Cryotop vitrification of human oocytes results in high survival rate and healthy deliveries

Vitrification, an ultra-rapid cooling technique, offers a new perspective in attempts to develop an optimal cryopreservation procedure for human oocytes and embryos. To further evaluate this method for human oocytes, 796 mature oocytes (metaphase II) were collected from 120 volunteers. Since Italian legislation allows the fertilization of a maximum of only three oocytes per woman, there were 463 supernumerary oocytes; instead of being discarded, they were vitrified. When, in subsequent cycles, these oocytes were utilized, 328 out of 330 (99.4%) oocytes survived the warming procedure. The fertilization rate, pregnancy rate and implantation rate per embryo were 92.9, 32.5 and 13.2% respectively. Thus, as already reported in the literature, the vitrification procedure seems to be highly effective, safe (since healthy babies have been born) and easy to apply. In situations where embryo cryopreservation is not permitted (as in Italy), there is now good indication for routine application of the method, once further standardization is achieved.     

Scouting new molecular targets for CFTR therapy: the HSC70/BAG-1 complex. A computational study

HSC70 has been identified as an important molecular target involved in the ΔF508-CFTR cystic fibrosis. HSC70 associates ΔF508-CFTR to a much greater extent than WT-CFTR and after this step, it recruits other co-chaperones (BAG1, CHIP) and performs the ubiquitination and proteosomal degradation of the protein. Up to now, several X-ray data concerning the HSC70:BAG1 complexes are available. Thus, we performed an “in silico” investigation focused to explore which different amino acid residues are involved in the binding of ATP, the natural substrate, and the co-crystallized ligands at the HSC70/BAG-1 interface. The study allowed us to evaluate sildenafil and KM11060, which proved to be also CFTR correctors, as potential HSC70:BAG1 inhibitors, and also let us derive interesting perspectives for the development of new CFTR correctors.     

The M1/M4 preferring muscarinic agonist xanomeline modulates functional connectivity and NMDAR antagonist-induced changes in the mouse brain

Cholinergic drugs acting at M1/M4 muscarinic receptors hold promise for the treatment of symptoms associated with brain disorders characterized by cognitive impairment, mood disturbances, or psychosis, such as Alzheimer’s disease or schizophrenia. However, the brain-wide functional substrates engaged by muscarinic agonists remain poorly understood. Here we used a combination of pharmacological fMRI (phMRI), resting-state fMRI (rsfMRI), and resting-state quantitative EEG (qEEG) to investigate the effects of a behaviorally active dose of the M1/M4-preferring muscarinic agonist xanomeline on brain functional activity in the rodent brain. We investigated both the effects of xanomeline per se and its modulatory effects on signals elicited by the NMDA-receptor antagonists phencyclidine (PCP) and ketamine. We found that xanomeline induces robust and widespread BOLD signal phMRI amplitude increases and decreased high-frequency qEEG spectral activity. rsfMRI mapping in the mouse revealed that xanomeline robustly decreased neocortical and striatal connectivity but induces focal increases in functional connectivity within the nucleus accumbens and basal forebrain. Notably, xanomeline pre-administration robustly attenuated both the cortico-limbic phMRI response and the fronto-hippocampal hyper-connectivity induced by PCP, enhanced PCP-modulated functional connectivity locally within the nucleus accumbens and basal forebrain, and reversed the gamma and high-frequency qEEG power increases induced by ketamine. Collectively, these results show that xanomeline robustly induces both cholinergic-like neocortical activation and desynchronization of functional networks in the mammalian brain. These effects could serve as a translatable biomarker for future clinical investigations of muscarinic agents, and bear mechanistic relevance for the putative therapeutic effect of these class of compounds in brain disorders.Subject terms: Schizophrenia, Translational research, Preclinical research     

Instrumental,clinical and subjective evaluation of the efficacy of a cosmetic treatment for home use

Background: In the last few years, there has been increasing demand for aesthetic procedures to improve the effects of skin aging.

Aim: To evaluate the anti-aging efficacy, tolerability and skin changes induced by the topical products containing hyaluronic acid, N-acetyl glucosamine and gamma-amino butyric acid through instrumental techniques, clinical and subjective evaluation.

Patients/Method: Twenty female enrolled applied a day and night cream after applying a serum, once week applied a mask, for 2 months. A clinical assessment of smoothness, expression wrinkles, fine wrinkles and measurements of the parameters using Reveal Imager, X-Rite, Corneometer, Dermalab, Moisture Meter EpiD were taken at day 0, 15, 30 and 60 of study period. A final assessment questionnaire was submitted.

Results: The products were accepted by all the volunteers. The hydration (Corneometer: T0 49.17 vs T60 61.11, average variation 24.28%) (Moisture Meter EpiD: T0 45.73 vs T60 61.10, average variation 33.60%), elasticity (Dermalab: T0 56.06 vs T60 62.78, average variation 11.98%) and lightening of the skin (X-Rite: T0 60.23 vs T60 63.36, average variation 5.26%) improved. All changes were statistically significant (p < 0.05).

Conclusion: The efficacy of the topical products is confirmed by subjective, clinical and instrumental assessment. This should be a routine approach in dermatologic practice.     

Epidemiological,demographic and clinical data on chronic viral hepatitis C in Tuscany

Background: Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries’ economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy.

Methods: We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress.

Results: Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44?±?15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin’s lymphoma in 10.5%).

Conclusions: Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.