Small molecule inhibitor of TLR4 inhibits ovarian cancer cell proliferation: new insight into the anticancer effect of TAK-242 (Resatorvid)

Cancer Chemotherapy and Pharmacology - Despite all advances in the treatment of ovarian cancer (OC), it remains the most lethal gynecological malignancy worldwide. There are growing amounts of...     

Improving patient flow at a family health clinic

This paper presents an analysis of a residency primary care clinic whose majority of patients are underserved. The clinic is operated by the health system for Bexar County and staffed primarily with physicians in a three-year Family Medicine residency program at The University of Texas School of Medicine in San Antonio. The objective of the study was to obtain a better understanding of patient flow through the clinic and to investigate changes to current scheduling rules and operating procedures. Discrete event simulation was used to establish a baseline and to evaluate a variety of scenarios associated with appointment scheduling and managing early and late arrivals. The first steps in developing the model were to map the administrative and diagnostic processes and to collect time-stamped data and fit probability distributions to each. In conjunction with the initialization and validation steps, various regressions were performed to determine if any relationships existed between individual providers and patient types, length of stay, and the difference between discharge time and appointment time. The latter two statistics along with resource utilization and closing time were the primary metrics used to evaluate system performance.The results showed that up to an 8.5 % reduction in patient length of stay is achievable without noticeably affecting the other metrics by carefully adjusting appointment times. Reducing the no-show rate from its current value of 21.8 % or overbooking, however, is likely to overwhelm the system’s resources and lead to excessive congestion and overtime. Another major finding was that the providers are the limiting factor in improving patient flow. With an average utilization rate above 90 % there is little prospect in shortening the total patient time in the clinic without reducing the providers’ average assessment time. Finally, several suggestions are offered to ensure fairness when dealing with out-of-order arrivals.     

Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and environmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal individuals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL-1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42–0.95; P < 0.05 relative to reference genotype and OR = 0.62, CI = 0.42–0.93; P < 0.05 relative to homozygous genotypes). For all other studied alleles and genotypes, there were no significant differences concerning genotype frequencies between patients and controls. A significant increase in IL-1RN rs315952 T allele frequency was noted in patients with a hematologic manifestation (OR = 1.75; 95 % CI = 1.07–2.84; P = 0.033). Polymorphism in IL-1RN rs315952 was significantly associated with SLE in Iranian patients, rs315952CT genotype being a protective factor. We found that IL-1RN rs315952 T allele frequency was significantly higher in patients with hematologic manifestations. Variation at this locus may affect IL-1 receptor antagonist activity, supporting the hypothesis that altered or imbalanced IL1 production may affect the risk of developing SLE.     

Upregulation of KAT2B and ESCO2 gene expression level in patients with rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) is an autoimmune condition that causes progressive inflammation. It seems that alternations in epigenetic modifications contribute to RA...     

Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis

Genetic factors have a great role in the pathogenesis of autoimmune diseases by cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs) are cell surface proteins on NK cells whose association with major histocompatibility complex-I regulates their killing function. The aim of this study was to provide information on the possible association between KIR and human leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian population. A total of 279 systemic sclerosis patients and 451 healthy controls were enrolled in this case-control study in order to determine the presence or absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by polymerase chain reaction using the specific sequence primer method (PCR-SSP). Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4 genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-gene interactions were also analyzed, and significant confounding effects were seen between involved genes in these two combinations: “KIR3DL1; HLA-BW4-Thr80” and “KIR3DL1 -HLA-BW4-A1.” None of single KIR genes showed significant effect on the risk of SSc. We conclude that there is an important relationship between KIR genes and their HLA ligands with incidence rate of systemic sclerosis in Iranian population. The powerful role of a number of discovered KIR/HLA compounds such as activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of the interplay between activating or inhibitory KIR genes with HLA ligands as a critical index of systemic sclerosis predisposition.