Hyperhomocysteinemia as an Early Predictor of Erectile Dysfunction: International Index of Erectile Function (IIEF) and Penile Doppler Ultrasound Correlation With Plasma Levels of Homocysteine

Erectile dysfunction (ED) is inability to achieve and maintain an erection to permit satisfactory sexual activity. Homocysteine (Hcys) is a sulfur-containing amino acid synthesized from the essential amino acid methionine. Experimental models have elucidated the role of hyperhomocysteinemia (HHcys) as a strong and independent predictor for atherosclerosis progression and impaired cavernosal perfusion.The aim of this study is to investigate the serum levels of Hcys in our cohort of patients with ED, to compare these values with these of control population and to examine Hcys as a predictive marker for those patients who are beginning to complain mild–moderate ED.A total of 431 patients were enrolled in the study. The whole cohort was asked to complete the International Index of Erectile Function (IIEF) questionnaire. The study population was divided in 3 main groups: Group A: 145 patients with no ED serving as a control group; Group B: 145 patients with mild or mild–moderate ED; Group C: 141 patients with moderate or severe ED. Each participant underwent blood analysis. All patients underwent baseline and dynamic penile Doppler ultrasonography.We found in our cohort mean Hcys plasma concentrations significantly higher than the cut-off point in both groups B and C (18.6 ± 4.7 and 28.38 ± 7.8, respectively). Mean IIEF score was 27.9 ± 1.39, 19.5 ± 2.6, and 11.1 ± 2.5 for groups A, B, and C, respectively (P < 0.0001). In the penile Doppler ultrasonography studies, a high significant inverse correlation was detected between the mean values of the 10th minute''s peak-systolic velocity (PSV) and Hcys levels for the groups B and C.This establishes a dose-dependent association between Hcys and ED. Furthermore, we showed that Hcys was an earlier predictor of ED than Doppler studies, as the Hcys increase was present in patients with mild ED even before abnormal Doppler values.     

Novel Axl-driven signaling pathway and molecular signature characterize high-grade ovarian cancer patients with poor clinical outcome

High-grade epithelial ovarian cancer (HGEOC) is a clinically diverse and molecularly heterogeneous disease comprising subtypes with distinct biological features and outcomes. The receptor tyrosine kinases, expressed by EOC cells, and their ligands, present in the microenvironment, activate signaling pathways, which promote EOC cells dissemination. Herein, we established a molecular link between the presence of Gas6 ligand in the ascites of HGEOCs, the expression and activation of its receptor Axl in ovarian cancer cell lines and biopsies, and the progression of these tumors. We demonstrated that Gas6/Axl signalling converges on the integrin β3 pathway in the presence of the adaptor protein p130Cas, thus inducing tumor cell adhesion to the extracellular matrix and invasion. Accordingly, Axl and p130Cas were significantly co-expressed in HGEOC samples. Clinically, we identified an Axl-associated signature of 62 genes able to portray the HGEOCs with the shortest overall survival. These data biologically characterize a group of HGEOCs and could help guide a more effective therapeutic approach to be taken for these patients.     

Spatial and temporal bias in the mitotic origins of somatostatin- and parvalbumin-expressing interneuron subgroups and the chandelier subtype in the medial ganglionic eminence

GABAergic interneurons modulate cortical activity through the actions of distinct subgroups. Recent studies using interneuron transplants have shown tremendous promise as cell-based therapies for seizure disorders, Parkinson's disease, and in the study of neocortical plasticity. Previous reports identified a spatial bias for the origins of parvalbumin (PV)- and somatostatin (SST)-expressing interneuron subgroups within the medial ganglionic eminence (MGE). In the current study, the mitotic origins of these interneurons are examined by harvesting MGE cells at 2 time points and evaluating their neurochemical profiles after transplantation into neonatal mouse cortex. Although the dorsal MGE (dMGE)-SST and ventral MGE (vMGE)-PV bias were confirmed, both subgroups originate from progenitors located throughout the MGE. The dMGE bias was also found for SST subgroups that coexpress calretinin or reelin. In contrast, another major subgroup of SST interneuron, neuropeptide Y-expressing, does not appear to originate within the MGE. Finally, novel evidence is provided that a clinically important subtype of PV-expressing interneuron, the chandelier (axo-axonic) cell, is greatly enriched in transplants from the vMGE at embryonic day 15. These findings have important implications both for the study of interneuron fate determination and for studies that use interneuron precursor transplantation to alter cortical activity.     

Searching for Indicators of Malignancy in Pancreatic Intraductal Papillary Mucinous Neoplasms: The Value of 18FDG–PET Confirmed

Background

Malignancy in intraductal papillary mucinous neoplasms (IPMN) of the pancreas may be predicted on the basis of a number of clinical and radiologic features, which have raised sensitivity but result in a specificity as low as 20?C50%. We sought to confirm the additional value of ¹⁸F-18-fluorodeoxyglucose?Cpositron emission tomography (¹⁸FDG?CPET) in diagnostic accuracy of imaging-based IPMN malignancy assessment.

Methods

This prospective uncontrolled case series contained 44 patients with IPMN undergoing comprehensive diagnostic evaluation, including magnetic resonance cholangiopancreatography and ¹⁸FDG?CPET. Average follow-up time was 39.3?months (range 3?C97?months). Diagnostic performance regarding the diagnosis of malignancy was evaluated for the classic preoperative assessment, including clinical signs, CA 19-9, imaging (computed tomography and magnetic resonance cholangiopancreatography), and International Consensus Guidelines criteria, as well as ¹⁸FDG?CPET scan.

Results

Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100, 22, 32, 100, and 43%, and 83, 100, 100, 94, and 96%, respectively, for comprehensive assessment without and with ¹⁸FDG?CPET [maximum standardized uptake value (SUV_max) cutoff of 2.5?MBq]. Elevated CA 19-9 values and positive PET scan were the only independent prognostic factors for malignancy (odds ratio 2.11, 95% confidence interval 1.15?C2.74 and 5.49, 95% confidence interval 3.98?C21.44, respectively).

Conclusions

¹⁸FDG?CPET is useful for detection of malignancy in IPMN, improving the differential diagnosis with benign cases by functional data. The choice of SUV_max cutoff should maximize specificity.     

Non invasive continuous hemodynamic evaluation of cirrhotic patients after postural challenge

AIM: To assess whether Most Care is able to detect the cardiovascular alterations in response to physiological stress (posture). METHODS: Non invasive hemodynamic was assessed in 26 cirrhotic patients compared to healthy subjects, both in the supine and standing positions. RESULTS: In baseline conditions, when compared to healthy subjects, cirrhotic patients showed significantly lower values of dicrotic and diastolic pressures and systemic vascular resistance. While in the standing position, cirrhotic patients showed higher values of cardiac index, stroke volume index and cardiac cycle efficiency. When returning to the supine position, cirrhotic patients exhibited lower values of dicrotic and diastolic pressures and systemic vascular resistance in the presence of higher values of cardiac index, stroke volume index and cardiac cycle efficiency.