Insulin-like factor 3 (INSL3) is a member of the relaxin-insulin family, and it is expressed in pre- and postnatal Leydig cells of the testis. This peptide affects testicular descent during embryonic development, and mutations in INSL3 gene or its receptor LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8)/GREAT (G protein-coupled receptor affecting testicular descent) cause cryptorchidism in humans. The expression of LGR8/GREAT in different tissues and the production of INSL3 also by adult-type Leydig cells suggest additional roles of this hormonal system in adulthood. In this preliminary report we performed the first analysis in humans of INSL3 using a novel RIA kit to measure INSL3 concentrations in serum of normal men and with different testicular pathologies. The results show that INSL3 is circulating in adult men, and it is almost exclusively of testicular origin. Subjects with severe testicular damage, such as men with severe infertility, produce low amount of INSL3, and the concentrations of this hormone seem to reflect the functional status of the Leydig cells. In particular, INSL3 concentrations may be an even more sensitive marker of Leydig cell function than testosterone itself. Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to LH in a manner similar to that of the LH-testosterone axis.

Coagulation factor V (FV), present in plasma and platelets, is indispensable to thrombin formation, yet patients with undetectable plasma FV seldom experience major bleeding. We used thrombin generation assays to explore the role of platelet

The Spalt-Like Transcription Factor 4 (SALL4) oncogene plays a central function in embryo-fetal development and is absent in differentiated tissues. Evidence suggests that it can be reactivated in several cancers worsening the prognosis. We aimed at investigating the risk associated with SALL4 reactivation for all-cause mortality and recurrence in cancer using the current literature. A PubMed and SCOPUS search until 1st September 2016 was performed, focusing on perspective studies reporting prognostic parameters in cancer data. In addition, 17 datasets of different cancer types from The Cancer Genome Atlas were considered. A total of 9,947 participants across 40 cohorts, followed-up for about 5 years on average, were analyzed comparing patients showing SALL4 presence (SALL4+, n = 1,811) or absence (SALL4-, n = 8,136). All data were summarised using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) for the time-dependent risk related to SALL4+, adjusted for potential confounders. SALL4+ significantly increased overall mortality (RR = 1.34, 95% confidence intervals (CI)=1.21-1.48, p<0.0001, I2=66%; HR=1.4; 95%CI: 1.19-1.65; p<0.0001; I2=63%) and recurrence of disease (RR = 1.25, 95% CI = 1.1-1.42, p=0.0006, I2=62%); HR=1.52; 95% CI: 1.22-1.89, p=0.0002; I2=69%) compared to SALL4-. Moreover, SALL4 remained significantly associated with poor prognosis even using HRs adjusted for potential confounders (overall mortality: HR=1.4; 95%CI: 1.19-1.65; p<0.0001; I2=63%; recurrence of disease: HR=1.52; 95% CI: 1.22-1.89, p=0.0002; I2=69%). These results suggest that SALL4 expression increases both mortality and recurrence of cancer, confirming this gene as an important prognostic marker and a potential target for personalized medicine.

The diagnostic performances of miR-130a expression analysis and IHC appear to be similar. miR-130a quantification could be used reliably as second-level diagnostic tool to differentiate MM from lung AdC in pleural effusion cytology, mainly in those cases with ambiguous or negative IHC. Further validation is needed. Cancer Cytopathol 2017;125:635-43. © 2017 American Cancer Society.

An increased risk of venous thromboembolism (VTE) is present during pregnancy and the main reason is the shift of the hemostatic system toward hypercoagulability. 1 An increase in plasma concentration of some coagulation factors (ie, factors V, VII, VIII, IX, X, XII, fibrinogen, and von Willebrand factor) on one hand and a decrease in free protein S as well as acquired activated protein C resistance on the other was reported. Moreover, microparticles derived from endothelial cells, platelets, and trophoblast can represent additional procoagulant stimuli.2-5 Hypercoagulability during pregnancy is reflected by an increase in coagulation activation markers (ie, prothrombin fragment 1 þ 2, thrombin-antithrombin complexes, soluble fibrin polymer, and D-dimer).6 More recently, thrombin generation (TG) in plasma has been used to assess the endogenous thrombin potential (ETP) in platelet-poor and/or platelet-rich plasma. 7Only few data are available on TG during pregnancy and the results from different observations are conflicting. 8,9 Low-molecular-weight heparin (LMWH) is the anticoagulant treatment of choice for VTE prophylaxis and treatment during pregnancy. Despite the increased risk of VTE during pregnancy and the postpartum period, only women at very high risk like those with previous thrombotic events, particularly if occurred during hormonal treatments, or those with inherited deficiency of natural anticoagulants need anticoagulant prophylaxis during pregnancy and postpartum. 10 However, the optimal dose of LMWH thromboprophylaxis in pregnancy at risk is still unknown. We performed a preliminary study investigating the in vitro effect of low-dose LMWH (Nadroparin; Italfarmaco, Milan, Italy) on TG after the ''in vitro'' addition to plasma from healthy pregnant women during the first trimester. The data obtained were compared with those of a control group of healthy women.Of the 19 women in the first trimester of pregnancy, consecutively referred to the University Hospital of Padua, 3 were excluded because of a history of VTE and/or obstetric complications, 2 because of younger than or equal to 18 years, and 2 because of the intake of any antithrombotic therapy. No women enrolled had a previous diagnosis of hypertension and none had preexisting or gestational diabetes. Thus, 12 healthy pregnant women and 12 healthy nonpregnant women of comparable age were included in the study.After informed consent, 9 mL of blood were drawn through a butterfly needle, from an antecubital vein, into a syringe prefilled with 1 mL of sodium citrate 109 mmol/L. Blood was centrifuged at 3000 rpm for 10 minutes to separate cells from platelet-poor plasma (PPP); PPP was dispensed as 500 mL aliquots and was stored at À80 C. For each participant, prothrombin time ([PT], seconds), activated partial thromboplastin time ([aPTT], seconds), and antithrombin activity (AT, %) were determined. Prothrombin time, aPTT, and AT were performed on a BCT-Analyser (Dade Behring, Marburg, Germany), according to standard procedures.Thrombin generation was...