Prevalence of virulent Candida spp. in complicated urinary tract infection of nephrolithiatic patients from surgical units of tertiary care hospitals Islamabad.

Candida species are the commensal organisms of human mucosa and opportunistically cause the diseases in susceptible persons. This study aimed to determine the prevalence and virulence of different Candida spp. among nephrolithiatic patients and their association with complicated UTI (cUTI). A total of 164 urine samples were collected from surgical units of two tertiary care hospitals (Poly Clinic and Pakistan Institute of Medical Sciences Hospital, Islamabad). From 74 kidney stone patients, 77 isolates of Candida spp. were confirmed through standard microbiological and molecular characterization. C. albicans was the predominant species with 51 isolates (66.2%) followed by 26 (33.8%) of C. non-albicans. The nephrolithiatic patients suffering from cUTI were more prone to be infected with Candida (P=0.047). Among all isolates, 83% (64) of the Candida isolates were biofilm formers, 80% (60) showed the esterase production and 64.9% (50) showed phospholipase production. Candida isolates positive for various virulence factors were more prevalently isolated from both catheterized and recurrent UTI patients. Among Candida spp., 16.9% (13) isolates showed resistance to fluconazole and 19.5% (15) against voriconazole and 11 isolates were resistant for both tested antifungals. Candida isolated from cUTI cases showed comparatively enhanced virulence attributes and antifungal resistance, suggesting that these factors might have role in development of cUTI in nephrolithiatic patients. Hence, this work highlights the high prevalence of both C. albicans and non albicans spp. in nephrolithiatic patients. So, there is need to administer evidence based antifungal therapy rather than empirical therapy to reduce the cUTI in nephrolithiatic patients.

Novel SYK gene variations and changes in binding sites of miRs in breast cancer patients.

BACKGROUND: Spleen Tyrosine Kinase (SYK) belongs to non-receptor tyrosine Kinase family, which normally expresses in epithelial breast tissues and acts as a tumor suppressor gene. OBJECTIVE: Analysis of mutations in the SYK gene and deregulation of SYK transcripts by miRNA in breast cancer was studied. METHODS: All exons and exon/intron boundaries of SYK gene were amplified and sequenced in blood samples of 207 breast cancer cases and 200 matched controls using PCR-single stranded conformational polymorphism method. RESULTS: Sequence analysis revealed 10 novel mutations in breast cancer patients. Among these 6 mutations (Ala 161Pro, His162Tyr, Phe191Tyr, Val 535Gly, Ser 556lIe and Lys536Gln) were found in exonic region and 4 (26249 T>A, 63941 G>A, 63981G>C and 86548T>A) were found in intronic region. All of these mutations are associated with ∼ 5 folds (p< 0.0001) increase in breast cancer risk in present study cohort. Regulation of SYK transcripts by miRNA was also analyzed using in silico bioinformatics tools, exon 6's mutation (Phe191Tyr) was found to have altered interaction with miR-873. CONCLUSION: Overall novel mutations in SYK gene and in silico analysis revealed that these mutations are crucial and might be responsible for altered expression of SYK.