosome 3 where BAP1 is located at position 21.1 which is a known poor prognostic marker of UM. The aim of our study is to detect the expression of ATR at the protein and RNA levels and determine its prognostic significance. METHODS: Expression of nuclear ATR was investigated on sixty-nine UM patients. Formalin-fixed paraffin-embedded choroidal melanoma samples were taken to evaluate the expression of ATR. Fifty samples were also validated by real-time PCR. Results of both protein and mRNA were then correlated with clinicopathological parameters. To determine the prognostic significance, Kaplan-Meier and multivariate analyses were performed. RESULTS: Loss of ATR protein was seen in 72% cases which was statistically significant with epithelioid cell type (p = 0.005), tumor thickness (p = 0.016), mitotic figures (p = 0.001) and BAP1 loss (p < 0.001). At the transcriptional level loss of ATR was seen in 76% cases which were statistically significant with metastasis (p = 0.046), staging (0.044) and loss of BAP1 (p = 0.022). On multivariate analysis loss of ATR and tumor staging came out to be independent prognostic parameters. CONCLUSION: Our data suggest that ATR might serve as a potential prognostic marker in UM patients and could serve as a potential therapeutic target.