BackgroundInterferon regulatory factor (IRF)-5 is a transcription factor involved in type I interferon signaling whose germ line variants have been associated with autoimmune pathogenesis. Since relationships have been observed between development of autoimmunity and responsiveness of melanoma to several types of immunotherapy, we tested whether polymorphisms of IRF5 are associated with responsiveness of melanoma to adoptive therapy with tumor infiltrating lymphocytes (TILs).Methods140 TILs were genotyped for four single nucleotide polymorphisms (rs10954213, rs11770589, rs6953165, rs2004640) and one insertion-deletion in the IRF5 gene by sequencing. Gene-expression profile of the TILs, 112 parental melanoma metastases (MM) and 9 cell lines derived from some metastases were assessed by Affymetrix Human Gene ST 1.0 array.ResultsLack of A allele in rs10954213 (G > A) was associated with non-response (p < 0.005). Other polymorphisms in strong linkage disequilibrium with rs10954213 demonstrated similar trends. Genes differentially expressed in vitro between cell lines carrying or not the A allele could be applied to the transcriptional profile of 112 melanoma metastases to predict their responsiveness to therapy, suggesting that IRF5 genotype may influence immune responsiveness by affecting the intrinsic biology of melanoma.ConclusionsThis study is the first to analyze associations between melanoma immune responsiveness and IRF5 polymorphism. The results support a common genetic basis which may underline the development of autoimmunity and melanoma immune responsiveness.

Objectives Recent genome-wide association studies (GWAS) have identified more than 40 common sequence variants associated with type 2 diabetes (T2D). However, the results are not always the same in populations with differing genetic backgrounds. We evaluated a hypothesis that a North Asian population living in a geographic area with unusually harsh environmental conditions developed unique genetic risks. Methods We performed a population-based association study with 21 single-nucleotide polymorphisms (SNPs) in 9 genes selected according to the results of GWAS conducted in other populations. The study participants included 393 full-heritage Mongolian individuals, 177 diagnosed with T2D and 216 matched controls. Genotyping was performed by TaqMan methodology. Results The strongest association was detected with SNPs located within the potassium-channel coding KCNQ1 (highest OR=1.92; P=3.4×10−5) and ABCC8 (OR=1.79; P=5×10−4) genes. Genetic variants identified as strongly influencing the risk of T2D in other populations such as those in KCNJ11 or TCF7L2 genes did not show statistically significant association in Mongolia. Conclusions The strongest T2D risk-associated SNPs in Mongolians are located within 2 of 3 tested potassium-channel coding genes; accumulated variations in these genes may be related to environmental exposure to extreme cold.

Poorly controlled patients with type 2 diabetes and people without diabetes of over 55 years of age are likely to be at a higher risk of developing hyperferritinaemia. Thus, regular assessments of serum ferritin might be important for those who are at risk of hyperferritnaemia for prevention and an early intervention.

HRAS belongs to the RAS genes superfamily. RAS genes are important players in several human tumors and the single-nucleotide polymorphism rs12628 has been shown to contribute to the risk of bladder, colon, gastrointestinal, oral, and thyroid carcinoma. We hypothesized that this SNP may affect the risk of cutaneous melanoma as well. HRAS gene contains a polymorphic region (rs112587690), a repeated hexanucleotide -GGGCCT- located in intron 1. Three alleles of this region, P1, P2, and P3, have been identified that contain two, three, and four repeats of the hexanucleotide, respectively. We investigated the clinical impact of these polymorphisms in a case–control study. A total of 141 melanoma patients and 118 healthy donors from the North America Caucasian population were screened for rs12628 and rs112587690 polymorphisms. Genotypes were assessed by capillary sequencing or fragment analysis, respectively, and rs12628 CC and rs112587690 P1P1 genotypes significantly associated with increased melanoma risk (OR = 3.83, p = 0.003; OR = 11.3, p = 0.033, respectively), while rs112587690 P1P3 frequency resulted significantly higher in the control group (OR = 0.5, p = 0.017). These results suggest that rs12628 C homozygosis may be considered a potential risk factor for melanoma development in the North American population possibly through the linkage to rs112587690.

was 21% at 10 years and according to the Karnofsky index, most of our patients require ongoing help and frequent medical care. The average duration of dialysis was 47.3 months (2-192 months). 44 patients (81%) had a rhythm of 3 sessions per week, while the remaining 19% were dialyzed twice a week with an average duration of the session of 3.7 hours. Most of our patients (82%) had an arteriovenous fistula (AVF), 5 patients (9.4%) were dialyzed via a femoral valve and 5 patients via a jugular catheter. Most of our patients were anemic with an average hemoglobin level of 8.9 g / dl, hypocalcemia was present in 23 patients (43.3%), hyperphosphatemia in 16 patients (30.1%) and secondary hyperparathyroidism in 22 patients (41.5%). The main complications in hemodialysis were stroke in 3 patients (5.6%), pericarditis in 4 patients (7.5%) and coronary insufficiency in 8 patients (15.1%). Regarding cognitive disorders, 2 patients (3.7%) had dementia, 6 patients (11.3%) had depression, 11 patients (20.7%) had anxiety, and 32 patients (60.3%) had insomnia. Two cases of death were noted whose etiology was a rupture of a false aneurysm in one patient and wet gangrene in the other patient. Conclusions: The elderly are a population of frail patients with high comorbidity and autonomic disorders. Chronic hemodialysis treatment is a heavy treatment that requires regular monitoring to avoid particular complications of the elderly.Introduction: Current literature suggests the arteriovenous fistula (AVF) to be the preferred type of vascular access for hemodialysis. However, AVFs have significant and potentially deleterious effects on cardiac functions particularly in the setting of preexisting heart disease. The aim of this study is to compare the clinical and echocardiographic evolution after creation of a proximal AVF and a radial AVF. Methods: We conducted a retrospective descriptive study including all chronic hemodialysis patients through AVF. Group 1 (G1) included patients with proximal AVF and group 2 (G2) patients with radial AVF. Data collected included demographics, Clinical Status, vascular access type, and metabolic parameters. Data were entered and analyzed using SPSS software. Chi-squared test with a level of significance of 0.05 was used for the qualitative variables. Results: Twenty-four patients were collected in G1 and the average age was 55 years. G2 included 13 patients with a mean age of 44 years. Systolic blood pressure decreased after AVF creation in both groups (G1: 62.5%, G2: 45%, NS). A dyspnea was noted in 70% of cases of G1 and 38.4% of cases of G2 (NS). The interventricular septum was thickened in 20.8% of cases of G1 and 38.4% of G2 (NS). Left ventricular (LV) dilatation was observed in both groups with LV diastolic telegram diameter increase of 58% in G1 versus 10% in G2 (p ¼ 0.04). A decrease in LV ejection fraction was found in 62.5% in G1 and 46.1% in G2 (p ¼ 0.066). The major cardiac complications in G1 were acute coronary syndrome in 5 patients and atrial fibrillation in 4 cases after an average of...