Politics and Salus Populi: Hobbes and the Sovereign as Physician of the State

In his masterpiece Leviathan (1651), Thomas Hobbes used a series of rhetorical devices in order to persuade the English reader of the truth of his political theories and of his civil science. The first rhetorical device is the engraved frontispiece of the book, where the sword of justice held by the sovereign is also a powerful sword of rhetoric (as shown by the table depicting Rhetoric in a Martianus Capella’s manuscript owned by the Duke of Urbino). Moreover, Hobbes employs directly the metaphor of the state as a body politic and the analogy of the sovereign as the soul of the state and he also refers—though indirectly—to the Platonic analogy of the sovereign as physician of the state, evoking political thinkers, such as King James VI & I and Edward Forset

METUS REVEALED. HOBBES ON FEAR

Fear is a universal emotion, experienced by everybody. When it becomes collective and social, it can enter into the processes of political imagination, being used for political purposes. This article is a brief examination of the meanings and functions of fear(s) in Hobbes’s thought. Some of his views may be ‘historically’ related to his own time, the Seventeenth Century, and others may be linked and confined to his own theory. However, his reflections on the importance of the perturbatio animi of fear for human psychology, and its impact on human interactions and collective behaviour, are still interesting for us today. The various meanings of fear highlighted by Hobbes (especially in his political works: Elements of Law, De cive, and Leviathan) are here synthetically reconstructed, with particular emphasis on fear as passion, expectation and will, and on fear in his various social aspects: mutual fear and fear of death, which give rise to the political community; fear of punishment and fear for the laws, which help to maintain the State and finally, fear of invisible power and timor Dei, from which religion originates, and the religious power that Hobbes wanted to be held by the State

The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines

Mammary serine protease inhibitor or Maspin has been characterized as a class II tumor suppressor gene in several cancer types, among them prostate cancer (CaP). Androgen ablation is an effective therapy for CaP, but with short-term effectiveness, thus new therapeutic strategies are actively sought. The present study is aimed to explore the effects of a glucosamine derivative, 2-(N-Carbobenzyloxy)L-phenylalanylamido-2-deoxy-β-D-glucose (NCPA), on two CaP cell lines, PC3 and LNCaP. In particular we analyzed the impact of NCPA on Maspin production, cell viability and cell cycle progression and apoptosis/necrosis pathway activation has been determined in PC3 and LNCaP cell lines. NCPA is able to stimulate Maspin production in PC3 and not in LNCaP cell lines. NCPA blocks the PC3 cell cycle in G1 phase, by inhibiting Cyclin D1 production and induces the apoptosis, therefore interfering with aggressiveness of this androgen-insensitive cell line. Moreover, NCPA is able to induce the expression of Maspin in LNCaP cell line treated with androgen receptor inhibitor, Bicalutamide, and in turn to stimulate the apoptosis of these cells. These findings suggest that NCPA, stimulating the endogenous production of a tumor suppressor protein, could be useful in the design of new therapeutic strategies for treatment of CaP

Environment and urinary bladder cancer. A historical perspective

Our understanding of aetiological factors associated with urinary bladder cancer has radically improved over the last decades. Cigarette smoking is considered the most important risk factor, even in the industrialised world, while various occupational and environmental exposures to chemicals are also held responsible. The link between bladder cancer and schistosomiasis, highly prevalent in sub-Saharan Africa, Sudan, Egypt, and Yemen, provides input for investigating and potentially preventing bladder carcinogenesis. Growing concern regarding environmental diseases prompts investigation into the historical milestones that have helped disentangle the relationships between health and environment

Correlation between MYC gene rearrangement and MYC protein expression suggests that MYC regulation is more complex than previously known

Since its discovery in the 1970's, MYC oncoprotein has been continuing to fascinate the scientific world and there is a growing interest in the role of MYC in the genesis and prognosis of cancer. Initially MYC was identified as the cellular homologue of the MC29 transforming avian retrovirus. Shortly hereafter, additional related sequences were identified, suggesting that MYC might be part of a larger family of genes. The constellation of MYC effects on genes involved in proliferation has led to the concept of MYC-driven lymphomas, that include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and lymphomas that share morphologic features of DLBCL and BL, officially termed B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (BCLU). Other lymphomas showing MYC over-expression comprises Plasmablastic lymphoma and Plasmacytoma, Double hit/triple hit lymphomas and Anaplastic lymphomas Kinase-positive Large B-cell Lymphoma. MYC aberrations can be detected by standard cytogenetics, interphase fluorescence in situ hybridization (FISH), comparative genomic hybridization and most recently immunohistochemistry. By comparing expression profiles of MYC gene rearrangement and MYC protein expression has came up that MYC gene rearrangements do not necessarily correlate with MYC protein expression. In fact, by applying immunoistochemistry, the frequency of MYC protein expression appears much higher than what is detected by FISH standard method. Therefore, nowadays the key problem in the hematopathology field is to define the clinical impact of the double-expressor lymphoma status. The updated World Health Organization (WHO) of tumours of hematopoietic and lymphoid tissues asses that the status of double or triple lymphoma should rely only on molecular biology findings and not on immunohistochemistry results

Loss of heterozygosis on chromosome 18q21-23 and muscle-invasive bladder cancer natural history

Loss of heterozygosis (LOH) on chromosome (Chr) 18q21-23 was reported to be one of the most common genetic alterations identified in bladder cancer. The current study aimed to determine the prognostic role of LOH on Chr 18q21-23 in patients diagnosed with muscle-invasive urothelial bladder carcinoma (MIBC). A total of 34 consecutive patients were enrolled in the present prospective study. LOH on Chr 18 was assessed by performing multiplex polymerase chain reaction on paired blood and tumour tissue samples from each patient. The following primers were used in the present study: D18S51, MBP LW and MBP H. These data were then compared with follow-up information. The main outcome measure was patient status at the end of the follow-up. Cox regression was used to evaluate the impact of each parameter on cancer-specific survival and the Kaplan Meier test for disease-free survival was plotted in order to estimate survival. Out of 34 patients, 18 (52.9%) exhibited ≥1 alteration in one of the loci analysed on chromosome 18, while 16 (47.1%) revealed no alterations. No correlation was identified with stage (P=0.18) or grade (P=0.06); however, LOH on Chr 18q21-23 was significantly associated with a lower recurrence-free probability (P<0.0001). Kaplan-Meier curves demonstrated a significant association between patient status at follow-up and LOH on Chr 18 (P<0.001). In addition, multivariate analysis identified LOH on Chr 18 (P<0.001) and stage (P=0.01) as independent survival predictors. Furthermore, artificial neural network analysis was consistent with the results of the multivariate analysis. In conclusion, the present study highlighted the role of LOH on Chr 18q21-23 in predicting the clinical outcome of patients with MIBC

IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications

The precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma (NMZL) remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning. Here, we studied the B cell Ig heavy-chain repertoires by next-generation sequencing (NGS) in 30 NMZL cases. Most of the cases were mutated (20/28; 71.5%) with homologies to the respective germ line genes ranging from 85 to 97, 83%, whereas 8/28 (28.5%) were unmutated. In addition, our results show that NMZL cases have a biased usage of specific immunoglobulin heavy-chain variable (IGHV) region genes. Moreover, we documented intraclonal diversity in all (100%) of the mutated cases and ongoing somatic hypermutations (SHM) have been confirmed by hundreds of reads. We analyzed the mutational pattern to detect and quantify antigen selection pressure and we found a positive selection in 4 cases, whereas in the remaining cases there was an unspecific stimulation. Finally, the disease-specific survival and the progression-free survival were significantly different between cases with mutated and unmutated IGHV genes, pointing out mutational status as a possible new biomarker in NMZL