Istituzioni, società , economia in una comunità valdorciana: Montalcino (1361-1462)

The research has as object the analysis of social, political and economic dynamics of Montalcino between 1361 and 1462. The survey takes as its base a large part documentary of the rich documentation (now entirely novel) kept at the Archivio Comunale of Montalcino and at the Archivio di Stato of Siena. In the first part it explains the documentary material. It follows a description of geographical, orografic and hydrografic features. The second part has dedicated to the reconstruction of political events, which is completed by a careful examination of administrative orders. The third part is dedicated to the study of economic and social life of the community. First, attention is directed to the finances of the community. Other topics covered are those with regard to land ownership, agricultural production and livestock. There are specific references to issues relating to the use of common goods and the difficult relationship between agriculture and pastoral practice. The last part of the work is devoted to milling facilities. Given the nature of the sources available, attention was mainly the reconstruction of the events capital of molendina. It was possible, however, get news on the operation of the plant, as well as their structure. The essay is enriched by an documentary: the transcript of the "Statuto dei Danni Dati" (1452); the inventories of the "Spedale di San Cristoforo" (1430) and of the "Società dei Disciplinati di San Pietro" (1418, 1427)

Long-term follow-up of Zoon balanitis: a retrospective cohort study

Dear Editor, Zoon balanitis (ZB) is an infammatory disease afecting genital mucosa, particularly the glans and the inside of the foreski

The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination

Aberrant cholesterol homeostasis and biosynthesis has been observed in different tumour types. This paper investigates the role of the post-squalenic enzyme of cholesterol biosynthesis, oxidosqualene cyclase (OSC), in regulating tumour angiogenesis and metastasis dissemination in mouse models of cancer. We showed that Ro 48-8071, a selective inhibitor of OSC, reduced vascular density and increased pericyte coverage, with a consequent inhibition of tumour growth in a spontaneous mouse model of pancreatic tumour (RIP-Tag2) and two metastatic mouse models of human colon carcinoma (HCT116) and pancreatic adenocarcinoma (HPAF-II). Remarkably, the inhibition of OSC hampered metastasis formation in HCT116 and HPAF-II models. Ro 48-8071 induced tumour vessel normalization and enhanced the anti-tumoral and anti-metastatic effects of 5-fluorouracil (5-FU) in HCT116 mice. Ro 48-8071 exerted a strong anti-angiogenic activity by impairing endothelial cell adhesion and migration, and by blocking vessel formation in angiogenesis assays. OSC inhibition specifically interfered with the PI3K pathway. According to in vitro results, Ro 48-8071 specifically inhibited Akt phosphorylation in both cancer cells and tumour vasculature in all treated models. Thus, our results unveil a crucial role of OSC in the regulation of cancer progression and tumour angiogenesis, and indicate Ro 48-8071 as a potential novel anti-angiogenic and anti-metastatic drug

Black hole scaling relations of active and quiescent galaxies: Addressing selection effects and constraining virial factors

Local samples of quiescent galaxies with dynamically measured black hole masses (Mbh) may suffer from an angular resolution-related selection effect, which could bias the observed scaling relations between Mbh and host galaxy properties away from the intrinsic relations. In particular, previous work has shown that the observed Mbh-Mstar (stellar mass) relation is more strongly biased than the Mbh-sigma (velocity dispersion) relation. Local samples of active galactic nuclei (AGN) do not suffer from this selection effect, as in these samples Mbh is estimated from megamasers and/or reverberation mapping-based techniques. With the exception of megamasers, Mbh-estimates in these AGN samples are proportional to a virial coefficient fvir. Direct modelling of the broad line region suggests that fvir~3.5. However, this results in a Mbh-Mstar relation for AGN which lies below and is steeper than the one observed for quiescent black hole samples. A similar though milder trend is seen for the Mbh-sigma relation. Matching the high-mass end of the Mbh-Mstar and Mbh-sigma relations observed in quiescent samples requires fvir~15 and fvir~7, respectively. On the other hand, fvir~3.5 yields Mbh-sigma and Mbh-Mstar relations for AGN which are remarkably consistent with the expected `intrinsic' correlations for quiescent samples (i.e., once account has been made of the angular resolution-related selection effect), providing additional evidence that the sample of local quiescent black holes is biased. We also show that, as is the case for quiescent black holes, the Mbh-Mstar scaling relation of AGN is driven by velocity dispersion, thus providing additional key constraints to black hole-galaxy co-evolution models.Comment: 15 pages, 5 Figures. MNRAS, accepte

Mechanical ventilation and volutrauma: study in vivo of a healthy pig model

Mechanical ventilation is essential in intensive care units. However, it may itself induce lung injury. Current studies are based on rodents, using exceptionally large tidal volumes for very short periods, often after a "priming" pulmonary insult. Our study deepens a clinically relevant large animal model, closely resembling human physiology and the ventilator setting used in clinic settings. Our aim was to evaluate the pathophysiological mechanisms involved in alveolo/capillary barrier damage due to mechanical stress in healthy subjects. We randomly divided 18 pigs (sedated with medetomidine/tiletamine-zolazepam and anesthetised with thiopental sodium) into three groups (n=6): two were mechanically ventilated (tidal volume of 8 or 20 ml/kg), the third breathed spontaneously for 4 hours, then animals were sacrifi ced (thiopental overdose). We analyzed every 30' hemogasanalysis and the main circulatory and respiratory parameters. Matrix gelatinase expression was evaluated on bronchoalveolar lavage fl uid after surgery and before euthanasia. On autoptic samples we performed zymographic analysis of lung, kidney and liver tissues and histological examination of lung. Results evidenced that high V T evoked profound alterations of lung mechanics and structure, although low V T strategy was not devoid of side effects, too. Unexpectedly, also animals that were spontaneously breathing showed a worsening of the respiratory functions

Publisher Correction: Bridging the gap between measurements and modelling: a cardiovascular functional avatar.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Impact of dobutamine stress on diastolic energetic efficiency of healthy left ventricle: an in vivo kinetic energy analysis

The total kinetic energy (KE) of blood can be decomposed into mean KE (MKE) and turbulent KE (TKE), which are associated with the phase-averaged fluid velocity field and the instantaneous velocity fluctuations, respectively. The aim of this study was to explore the effects of pharmacologically induced stress on MKE and TKE in the left ventricle (LV) in a cohort of healthy volunteers. 4D Flow MRI data were acquired in eleven subjects at rest and after dobutamine infusion, at a heart rate that was ∼60% higher than the one in rest conditions. MKE and TKE were computed as volume integrals over the whole LV and as data mapped to functional LV flow components, i.e., direct flow, retained inflow, delayed ejection flow and residual volume. Diastolic MKE and TKE increased under stress, in particular at peak early filling and peak atrial contraction. Augmented LV inotropy and cardiac frequency also caused an increase in direct flow and retained inflow MKE and TKE. However, the TKE/KE ratio remained comparable between rest and stress conditions, suggesting that LV intracavitary fluid dynamics can adapt to stress conditions without altering the TKE to KE balance of the normal left ventricle at rest

First evidence of heteroplasmy in Grey Partridge (Perdix perdix)

Abstract We report for the first time the occurrence of heteroplasmy in Grey Partridge (Perdix perdix) revealed by means of two mitochondrial fragments. The possible serious biological and management implications of this exception to unilateral inheritance of mtDNA were underlined

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

The mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination

Synthesis, in vitro and in vivo biological evaluation of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones as new potent anticancer agents

A small library of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones has been synthesized and screened according to protocols available at the National Cancer Institute (NCI). Some derivatives were potent antiproliferative agents, showing GI50 values in the nanomolar range. Remarkably, when most active compounds against leukemia cells were tested in human peripheral blood lymphocytes from healthy donors, were 100–200 times less cytotoxic. Some compounds, selected by the Biological Evaluation Committee of NCI, were examined to determine tubulin assembly inhibition. Furthermore, flow cytometric studies performed on HeLa, HT-29, and A549 cells, showed that compounds 14 and 25 caused a block in the G2/M phase. Interestingly, these derivatives induced apoptosis through the mitochondrial death pathway, causing in parallel significant activation of both caspase-3 and -9, PARP cleavage and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1. Finally, compound 25 was also tested in vivo in the murine BL6-B16 melanoma and E0771 breast cancer cells, causing in both cases a significant reduction in tumor volume