The interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappaB) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR=4.4, 95% CI=1.5 to 12.6, P=0.007). Functional consequences of the C>T substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (P<0.001) but no repression by the variant allele in any cell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappaB activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development.

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Success rate in human pregnancies is believed to be very low and sex-specific mechanisms may operate in prenatal loss. Assuming a sex-differential in prenatal loss exists, we examined genetic markers in biologically plausible targets in the HLA complex, other immune system-related and iron-regulatory genes in 388 healthy newborns from Wales (UK) using one sex as a control group for the other. Genotyping of 333 single nucleotide polymorphisms (SNPs) from 107 genes was achieved mainly by TaqMan assays. Twenty-two of autosomal SNPs showed frequency differences between 187 male and 201 female newborns either individually or as part of a haplotype. Of these, six markers (RXRB rs2076310, HLA complex haplotype HLA-DQA1 rs1142316-HLA-DRA rs7192-HSPA1B rs1061581, HIST1H1T rs198844, IFNG rs2069727, NKG2D rs10772266 and IRF4 heterozygosity) showed statistically robust differences between male and female newborns and multivariable modeling confirmed their independence. There were fewer males homozygote for combined wildtype genotypes of LIF rs929271, TP53 rs1042522 and MDM2 rs2279744 compared with females [OR = 0.3, 95% confidence interval (CI) = 0.1-0.8; P < 0.01] although these SNPs did not show any association individually. It is unlikely that SNPs have clinical utility as single markers in any trait with complex etiology but polygenic predictive models remain a possibility. If their validity is confirmed in larger studies of different populations and functional mechanisms of these preliminary associations are elucidated, these markers from the HLA complex, NKG2D region and cytokines may cumulatively have sufficient predictive value for susceptibility to prenatal selection in each sex.

The study aimed at determining 5-year incidence and prediction nomogram for new-onset type 2 diabetes (T2D) in a middle-aged population in Vietnam. Methods:A population-based prospective study was designed to collect socioeconomic, anthropometric, lifestyle and clinical data. Five-year T2D incidence was estimated and adjusted for age and sex. Hazard ratio (HR) for T2D was investigated using discrete-time proportional hazards model. T2D prediction model entering the most significant risk factors was developed using the multivariable logistic-regression algorithm. The corresponding prediction nomogram was constructed and checked for discrimination, calibration and clinical usefulness. F I G U R E 2 (a) The calibration curve analysis for nomogram of prediction model a . The calibration curve plots the predicted probability by nomogram of diabetes versus actual probability in the entire sample. Classification of the predicted values: fit calibration: 0.03−0.45; overestimated: >0.45. The dotted 45° line denotes ideal agreement between predicted and actual diabetes. (b) The decision curve analysis for the clinical usefulness of the nomogram a . The vertical axis indicates the standardized net benefit. The horizon axis shows the threshold probability for diabetes. The black line and the red line respectively present the net benefit when no participant and all participants are considered to develop type 2 diabetes. The decision curve (blue line) analysis shows a positive net benefit of the nomogram when the predicted probability thresholds between 0.03 and 0.36. a Using bootstrap resampling (times = 1000).

Background: The transversus abdominis plane block (TAP block), a regional block, provides effective analgesia after lower abdominal surgeries. The objective of this study was to assess whether transversus abdominis plane block is effective as part of multimodal pain management following Cesarean section. Materials and Method: Totally, 60 ASA I and II parturients for Cesarean section via Pfannenstiel incision under spinal anesthesia were randomly allocated to either the TAP block group or the control. The TAP block group received a landmark-orientated, bilateral TAP block with 0.25% levobupivacain 17,5ml each side in the triangle of Petit. Postoperative pain treatment followed the same protocole for both groups with 1gram paracetamol intravenously and received patrient-controlled analgesia with intravenous morphine. The time to first request of analgesic, morphine consumption, visual analogue scale (VAS) pain scores and side effects were scored at 2, 4, 6, 8, 12 h postoperatively. Results: The time to first request of analgesic was longer, morphine consumption was lower in TAP group than in the control (p < 0.05). Visual analogue scale (VAS) pain scores at rest and on mouvement were similar in two groups at 2h, but lower in TAP group from 4h (p < 0.05). No severe adverse effects were detected in two groups. Conclusion: TAP block prolonged the time to fisrt request of analgesic and reduced morphine consumption, the VAS pain scores significantly both at rest and on mouvement. Therefore, TAP block is feasible and effective as part of a multimodal analgesia regimen after Caesarean section. Key words: Caesarean section, multimodal pain management, transversus abdominis plane block