Frequency of Biopsy and Tumor Grade Before vs After Introduction of Prostate Magnetic Resonance Imaging.

Importance: In randomized clinical trials (RCTs), magnetic resonance imaging (MRI) before prostate biopsy has been associated with fewer biopsies, decreased detection of Gleason score 6 cancers, and increased detection of Gleason score 7 or higher cancers. Objective: To study whether MRI of the prostate before the decision to biopsy is associated with biopsy frequency and distribution of Gleason score in clinical practice. Design, Setting, and Participants: This is a retrospective, population-based cohort study of men in Jönköping Region, Sweden. Men with prostate-specific antigen (PSA) level measured between November 2011 and 2020 were monitored until January 31, 2021. Men with known prostate cancer were excluded. Data analysis was performed from July to December 2022. Exposures: Data on repeated PSA measures, prostate biopsies, and MRI prostate were extracted from health care records, and cancer characteristics were obtained from The National Prostate Cancer Register. Main Outcomes and Measures: The proportions of men who underwent prostate biopsy and risk of Gleason score 6 or Gleason score 7 or higher cancer and negative biopsy before and after introduction of MRI were calculated. Results: In this cohort study of 23 802 men (mean [SD] age, 60.8 [13.6] years) who underwent PSA testing, when the use of MRI increased, fewer biopsies were performed (adjusted odds ratio [OR], 0.84; 95% CI, 0.72-0.97) and the odds of detecting Gleason score 6 cancer decreased (OR, 0.47; 95% CI, 0.33-0.64), whereas the odds of detecting Gleason score 7 or higher cancer increased (OR, 1.24; 95% CI, 1.02-1.50). Conclusions and Relevance: In this study, the introduction of MRI to clinical practice was associated with a decreased proportion of men who underwent a biopsy and decreased detection of Gleason score 6 cancer but increased detection of Gleason score 7 or higher cancer. These clinical data support the use of prostate MRI before biopsy in an effort to avoid unnecessary biopsies.

Elucidating novel antibacterial compounds from the NPASS database against the FimH lectin domain for the treatment of urinary tract infections: an in-silico study.

The increase in multidrug-resistant pathogens in urinary tract infections (UTIs) among communities and hospitals threatens our ability to treat these common pathogens. Uropathogenic Escherichia coli (UPEC) strains are the most frequent uropathies linked to the development of UTIs. This work aims to introduce bioactive natural products via virtual screening of small molecules from a public database to prevent biofilm formation by inhibiting FimH, a type 1 fimbriae that plays a crucial role in UPEC pathogenicity. A total of 30926 small molecules from the NPASS database were subjected to screening via molecular docking. Followed by performing in silico ADME studies, seven molecules showed promising docking results ranging from -6.8 to -8.7 kcal/mol. As a result of the docking score findings, 100 ns Molecular dynamics (MD) simulations were performed. Based on MM-PBSA analysis, NPC313334 ligand showed high binding affinity -42 and stability with the binding pocket of FimH protein during molecular dynamic simulations. DFT calculations were also performed on the ligands to calculate the HOMO-LUMO energies of the compounds in order to an idea about their structure and reactivity. This research suggests that NPC313334 may be a possible antibacterial drug candidate that targets FimH to reduce the number of UPEC-related urinary tract infections.Communicated by Ramaswamy H. Sarma.

Pharmacogenetic Effect of Thiopurine Methyl Transferase (TPMT) Gene Expression and Serum TNF on the Imuran Response in Ulcerative Colitis (UC) Iraqi Patients.

Background: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), exerts its impact on both rectal and colonic mucosa, with a growing incidence. This study aims to explore the pharmacogenetic influence of thiopurine methyl transferase (TPMT) gene expression and serum tumor necrosis factor (TNF) levels on the response to Imuran in Iraqi patients with UC. Methods: Seventy individuals with chronic UC and 30 healthy controls were enrolled in this investigation. RNA extraction using the triazole method and enzyme-linked immunosorbent assay (ELISA) for TNF measurement were employed. Patients, aged 15-50 years, underwent Imuran treatment. Results: Diverse responses to Imuran were observed among patients, with TPMT gene expression levels below 1 in 35 patients leading to side effects, while the remaining 35 patients exhibited positive responses with TPMT gene expression exceeding 1. Patients with varying degrees of severe, moderate, and mild UC associated with TNF showed a significant correlation with Imuran non-response. Conclusions: A distinct correlation was identified between TPMT gene expression and Imuran therapy outcomes in UC patients. Further investigation is warranted to elucidate the underlying mechanism, positioning the TPMT gene as a potential therapeutic target for mitigating the impact of UC.

Pharmacokinetic Effect of MDR Gene Polymorphism rs2032582 on the Therapeutic Response in Iraqi Patients with Acute Myeloid Leukemia.

BACKGROUND: The main problem in treatment of leukemia patients is the chemotherapy resistance which is a main concern in recent years. The cause of chemotherapy drug resistance is related to MDR gene which is located on chromosome 7 (7q21-31) and it is mainly connected with energy-dependent efflux (P-glycoprotein). This study was conducted to assess the correlation between MDR polymorphism and chemotherapy efficiency with Vincristine in a sample of Iraqi Acute Myeloid Leukemia (AML) patients. METHODS: The blood sample of 200 AML patients and 200 controls were collected and the frequency of rs2032582 was calculated through sequencing and then the role of different genetic patterns was evaluated on cancer cells by MTT assay. RESULTS: The results indicate that GG and TT genotypes (20 and 20.5% from total patients count) are more frequent in Iraqi AML patients than other genetic patterns in MDR gene and also the genotype TA is more sensitive to Vincristine chemotherapy than other genotypes. CONCLUSION: It seems that genetic pattern is the main factor in determination of chemotherapy of AML patients, and patients should not undergo chemotherapy with such drugs, especially Vincristine.

Association study of two single nucleotide polymorphisms rs10757278 and rs1333049 with atherosclerosis, a case-control study from Iraq.

Atherosclerosis is one of the most important coronary artery disease (CAD) caused by lipid accumulation, hypertension, smoking, and many other factors such as environmental and genetic factors. It has been recorded that genetic variations in rs10757278 and rs1333049 are correlated with CAD. In the present study, 100 blood samples were collected (50 CAD patients and 50 appeared to be healthy controls), who referred to Ibn-Albytar general hospital/in Bagdad city for heart disease from February to March 2019. Genotyping for two SNPs rs10757278 and rs1333049, were done by Tetra ARMS method. For the rs10757278 polymorphism, the GG genotype verses to AA genotype was significantly associated with the risk of CAD (OR=5.16, 95% CI:1.02-26.0, P=0.047). For the rs10757278 polymorphism, there was no significant associatin between genotypes and the susceptibiulity to CAD. In the present study, the rs10757278 polymorphism showed an association with CAD.