Sante De Sanctis (1862-1935), a forerunner of the 20th century research on sleep and dreaming

This article aims to reconstruct the elements of continuity and/or discontinuity in Sante De Sanctis' (1862–1935) contributions in the scientific understanding of sleep and dreaming as compared to the scientific research of his time. An Italian psychologist and psychiatrist, De Sanctis, in his work conducted between the 19th and 20th centuries, has framed the study of dreams using multi-methodology. In addition, De Sanctis experimentally established the correspondence between the deep and desynchronization phases of sleep with respect to dreaming. In this context, De Sanctis' subjects described the periodicity of sleep and consciousness, influencing the explanations of the themes that modern sleep research has, after decades, systematically studied. We demonstrate that De Sanctis' work has been underestimated, and in our opinion, deserves to be reconsidered as a source of the psychophysiological explanation of dreams and sleep. Finally, we present a graphical representation of De Sanctis' psycho- and neurophysiological model of dreamin

Higher order approximation of the period-energy function for single degree of freedom Hamiltonian Systems

In 1985 Franz Rothe [16] found, by means of the thermodynamical equilibrium theory, an asymptotic estimate of period of solutions of Ordinary Differential Equations originated by predator - prey Volterra – Lotka model. We extend some of Rothe’s ideas to more general systems and succeed in calculating the period’s asymptotic analytic expression as a function of the energy level. We finally check our result reobtaining classical period’s estimation of some popular Hamiltonian systems. We apply our technique also to a nonlinear Hamiltonian system whose period is not available in the literature

Sorafenib and Regorafenib in HBV- or HCV-positive hepatocellular carcinoma patients: Analysis of RESORCE and SHARP trials

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Radiofrequency Ablation of hepatocellular carcinoma: a meta-analysis of overall survival and recurrence-free survival

Background and aims So far, no randomized trial or meta-analysis has been conducted on overall survival (OS) and recurrence-free survival (RFS) factors in patients treated with radiofrequency ablation (RFA) alone. The purpose of this meta-analysis was to evaluate prognostic factors of OS and RFS in patients treated with RFA. Methods A primary analysis was planned to evaluate the clinical prognostic factor of OS. RFS was the secondary aim. Thirty-four studies published from 2003 to 2017 were analyzed. They included 11,216 hepatocellular carcinoma patients. Results The results showed that Child\u2013Pugh B vs Child\u2013Pugh A (HR =2.32; 95% CI: 2.201\u20132.69; P<0.0001) and albumin\u2013bilirubin score 1 vs 0 (HR =2.69; 95% CI: 2.10\u20133.44; P<0.0001) were predictive of poor OS. Tumor size as a continuous variable was not predictive of OS, although it was predictive of OS when we considered the size as a cutoff value (.2 cm vs <2 cm: HR =1.41; 95% CI: 1.23\u20131.61; P<0.0001; >3 cm vs <3 cm: HR =1.43; 95% CI: 1.17\u20131.74; P<0.0001) and in presence of >1 nodule (HR =1.59; 95% CI: 1.46\u20131.74; P<0.0001). Alpha-fetoprotein >20 ng/mL (HR =1.46; 95% CI: 1.25\u20131.70; P<0.0001) was the only predictive factor of poor prognosis. Conclusion Our meta-analysis highlighted that the maximum benefit of RFA in terms of OS and RFS is reached in the presence of Child\u2013Pugh A, albumin\u2013bilirubin score 1, single-nodule tumor sized <2 cm, and alpha-fetoprotein <20 ng/mL

Antiangiogenic agents after first line and sorafenib plus chemoembolization: A systematic review

Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage, although the combination of TACE with sorafenib may theoretically benefit HCC patients in intermediate stage. Owing to the significant antiangiogenic effect of sorafenib and the limitation of TACE, it is rational to combine them. Though the strategy of combining TACE and sorafenib has been increasingly used in patients with unresectable HCC but the current evidence is controversial and its clinical role has not been determined yet. In first-line therapy, patients receiving sorafenib had increased overall survival and progression free survival. Therefore several antiangiogenic agents have entered clinical studies on HCC, many with negative results. This review discusses the current drug development for patients with HCC and role of TACE plus sorafenib

Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells\u2019 extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet\u2013tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Interplay Between SIRT-3, Metabolism and Its Tumor Suppressor Role in Hepatocellular Carcinoma

Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD + )-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC). SIRT-3 regulatory effect and involvement in metabolism dysfunctions may have strong implications in HCC development and treatment. Research literature widely reports the relationship between metabolic disorders and HCC development. This evidence suggests a putative bridge role of SIRT-3 between metabolic diseases and HCC. However, further studies are necessary to demonstrate such interconnection

Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; Potential marker of disease recurrence

Background: Epigenetic alterations of specific genes have been reported to be related to colorectal cancer (CRC) transformation and would also appear to be involved in the early stages of colorectal carcinogenesis. Little data are available on the role of these alterations in determining a different risk of colorectal lesion recurrence. The aim of the present study was to verify whether epigenetic alterations present in pre-neoplastic colorectal lesions detected by colonoscopy can predict disease recurrence. Methods. A retrospective series of 78 adenomas were collected and classified as low (35) or high-risk (43) for recurrence according to National Comprehensive Cancer Network guidelines. Methylation alterations were analyzed by the methylation-specific multiplex ligation probe assay (MS-MLPA) which is capable of quantifying methylation levels simultaneously in 24 different gene promoters. MS-MLPA results were confirmed by pyrosequencing and immunohistochemistry. Results: Higher levels of methylation were associated with disease recurrence. In particular, MLH1, ATM and FHIT gene promoters were found to be significantly hypermethylated in recurring adenomas. Unconditional logistic regression analysis used to evaluate the relative risk (RR) of recurrence showed that FHIT and MLH1 were independent variables with an RR of 35.30 (95% CI 4.15-300.06, P = 0.001) and 17.68 (95% CI 1.91-163.54, P = 0.011), respectively. Conclusions: Histopathological classification does not permit an accurate evaluation of the risk of recurrence of colorectal lesions. Conversely, results from our methylation analysis suggest that a classification based on molecular parameters could help to define the mechanisms involved in carcinogenesis and prove an effective method for identifying patients at high risk of recurrence