1,3-Thiazole Derivatives as a Promising Scaffold in Medicinal Chemistry: A Recent Overview.

The thiazole ring is a unique heterocyclic motif among heterocyclic compounds. This five-member ring with one nitrogen and one sulphur atom displays a wide array of pharmacological activities, including anti-inflammatory, antimicrobial, anticancer, antidiabetic, antiviral, etc., by acting on several targets. Its broad range of medical applications has inspired us to study this opulent heterocyclic molecule. The current review summarizes synthetic approaches for the preparation of thiazole derivatives in brief and discusses the promising biological activities of this scaffold. This review will be useful to the drug discovery community and will facilitate the synthesis and development of novel and potent thiazole derivatives, which may serve as lead molecules for the treatment of various diseases.

Anomalous magnetoresistance by breaking ice rule in Bi2Ir2O7/Dy2Ti2O7 heterostructure.

While geometrically frustrated quantum magnets host rich exotic spin states with potentials for revolutionary quantum technologies, most of them are necessarily good insulators which are difficult to be integrated with modern electrical circuit. The grand challenge is to electrically detect the emergent fluctuations and excitations by introducing charge carriers that interact with the localized spins without destroying their collective spin states. Here, we show that, by designing a Bi2Ir2O7/Dy2Ti2O7 heterostructure, the breaking of the spin-ice rule in insulating Dy2Ti2O7 leads to a charge response in the conducting Bi2Ir2O7 measured as anomalous magnetoresistance during the field-induced Kagome ice-to-saturated ice transition. The magnetoresistive anomaly also captures the characteristic angular and temperature dependence of this ice-rule-breaking transition, which has been understood as magnetic monopole condensation. These results demonstrate a novel heteroepitaxial approach for electronically probing the transition between exotic insulating spin states, laying out a blueprint for the metallization of frustrated quantum magnets.

Different Treatments for Sugarcane Juice Preservation.

This investigation aimed to optimize the time, pH, pressure, and temperature of sugarcane juice pasteurization and to develop a "ready to serve" bottled sugarcane juice with a high preservation efficiency. Fresh sugarcane juice was extracted from sugarcane genotype Co 89003, and beverage samples were collected using three different treatments: sulphitation of juice with the addition of potassium metabisulphite (KMS-25, 50, 100, and 150 ppm), acidification of juice (addition of citric acid, to reduce the pH of the juice to 4.8, 4.5, and 4.25), and steam treatment of the canes (5 min, 10, and 15 min at 7 psi). In all treatments, the juice was pasteurized in glass bottles @ 65 °C for 25 min and stored at low temperature (5 °C) in pre-sterilized glass bottles. Juice properties such as the ˚Brix, total sugar, pH, and total phenolic content decreased with storage, whereas the microbial count, titrable acidity, and reducing sugar content significantly increased during storage. The addition of KMS, citric acid, and the steam treatment reduced the browning of juice and maintained the color of juice during storage, by inhibiting the polyphenol oxidase enzyme activity, from 0.571 unit/mL to 0.1 unit/mL. Among the selected treatments, sugarcane juice with KMS (100 and 150 ppm) and steam treatment of the canes for 5 and 10 min at 7 psi showed the minimum changes in physico-chemical properties, sensory qualities, and restricted microbial growth. Thesulphitation treatment with pasteurization proved best for increasing the shelf life of sugarcane juice upto 90 days with refrigeration. Similarly, the steam-subjected cane juice (10 and 15 min at 7 psi) could be effectively preserved for upto 30 days with refrigeration, without any preservative.

Self-Organizing Democratized Learning: Toward Large-Scale Distributed Learning Systems.

Emerging cross-device artificial intelligence (AI) applications require a transition from conventional centralized learning systems toward large-scale distributed AI systems that can collaboratively perform complex learning tasks. In this regard, democratized learning (Dem-AI) lays out a holistic philosophy with underlying principles for building large-scale distributed and democratized machine learning systems. The outlined principles are meant to study a generalization in distributed learning systems that go beyond existing mechanisms such as federated learning (FL). Moreover, such learning systems rely on hierarchical self-organization of well-connected distributed learning agents who have limited and highly personalized data and can evolve and regulate themselves based on the underlying duality of specialized and generalized processes. Inspired by Dem-AI philosophy, a novel distributed learning approach is proposed in this article. The approach consists of a self-organizing hierarchical structuring mechanism based on agglomerative clustering, hierarchical generalization, and corresponding learning mechanism. Subsequently, hierarchical generalized learning problems in recursive forms are formulated and shown to be approximately solved using the solutions of distributed personalized learning problems and hierarchical update mechanisms. To that end, a distributed learning algorithm, namely DemLearn, is proposed. Extensive experiments on benchmark MNIST, Fashion-MNIST, FE-MNIST, and CIFAR-10 datasets show that the proposed algorithm demonstrates better results in the generalization performance of learning models in agents compared to the conventional FL algorithms. The detailed analysis provides useful observations to further handle both the generalization and specialization performance of the learning models in Dem-AI systems.

Controllable Emergent Spatial Spin Modulation in Sr_{2}IrO_{4} by In Situ Shear Strain.

Symmetric anisotropic interaction can be ferromagnetic and antiferromagnetic at the same time but for different crystallographic axes. We show that the competition of anisotropic interactions of orthogonal irreducible representations can be a general route to obtain new exotic magnetic states. We demonstrate it here by observing the emergence of a continuously tunable 12-layer spatial spin modulation when distorting the square-lattice planes in the quasi-two-dimensional antiferromagnetic Sr_{2}IrO_{4} under in situ shear strain. This translation-symmetry-breaking phase is a result of an unusual strain-activated anisotropic interaction which is at the fourth order and competing with the inherent quadratic anisotropic interaction. Such a mechanism of competing anisotropy is distinct from that among the ferromagnetic, antiferromagnetic, and/or the Dzyaloshinskii-Moriya interactions, and it could be widely applicable and highly controllable in low-dimensional magnets.

Sternocleidomastoid flap for pedicled reconstruction in head & neck surgery- revisiting the anatomy and technique.

BACKGROUND: Previous studies on sternocleidomastoid flaps, have defined the importance of preserving sternocleidomastoid (SCM) branch of superior thyroid artery (STA). This theory drew criticism, as this muscle is known to be a type II muscle, i.e., the muscle has one dominant pedicle (branches from the occipital artery at the superior pole) and smaller vascular pedicles entering the belly of muscle (branches from STA and thyrocervical trunk) at the middle and lower pole respectively. It was unlikely for the SCM branch of STA to supply the upper and lower thirds of the muscle. We undertook a cadaveric angiographic study to investigate distribution of STA supply to SCM muscle. METHODS: It is a cross-sectional descriptive study on 10 cadaveric SCM muscles along with ipsilateral STA which were evaluated with angiography using diatrizoate (urograffin) dye. Radiographic films were interpreted looking at the opacification of the muscle. Results were analyzed using frequency distribution and percentage. RESULTS: Out of ten specimens, near complete opacification was observed in eight SCM muscle specimens. While one showed poor uptake in the lower third of the muscle, the other showed poor uptake in the upper third segment of muscle. CONCLUSION: Based on the above findings we suggest to further investigate sternocleidomastoid muscle as a type III flap, as the STA branch also supplies the whole muscle along with previously described pedicle from occipital artery. However, this needs to be further corroborated intra-operatively using scanning laser doppler. This also explains better survival rates of superior thyroid artery based sternomastoid flaps.

Risk Assessment of Aerosol Generation During Vitreoretinal Surgery Using High Speed Imaging Amidst the COVID-19 Pandemic.

Purpose: The purpose of this study was to discuss the propensity of aerosol and droplet generation during vitreoretinal surgery using high speed imaging amidst the coronavirus disease 2019 (COVID-19) pandemic. Methods: In an experimental set up, various steps of vitreoretinal surgery were performed on enucleated goat eyes. The main outcome measures were visualization, quantification of size, and calculation of aerosol spread. Results: During intravitreal injection, insertion of cannulas, lensectomy, and vitrectomy with both 23 and 25-gauge instruments, with either valved or nonvalved cannulas, aerosols were not visualized which was confirmed on imaging. Although there was no aerosol generation during active fluid air exchange (FAE), there was bubbling and aerosol generation at the exit port of the handle during passive FAE. Under higher air pressure, with reused valved and fresh nonvalved cannulas, aerosol generation showed a trajectory 0.4 to 0.67 m with droplet size of 200 microns. Whereas removing cannulas or suturing under active air infusion (35 mm Hg and above) aerosols were noted. Conclusions: Based on the above experiments, we can formulate guidelines for safe vitrectomy during COVID-19. Some recommendations include the use of valved cannulas, avoiding passive FAE or to direct the exit port away from the surgeon and assistant, and to maintain the air pressure less than or equal to 30 mm Hg. Translational Relevance: In the setting of the COVID-19 pandemic, the risk from virus laden aerosols, as determined using an experimental setup, appears to be low for commonly performed vitreoretinal surgical procedures.

Biomass potential of novel interspecific and intergeneric hybrids of Saccharum grown in sub-tropical climates.

Sugarcane-derived biomass is a promising source of renewable energy to meet the growing demands for biofuel. Currently, modern sugarcane cultivars are unable to provide enough biomass due to their narrow genetic base and susceptibility to abiotic and biotic stresses. We have evaluated total of 23 hybrids derived from diverse genetic backgrounds of different Saccharum spp. and allied genera, one inbred and compared with commercial checks. Intergeneric hybrids (IGHs) KGS 99-100 and GU 04-432, produced significantly higher biomass (43.37 t ha-1 and 35.24 t ha-1, respectively) than commercial sugarcane have genes derived from Erianthus arundinaceus. Interspecific hybrids (ISHs) GU 07-3704 and 99-489, also produced significantly higher amounts of biomass (37.24 t ha-1 and 33.25 t ha-1, respectively) than commercial checks have genes from S. officinarum and S. spontaneum backgrounds. ISHs recorded significantly higher biomass yield, number of stalks and total dry matter percentage whereas, IGH group recorded significantly higher fibre percent. Furthermore, the clones resistant to red rot and sugarcane borers were identified. The estimated energy value for seven hybrid clones was found to be very high. Cluster analysis of genetic traits revealed two major clusters in traits improving biomass. Our study has revealed that the genetic diversity present in these hybrids could be used for improving biomass production and tolerance to abiotic and biotic stresses in cultivated sugarcanes.

A pediatric echocardiographic Z-score nomogram for a developing country: Indian pediatric echocardiography study - The Z-score.

BACKGROUND: Almost all presently available pediatric echocardiography Z-score nomograms are based on Western data. They may not be a suitable reference standard for assessing the sizes of cardiac structures of children from developing countries. OBJECTIVE: This study's objective was to collect normative data of 21 commonly measured cardiovascular structures using M-mode and two-dimensional echocardiography in Indian children aged between 4 and 15 years and to derive Z-score nomograms for each. SUBJECTS AND METHODS: The study was conducted at two centers in India - Ajmer, Rajasthan, and Mohali, Punjab. We studied a community-based sample involving healthy school going children. After excluding children with cardiovascular abnormalities on the screening echocardiogram, 746 children were included in the final analysis. Echocardiographic assessment was performed using a Philips iE33 system. RESULTS AND ANALYSIS: For each parameter measured, seven models were evaluated to assess the relationship of that parameter with the body surface area and the one with the best fit was used to plot the Z-score chart for that parameter. Z score charts were thus derived. CONCLUSIONS: The Z-score nomograms derived by this study may be better alternatives to the Western nomograms for use in India and other developing countries for preprocedural decision making in the pediatric population. However, they will require validation in large-scale studies before they can become clinically applicable.

Cedrus deodara: In vitro antileishmanial efficacy & immumomodulatory activity.

BACKGROUND & OBJECTIVES: The existing antileishmanial drugs for complete cure of visceral leishmaniasis (kala-azar) are limited. The available drugs are either toxic or less effective leading to disease relapse or conversion to post-kala-azar dermal leishmaniasis. Several herbal extracts have been shown to have antileishmanial activity, but a herbal drug may not always be safe. In the present study, the extract of Cedrus deodara leaves has been standardized and tested for immunomodulatory antileishmanial activities. METHODS: The extracts of C. deodara leaves with different solvents such as benzene, chloroform, ethyl acetate and methanol were made by soxhlation process. Solvents were removed under reduced pressure and temperature using rotary evaporator. The antileishmanial bioassay test was performed with in vitro maintained parasites. Immunomodulatory activity of different extracts was tested by flow cytometry. Standardization of the effective fraction was performed with Linalool as a marker compound through reverse-phase high-performance liquid chromatography. RESULTS: The extract with the use of benzene solvent showed strong antileishmanial activities within a dose 25-200 µg/ml culture with non-significant haemolytic activities and significant immunomodulant activities against the host cells. Linalool was found to be 1.29 per cent in the effective extract of C. deodara. INTERPRETATION & CONCLUSIONS: The antileishmanial activity of C. deodara, as assessed by bioassay testing on. LEISHMANIA DONOVANI: parasites and immunomodulatory effect of benzene extract of leaves on host cells indicated that it might be a potential new safe therapeutic target to cure the visceral leishmaniasis.

Identification of a diverse indole-2-carboxamides as a potent antileishmanial chemotypes.

A novel series of highly diverse indole-2-carboxamides was synthesized utilizing the isocyanide based multicomponent reaction (IMCR)-post modification approach and were identified as potential antileishmanial chemotype. Among the synthesized 18 analogues, 12 analogues exhibited better antileishmanial activity against intracellular amastigotes form of Leishmania donovani (IC50 values of 0.6-7.5 µM) as compared to standard drugs miltefosine and sodium stibogluconate. The compounds were also non-toxic towards Vero cells. Compounds 2b, 2m and 2p with significant in vitro activity were then evaluated for their in vivo efficacy following intraperitoneal route. These three compounds at a concentration of 50 mg/kg/day for 5 consecutive days showed 70.0, 63.5 and 63.4% inhibition of Leishmania amastigotes, respectively at day 7 post treatment in hamster model of visceral leishmaniasis.

Association of functional genetic variants of transcription factor Forkhead Box P3 and Nuclear Factor-κB with end-stage renal disease and renal allograft outcome.

BACKGROUND: The transcription factor FOXP3 and NF-κB regulates the expression of various genes that play an important role in the regulation of renal inflammation. We investigated the association of FOXP3 (rs2232365, rs3761548, rs5902434 and rs2294021) and NF-κB1 (rs28362491 and rs696) gene variants in susceptibility and prognosis of end stage renal disease (ESRD) and renal allograft outcome. METHODS: We genotyped four common polymorphisms of FOXP3 and two-tag SNPs of NF-κB1 genes in 350 ESRD cases and 350 controls. Single marker analysis and SNP-SNP interaction model (one to six way combinations) was used for determination of clinical outcome of ESRD and acute rejection episode (ARE). RESULTS: We observed significantly higher occurrence of mutant genotypes of tag-SNPs of FOXP3 namely; rs2232365 and rs3761548 along with NF-kB1 namely; rs28362491 and rs696 in ESRD and ARE cases, suggested a risk association for ESRD and ARE. Interestingly, multifactor dimension reduction analysis suggested an increased risks of nearly 6-folds for ESRD and 23-folds for ARE cases under the six factors model which consists of tag-SNPs of FOXP3 (rs2232365, rs3761548, rs5902434 and rs2294021) and NF-kB1 (rs28362491 and rs696). Kaplan-Meier survival analysis showed the lowest overall survival for mutant genotypes compared with wild and heterozygous genotypes of rs2232365 and rs3761548 tag SNPs of FOXP3 as well as NF-kB1 tag-SNPs rs28362491 and rs696 in renal allograft recipients. The crude and adjusted hazard ratios in univariate and multivariate Cox regression models showed almost 2-folds to 3-folds risk for overall survival against mutant genotypes of tag-SNPs of FOXP3 (rs2232365 and rs3761548) and NF-kB1 (rs28362491 and rs696) genes. CONCLUSIONS: These results suggest that variants of transcription factor FOXP3 and NF-kB1 might be associated with increased risk to the clinical outcome of ESRD and renal allograft survival.

Genetic variation in Micro-RNA genes of host genome affects clinical manifestation of symptomatic Human Cytomegalovirus infection.

BACKGROUND: Micro-RNAs are implicated in various physiological and pathologic processes. In this study, we tested whether Micro-RNA gene variants of host-genome affect clinical manifestation of symptomatic HCMV infection. METHODOLOGY: HCMV infection was detected by fluorescent PCR and immuno-histochemistry. The detection of genetic variants of four studied Micro-RNA tag-SNPs was done through PCR-RFLP assay and validated with DNA sequencing. RESULTS: We observed an increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for mutant genotype of rs2910164 (crude OR=3.11, p=0.009 and adjusted OR=3.25, p=0.007), rs11614913 (crude OR=3.20, p=0.006 and adjusted OR=3.48, p=0.004) and rs3746444 (crude OR=4.91, p=0.002 and adjusted OR=5.28, p=0.002) tag-SNPs. Interestingly, all the tag-SNPs that were significant after multiple comparisons at a FDR of 5% in symptomatic HCMV cases remained significant even after bootstrap analysis, providing internal validation to these results. Multifactor Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832, rs11614913 and rs3746444). CONCLUSIONS: These results suggest that Micro-RNA gene variants of host-genome may affect clinical manifestation of symptomatic HCMV infection.

Cytotoxic T-lymphocyte antigen 4 gene polymorphism influences the incidence of symptomatic human cytomegalovirus infection after renal transplantation.

BACKGROUND: The role of CTLA4 gene polymorphisms in T-cell-mediated immunity in association with human cytomegalovirus (HCMV) infection after transplantation is poorly understood. In the present study, we have made an attempt to investigate the impact of CTLA4 single nucleotide polymorphisms (SNPs) (rs231775, rs5742909, rs11571317, rs16840252, rs4553808, rs3087243) and dinucleotide (AT)n repeat polymorphism on the incidence of symptomatic HCMV infection (disease) among 270 renal allograft recipients. MATERIALS AND METHODS: Genotyping of CTLA4 SNPs was performed by a PCR, followed by a restriction fragment length polymorphism assay. The detection of the dinucleotide (AT)n repeat polymorphism was carried out by PCR-polyacrylamide gel electrophoresis. RESULTS: An almost three-fold increased risk was observed for the incidence of symptomatic HCMV infection in mutant genotype carriers of rs231775 and rs3087243 SNPs under additive and recessive models, respectively. The mutant haplotype carriers of six studied SNPs (rs231775, rs5742909, rs11571317, rs16840252, rs4553808 and rs3087243) showed an almost two-fold higher risk for symptomatic HCMV cases, whereas wild-type haplotype combinations of these six SNPs showed a protective effect. Subsequently, no correlation was observed in the promoter region SNPs of CTLA4, namely, rs5742909, rs11571317, rs16840252 and rs4553808 in symptomatic HCMV cases at the genotypic/allelic level. Survival analysis showed that the mutant genotypes of rs231775 and rs3087243 SNPs were associated with the lowest HCMV disease-free survival compared with heterozygous and wild genotypes. The crude and adjusted hazard ratios showed an almost three-fold and 2.5-fold increased risk in univariate and multivariate Cox regression models, respectively, for HCMV disease-free survival against mutant genotypes of rs231775 and rs3087243 SNPs. CTLA4 dinucleotide (AT)n repeat analysis showed that the smaller allele (102 bp) was associated with a protective effect, whereas the longer (110 and 116 bp) alleles showed a susceptible effect for symptomatic HCMV cases. CONCLUSION: These results suggested that CTLA4 variants might be involved in the clinical manifestation of HCMV diseases.

Genetic variants of MicroRNA-related genes in susceptibility and prognosis of end-stage renal disease and renal allograft outcome among north Indians.

BACKGROUND AND AIM: MicroRNAs are important molecules of the innate and adaptive immune system, which may play an important role in maintaining normal immune homeostasis. The aim of this study was to investigate the impact of MIR146A C>G (rs2910164), MIR149 T>C (rs2292832), MIR196A2 T>C (rs11614913), and MIR499A A>G (rs3746444) single nucleotide polymorphisms (SNPs) among end-stage renal disease (ESRD) and acute allograft rejection (AR) cases. MATERIALS AND METHODS: Genotyping of MicroRNA SNPs was performed using a PCR, followed by restriction fragment length polymorphism in 350 ESRD patients and 350 age-matched, sex-matched, and ethnically matched controls. RESULTS: We observed an increased risk of almost two-fold for ESRD and three-fold for AR cases under univariate and multivariate models for mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs. Subsequently, no susceptible/protective effect was observed for rs2292832 SNP with ESRD and AR cases. Interestingly, all the SNPs that were significant after multiple comparisons in ESRD and AR cases remained significant in the bootstrap analysis, providing internal validation to our initial observations. Survival analysis showed that the mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs were associated with the lowest overall survival compared with heterozygous and wild genotypes among renal allograft recipients. The crude and adjusted hazard ratios in univariate and multivariate Cox regression models showed an almost two-fold increased risk for overall survival against mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs in renal allograft recipients. CONCLUSION: These results suggest that the variants of MicroRNA SNPs, namely, rs2910164, rs11614913, and rs3746444, might be involved in susceptibility to ESRD and AR.

HLA-G gene expression influenced at allelic level in association with end stage renal disease and acute allograft rejection.

BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical major-histocompatibility complex class-I molecule associated with immunosuppressive function. We have evaluated the impact of HLA-G allele associated with untranslated-region (UTR)-haplotype in end stage renal disease (ESRD) and acute allograft rejection (AR) cases. The mRNA levels of different HLA-G isoforms were evaluated in ESRD and AR cases. Subsequently, the total HLA-G mRNA levels and protein concentration were evaluated against its UTR-haplotype among ESRD and AR cases. METHODOLOGY: Sequence based typing of the promoter region was carried-out to evaluate the impact of HLA-G haplotype in 350 ESRD cases and 300 controls. HLA-G gene expression was evaluated at the transcriptional level using semi-quantitative and quantitative PCR, whereas protein concentration was determined by ELISA among both cases and control. RESULTS: Increased risk was observed for G*01:01:01:03, G*01:01:02, G*01:06 and G*01:05:N haplotypes while G*01:01:01:01 and G*01:04:01 haplotypes showed a protective effect in ESRD and AR cases. Higher level of soluble HLA-G isoforms (G5 and G6) was observed among ESRD cases. Reduced levels of soluble isoform (G5) and increased levels of membrane bound (G1 and G3) isoforms were found among AR cases, revealing risk association. Decreased HLA-G expression was observed at both mRNA and protein level for G*01:01:01:03 and G*01:05:N haplotypes in ESRD and AR cases. CONCLUSIONS: These results suggest that the variation in the expression profile of membrane bound and soluble isoforms may modulate the risk for ESRD and AR. UTR-haplotypes appear to be involved in different HLA-G expression patterns at transcriptional and translational levels.

Base mediated 7-exo-dig intramolecular cyclization of Ugi-propargyl precursors: a highly efficient and regioselective synthetic approach toward diverse 1,4-benzoxazepine-5(2H)-ones.

A metal-free facile and efficient two-step synthetic protocol for the preparation of 1,4-benzoxazepine-5(2H)-one derivatives has been developed. The protocol involves Ugi reaction followed by K2CO3 mediated highly regioselective 7-exo-dig intramolecular cyclization of less-nucleophilic oxygen with the pendant alkyne moiety of an Ugi-propargyl precursor to afford the 1,4-benzoxazepine-5(2H)-one derivatives in good to excellent yields.

Presence of accessory penis, colonic duplication and several other congenital anomalies in a child: a very rare association.

An accessory penis is a very rare anomaly. Only five cases have been reported thus far to our knowledge. We present the case of a child aged 2 years and 10 months who had a penis-like structure (containing phallus and glans) attached to the right buttock. Associated anomalies were a non-communicating type of colonic duplication, a paramedian stenosed anal opening, a horse-shoe kidney, posterior urethral valves, scoliosis of the lumbo-sacral spine, polydactyly and equino-varus deformity of the right foot. As far as we can tell, this is the first report of an accessory penis associated with colonic duplication and other congenital anomalies.

Association of CTLA-4 gene polymorphism with end-stage renal disease and renal allograft outcome.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is upregulated in effector-T-cells after activation that may alter signal transduction and subsequently cytokine production. The present study was designed to investigate the impact of CTLA-4+49 A>G (rs231775), -318 C>T (rs5742909), -658 C>T (rs11571317), -1147 C>T (rs16840252), -1661 A>G (rs4553808), +6230 A>G (rs3087243) SNPs, and microsatellite (AT)n repeat polymorphism among end-stage renal disease (ESRD), acute allograft rejection (AR), and delayed graft function (DGF) cases. In this regard, 350 ESRD patients and 350 controls were included. Polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis method was used for genotyping of CTLA-4 SNPs, while PCR-polyacrylamide gel electrophoresis method was adopted for studying CTLA4 (AT)n polymorphism. The mutant genotype GG of CTLA-4+49A>G,+6230 A>G, and longer alleles of (AT)n repeats polymorphisms were risk associated with ESRD, AR, and DGF cases. The distribution of haplotype+49G:+6230G and GCTTGG (constructed by using 6 studied SNPs) showed risk association for ESRD, DGF, and AR cases. Further, linkage analysis demonstrated strong to moderate linkage disequilibrium in our study populations. The meta-analysis also revealed risk associations for AR cases against GG genotype of CTLA-4+49A>G SNP, while CTLA-4 -318C>T polymorphism showed no correlation against TT genotype among AR cases. Subsequently, no correlation was established against the CTLA-4 -318C>T, -658 C>T, -1147 C>T, and -1661 A>G SNPs in the promoter region. Survival analysis revealed risk associations against GG genotype of CTLA-4+49A>G, +6230 A>G SNP's with overall survival (OS), and higher hazard for the OS. These results suggested that CTLA-4 variants might be involved in susceptibility to ESRD, AR, and DGF.