Multidrug resistant A. baumannii has emerged as an important and problematic human pathogen as it is the causative agent of several types of infections especially in neonates and immunocompromised patients because they have least capacity to fight against infections. Carbapenems are used as last resort antibiotics for treating these infections but currently resistance against carbapenems due to MBL production is on the rise. The objective of this study was to determine the frequency of antibiotic resistance in A. baumannii and also to compare the efficacy of combined disk test and double disk synergy test for detection of metallo-beta-lactamases. A total of 112 A. baumannii were identified from various clinical samples and antibiotic susceptibility profile was determined by Kirby-Bauer Disk Diffusion method. Out of 112, 66 (58.9%) isolates were resistant to both imipenem and meropenem (OXOID). These resistant isolates were tested for carbapenemase production, and 55 (83.3%) were carbapenemase producers by Modified Hodge Test. These isolates were further tested for MBL production by combined disk test and double disk synergy test. Out of 66, 49 isolates were positive by both methods, CDT and DDST, and only one isolate was detected as negative (with kappa value = 0.038). All MBL producing strains showed remarkable resistance to cephalosporins, fluoroquinolones, aminoglycosides, and piperacillin/tazobactam (OXOID). The antibiotic resistance was very high in A. baumannii which were isolated from children in Pakistan specially attending a nephrology unit.

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Introduction: Genome-wide association studies (GWAS) have identified numerous stroke-associated SNPs. To understand how SNPs affect gene expression related to increased stroke risk, we studied epigenetic landscapes surrounding 26 common, validated stroke-associated loci. Methods: We mapped the SNPs to linkage disequilibrium (LD) blocks and examined H3K27ac, H3K4me1, H3K9ac, and H3K4me3 histone marks and transcription-factor binding-sites in pathologically relevant cell types (hematopoietic and vascular cells). Hi-C data were used to identify topologically associated domains (TADs) encompassing the LD blocks and overlapping genes. Results: Fibroblasts, smooth muscle, and endothelial cells showed significant enrichment for enhancer-associated marks within stroke-associated LD blocks. Genes within encompassing TADs reflected vessel homeostasis, cellular turnover, and enzymatic activity. Conclusions: Stroke-associated genetic variants confer risk predominantly through vascular cells rather than hematopoietic cell types.

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The present study investigated the relationship of STAT4 single nucleotide polymorphisms (SNPs) rs7574685, rs10181656, and rs3821236 with T1D susceptibility visiting tertiary care hospital in Lahore, Punjab, Pakistan. One hundred and fifty-five T1D patients and one hundred and five healthy individuals were enrolled. An expert endocrinologist collected the clinical data of T1D patients. The genotyping of three potential STAT4 SNPs was performed through Tetra ARMS-PCR assay. The relationship between SNPs and T1D susceptibility under several genetic models, including dominant, recessive, and codominant models, was assessed by regression analysis. All clinical features of T1D demonstrate a significant difference from control groups (P<0.01) except blindness. The characteristic biochemical analysis determined that participants with T1D had significantly higher fasting blood glucose levels and glycated hemoglobin (HbA1c) levels than the control group (P<0.01). Genetic analysis of rs7574685 depicts GT genotype was found to be the risk allele for the development of T1D when compared to the control group. For rs10181656 and rs3821236, the GC genotype and GA genotype were observed to be the risk alleles in the T1D cases as compared to the control group (P=0.04, P<0.01, respectively). Genetic models showed that the STAT4 GG genotype of rs7574685 in the dominant model (OR=1.73, 95% CI=1.05-2.86), GC genotype of rs10181656 in the codominant model (OR=2.079, 95 % CI=1.16-3.71), and AA genotype of rs3821236 showed significant risk association with T1D (OR=3.486, 95% CI=1.72-7.03). It is concluded that the risk of T1D is highly correlated with the STAT4 variants of rs7574685 and rs10181656 among children of the Pakistani population.