Near-infrared spectroscopy study of tourniquet-induced forearm ischaemia in patients with coronary artery disease

Near-Infrared Spectroscopy (NIRS) can be employed to monitor local changes in haemodynamics and oxygenation of human tissues. A preliminary study has been performed in order to evaluate the NIRS transmittance response to induced forearm ischaemia in patients with coronary artery disease (CAD). The population consists in 40 patients with cardiovascular risk factors and angiographically documented CAD, compared to a group of 13 normal subjects. By inflating and subsequently deflating a cuff placed around the patient arm, an ischaemia has been induced and released, and the patients have been observed until recovery of the basal conditions. A custom NIRS spectrometer (IRIS) has been used to collect the backscattered light intensities from the patient forearm throughout the ischaemic and the recovery phase. The time dependence of the near-infrared transmittance on the control group is consistent with the available literature. On the contrary, the magnitude and dynamics of the NIRS signal on the CAD patients show deviations from the documented normal behavior, which can be tentatively attributed to abnormal vessel stiffness. These preliminary results, while validating the performance of the IRIS spectrometer, are strongly conducive towards the applicability of the NIRS technique to ischaemia analysis and to endothelial dysfunction characterization in CAD patients with cardiovascular risk factors

Delay of morphine tolerance by palmitoylethanolamide

In spite of the potency and efficacy of morphine, its clinical application for chronic persistent pain is limited by the development of tolerance to the antinociceptive effect. The cellular and molecular mechanisms underlying morphine tolerance are complex and still unclear. Recently, the activation of glial cells and the release of glia-derived proinflammatory mediators have been suggested to play a role in the phenomenon. N-Palmitoylethanolamine (PEA) is an endogenous compound with antinociceptive effects able to reduce the glial activation. On this basis, 30 mg kg−1 PEA was subcutaneously daily administered in morphine treated rats (10 mg kg−1 intraperitoneally, daily). PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy in comparison to the vehicle + morphine group. PEA prevented both microglia and astrocyte cell number increase induced by morphine in the dorsal horn; on the contrary, the morphine-dependent increase of spinal TNF-α levels was not modified by PEA. Nevertheless, the immunohistochemical analysis revealed significantly higher TNF-α immunoreactivity in astrocytes of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from astrocyte. PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid-based therapies is suggested

INTERCOMPARISON, SENSITIVITY AND UNCERTAINTY ANALYSIS BETWEEN DIFFERENT URBAN DISPERSION MODELS APPLIED TO AN AIR QUALITY ACTION PLAN IN TUSCANY, ITALY

The Tuscan Regional Administration funded project MoDiVaSET-2 (MOdellistica DIffusionale per la VAlutazione di Scenari Emissivi in Toscana 2) was established in order to develop a decision support modelling system for implementing the Air Quality Action Plan for the metropolitan area of Florence, Prato and Pistoia. The objective of the work is to build an integrated meteorological and dispersion models for simulating and evaluating different future emission scenarios of PM10, NOx and NO2 in the study area. With this purpose, the project included several 1-year long dispersion modelling applications and a detailed evaluation study, including sensitivity, validation and uncertainty analysis. Several dispersion models (ADMS-Urban, CALPUFF, CALINE4, SAFE AIR II and CALGRID) were applied and evaluated against monitoring data; the intercomparison between different models is crucial in order to develop reliable modelling techniques. The obtained results point out the importance of including the following critical factors: smaller scale effects (monitoring stations are often located in complex environments; this implies a decrease in the effectiveness of validation studies) and secondary pollution (primary PM10 levels are only a small part of the total PM10 concentrations; much of the urban PM10 is actually produced by chemical transformations and other physical mechanisms, for example, resuspension). In order to understand the weight of these issues, further modelling options (full chemistry and street canyon simulations) were investigated by using CAMx and smaller scale nested models. All the factors listed above affected the evaluation work. However, this does not alter the validity of the scenario analysis, because it is based on the differences between calculated primary pollutants concentrations

Role of Nitric Oxide, Nitric Oxide Synthase, Soluble Guanylyl Cyclase, and cGMP-Dependent Protein Kinase I in Mouse Stem Cell Cardiac Development

Introduction and Aim. Nitric oxide (NO) can trigger cardiac differentiation of embryonic stem cells (ESCs), indicating a cardiogenic function of the NO synthetizing enzyme(s) (NOS). However, the involvement of the NO/NOS downstream effectors soluble guanylyl cyclase (sGC) and cGMP activated protein kinase I (PKG-I) is less defined. Therefore, we assess the involvement of the entire NO/NOS/sGC/PKG-I pathway during cardiac differentiation process. Methods. Mouse ESCs were differentiated toward cardiac lineages by hanging drop methodology for 21 days. NOS/sGC/PKG-I pathway was studied quantifying genes, proteins, enzymatic activities, and effects of inhibition during differentiation. Percentages of beating embryoid bodies (mEBs) were evaluated as an index of cardiogenesis. Results and Discussion. Genes and protein expression of enzymes were increased during differentiation with distinctive kinetics and proteins possessed their enzymatic functions. Exogenous administered NO accelerated whereas the blockade of PKG-I strongly slowed cardiogenesis. sGC inhibition was effective only at early stages and NOS blockade ineffective. Of NOS/sGC/PKG-I pathway, PKG-I seems to play the prominent role in cardiac maturation. Conclusion. We concluded that exogenous administered NO and other pharmacological strategies able to increase the activity of PKG-I provide new tools to investigate and promote differentiation of cardiogenic precursors

Partecipazione dei lavoratori e licenziamenti collettivi

Il saggio, prendendo spunto dal pensiero di Mario Napoli, esamina il ruolo del confronto sindacale nell'ambito dei licenziamenti collettivi. Pur se astrattamente valorizzato, il confronto sindacale \ue8 stato depotenziato dalle recenti riforme e pronunce giurisprudenziali.The essay, taking the cue from Mario Napoli's thought, deals with the role of negotiation between the employer and trade unions in the field of collective dismissals. Although in theory this negotiation is very important, it has been recently weakened not only by the legislator, but also but some judicial decisions

Povertà e lavoro: le nuove sfide per il diritto

Sommario: 1. Il contrasto alla povertà: alle radici del diritto del lavoro. 2. La laboriosità come antidoto alla povertà nel diritto del lavoro repubblicano. 3. I diritti di chi è senza lavoro: ammortizzatori sociali e servizi per l’impiego contro la povertà. 4. Dalla laboriosità alla cittadinanza: la lunga marcia dell’assistenza sociale contro la povertà. 5. Le sfide del nuovo millennio e l’impatto della pandemia: la povertà dentro e fuori il lavoro. 6. La lotta alla povertà oltre la pandemia: la centralità del lavoro.The article, by leveraging the constitutional interpretation, identifies Labour Law, understood in the broad meaning which comprises Social Security Law, as the main tool of the legal order aimed at overcoming poverty and upholding human dignity. After having briefly outlined the historical evolution of the discipline and pointed out the aspects which mainly contribute to fight poverty, in the labour market and in the labour relationship, the author focuses upon the most recent challenges, which bring about new forms of poverty: deregulation, digital transformation of the economy, and now, pandemic. In the last paragraph the author conducts a critical assessment of the legislative initiatives in progress, comprising those laid down in the National Recovery and Resilience Plan, and presents his own suggestions for a revision of Labour Law which is able to strengthen its effectivenes in contrasting old and new forms of poverty, by keeping the centrality of work, understood as a right and a duty of every citizen, placed at the core of the republican pact

Relationship between hospital volume and short-term outcomes: A nationwide population-based study including 75,280 rectal cancer surgical procedures

There is growing interest on the potential relationship between hospital volume (HV) and outcomes as it might justify the centralization of care for rectal cancer surgery. From the National Italian Hospital Discharge Dataset, data on 75,280 rectal cancer patients who underwent elective major surgery between 2002 and 2014 were retrieved and analyzed. HV was grouped into tertiles: low-volume performed 1-12, while high-volume hospitals performed 33+ procedures/year. The impact of HV on in-hospital mortality, abdominoperineal resection (APR), 30-day readmission, and length of stay (LOS) was assessed. Risk factors were calculated using multivariate logistic regression. The proportion of procedures performed in low-volume hospitals decreased by 6.7 percent (p<0.001). The rate of in-hospital mortality, APR and 30-day readmission was 1.3%, 16.3%, and 7.2%, respectively, and the median LOS was 13 days. The adjusted risk of in-hospital mortality (OR = 1.49, 95% CI = 1.25-1.78), APR (OR 1.10, 95%CI 1.02-1.19), 30-day readmission (OR 1.49, 95%CI 1.38-1.61), and prolonged LOS (OR 2.29, 95%CI 2.05-2.55) were greater for low-volume hospitals than for high-volume hospitals. This study shows an independent impact of HV procedures on all short-term outcome measures, justifying a policy of centralization for rectal cancer surgery, a process which is underwa

Boosting Interleukin-12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR-Tagged Nanogold.

AbstractThe clinical use of interleukin‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. The hypothesis is addressed that gold nanoparticles tagged with a tumor‐homing peptide containing isoDGR, an αvβ3‐integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, gold nanospheres are functionalized with the head‐to‐tail cyclized‐peptide CGisoDGRG (Iso1) and murine IL12. The resulting nanodrug (Iso1/Au/IL12) is monodispersed, stable, and bifunctional in terms of αvβ3 and IL12‐receptor recognition. Low‐dose Iso1/Au/IL12, equivalent to 18–75 pg of IL12, induces antitumor effects in murine models of fibrosarcomas and mammary adenocarcinomas, with no evidence of toxicity. Equivalent doses of Au/IL12 (a nanodrug lacking Iso1) fail to delay tumor growth, whereas 15 000 pg of free IL12 is necessary to achieve similar effects. Iso1/Au/IL12 significantly increases tumor infiltration by innate immune cells, such as NK and iNKT cells, monocytes, and neutrophils. NK cell depletion completely inhibits its antitumor effects. Low‐dose Iso1/Au/IL12 can also increase the therapeutic efficacy of adoptive T‐cell therapy in mice with autochthonous prostate cancer. These findings indicate that coupling IL12 to isoDGR‐tagged nanogold is a valid strategy for enhancing its therapeutic index and sustaining adoptive T‐cell therapy