Health conditions of inmates in Italy

Abstract Background Several studies have shown that prison is characterized by a higher prevalence of chronic diseases than unconfined settings. The aim of this study was to describe the characteristics and health of inmates, focusing on internal diseases. Methods We designed a specific clinical record using the Python programming language. We considered all of the diagnoses according to the ICD-9-CM. Results Of a total of 17,086 inmates, 15,751 were enrolled in our study (M = 14,835; F = 869), corresponding to 92.2% of the entire inmate population (mean age of 39.6 years). The project involved a total of 57 detention facilities in six Italian regions (for a total of 28% of all detainees in Italy), as counted in a census taken on February 3, 2014. From the entire study sample, 32.5% of prisoners did not present any disorders, while 67.5% suffered from at least one disease. The most frequent pathologies were psychiatric (41.3%), digestive (14.5%), infectious (11.5%), cardiovascular (11.4%), endocrine, metabolic, and immune (8.6%), and respiratory (5.4%). Conclusion The findings showed that a large number of detainees were affected by several chronic conditions such as hypertension, dyslipidemia and type 2 diabetes mellitus, with an unusually high prevalence for such a young population. Therefore, a series of preventive measures is recommended to strengthen the entire care process and improve the health and living conditions of prisoners

Effetti di tipologie di suolo e colture foraggere sulle perdite per ruscellamento di azoto, fosforo e potassio in differenti areali italiani

Le colture foraggere svolgono un ruolo importante in molti areali italiani. Per una corretta pianificazione del territorio agricolo è necessario approfondire la conoscenza non solo delle caratteristiche produttive di queste colture, ma anche dei loro rapporti con l'ambiente. Questo lavoro prende in considerazione le perdite di azoto, fosforo e potassio dovute al ruscellamento in colture foraggere a diverso livello di intensificazione (dal pascolo alla coltura di erba medica, dal mais al doppio ciclo di mais e loiessa) in tre ambienti italiani: la Pianura Padana nord-occidentale, l'Appennino Toscano e la pianura sarda, con suoli varianti da franco-sabbioso a franco-argilloso. Il monitoraggio quanti-qualitativo del ruscellamento è stato fatto per periodi variabili da due a sei anni. La pendenza era dello 0,5% per gli appezzamenti in Piemonte e Sardegna e del 10% in Toscana. Per quanto riguarda l'azoto i rilasci sono risultati più bassi nei terreni più pianeggianti, anche per i ridotti volumi di ruscellamento registrati, non superando mai 15 kg di N ha -1 anno -1. Nei terreni in pendenza si sono invece registrati valori più elevati, con un massimo annuale di circa 30 kg ha -1 anno -1 di azoto, in relazione anche all'elevato ruscellamento ed erosione di un evento eccezionale. Per il fosforo solo in pochi casi si sono raggiunte perdite di 5 kg ha -1 anno -1, mentre nella maggior parte dei casi non sono stati superati 2 kg ha -1 anno -1. In Sardegna i rilasci di tale elemento sono da considerarsi pressoché trascurabili. Le perdite di potassio sono risultate minime in Sardegna e massime in Piemonte, dove si sono registrati valori dell' ordine di 10 kg ha -1 anno -1. Ove era possibile il confronto, si è verificato che le colture prative riducono il rilascio di elementi nutritivi rispetto alla coltura del mais e che la qualità delle acque di superficie appare legata piuttosto alle tecniche colturali che alla tipologia di suolo. Fodder crops play an important role in many Italian environments. The knowledge of the main productive characteristics of these crops is as important as their relationships with the environment, expecially for a proper territorial management. This paper compares nitrogen, phosphorous and potassium contents in runoff of some forage crops of different intensity (pasture, lucerne, silage maize, Italian ryegrass/maize double cropping) in different ltalian environments (north-western plain of Piemonte, Apennines hills of Tuscany and Mediterranean plain of Sardegna) on different typology of soils. Runoff data have been collected for periods ranging between two and six year, from plots of different extension and slope (0,5% in the plains, 10% in Apennine hills). Nitrogen losses, for the small amount of runoff, have been qui te low from ilat fields, being always less than 15 kg ha -1 year-1. Losses from slope fields have been higher, with a maximum of 30 kg ha -1 year-1, due to very high level of runoff and erosion in a conspicuous episode. Phosphorous losses only in a few cases were higher than 5 kg ha -I year -I, while mostly they have b>!en less than 2 kg ha -1 year-1. In the Mediterranean plain such losses have been quite insignificant. Minimum potassium 10sses were recorded in the Mediterranean plain, while in north-western plain they reached about 10 kg-1 year-1. Maize was, on average, the crop with highest nutrient losses, while quality of the runoff water was more related to agricultural practices than to soil types

Modellizzazione della lisciviazione dei nitrati: calibrazione e validazione del modello LEACHN in diversi suoli e colture foraggere

The LEACHN model calibration and validation was realized in three Italian enviroments (Piedmont, Tuscany and Sardinia), using nitrate losses by drainage from 4 soil types ranging from sandy-loam to day-loam. A set of large drainage lysimeters were used to obtain leaching data. In each location one lysimeter was cultivated with lucerne, while the others were cropped with widespread crops in the area (maize for silage in Piedmont and Sardinia and permanent pasture in Tuscany). Measured leaching losses ranged from l to 68 kg ha-1 year-1. The calibration parameters were humus mineralization rate and nitrification rate. The calibration was realized on a not nitrogen fixing crop, while the validation was executed on lucerne, even if there is not a specific N-fixation subroutine in LEACHN. After calibration, the prediction of nitrate losses cumulated over the whole period (two years) or over each month resulted acceptable for all crops, while the single event prediction was totally inadequate. The LEACHN model seems to be applicable for the nitrate leaching prediction on a territorial scale. In tre areali italiani (pianura piemontese, conca interappenninica toscana, pianura irrigua sarda) e su quattro diversi tipi di terreno si è calibrato e validato il modello LEACHN relativamente alla previsione della lisciviazione dei nitrati. Si è operato con lisimetri a drenaggio di grandi dimensioni. In tutte le situazioni un lisimetro era coltivato a erba medica, mentre altri con colture di ampia diffusione nell'arcale: mais da trinciato integrale in Piemonte, doppio ciclo colturale di loiessa e mais da granella in Sardegna e pascolo in Toscana e Sardegna. Le perdite per lisciviazione misurate sono risultate comprese tra l e 68 kg ha-1 anno-1 di NO-3-N. Come parametri di calibrazione si sono usati il tasso di mineralizzazione dell'humus e il tasso di nitrificazione dello ione ammonio, calibrati sulla coltura non azotofissatrice. Sull'erba medica, per la quale non è prevista alcuna routine per l'azotofissazione, è stata invece condotta la validazione. Dopo la calibrazione, la simulazione della lisciviazione cumulata e dei totali mensili lisciviati è risultata accettatile, anche su erba medica, mentre quella dei singoli eventi è stata del tutto insufficiente. Il modello nel complesso è apparso applicabile per la predizione delle perdite di nitrati anche su scala territoriale

Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory.</p> <p>Results</p> <p>We investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM) as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006) in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice.</p> <p>Conclusion</p> <p>In conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both <it>in vitro </it>and <it>in vivo</it>, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.</p

Cytokine Induced Killer cells are effective against sarcoma cancer stem cells spared by chemotherapy and target therapy

Metastatic bone and soft tissue sarcomas often relapse after chemotherapy (CHT) and molecular targeted therapy (mTT), maintaining a severe prognosis. A subset of sarcoma cancer stem cells (sCSC) is hypothesized to resist conventional drugs and sustain disease relapses. We investigated the immunotherapy activity of cytokine induced killer cells (CIK) against autologous sCSC that survived CHT and mTT. The experimental platform included two aggressive bone and soft tissue sarcoma models: osteosarcoma (OS) and undifferentiated-pleomorphic sarcoma (UPS). To visualize putative sCSC we engineered patient-derived sarcoma cultures (2 OS and 3 UPS) with a lentiviral sCSC-detector wherein the promoter of stem-gene Oct4 controls the expression of eGFP. We visualized a fraction of sCSC (mean 24.2 +/- 5.2%) and confirmed their tumorigenicity in vivo. sCSC resulted relatively resistant to both CHT and mTT in vitro. Therapeutic doses of doxorubicin significantly enriched viable eGFP(+)sCSC in both OS (2.6 fold, n = 16) and UPS (2.3 fold, n = 29) compared to untreated controls. Treatment with sorafenib (for OS) and pazopanib (for UPS) also determined enrichment (1.3 fold) of viable eGFP(+)sCSC, even if less intense than what observed after CHT. Sarcoma cells surviving CHT and mTT were efficiently killed in vitro by autologous CIK even at minimal effector/target ratios (40:1 = 82%, 1:4 = 29%, n = 13). CIK immunotherapy did not spare sCSC that were killed as efficiently as whole sarcoma cell population. The relative chemo-resistance of sCSC and sensitivity to CIK immunotherapy was confirmed in vivo. Our findings support CIK as an innovative, clinically explorable, approach to eradicate chemo-resistant sCSC implicated in tumor relapse

Parp1 inhibitor and trabectedin combination does not increase tumor mutational burden in advanced sarcomas—a preclinical and translational study

SIMPLE SUMMARY: Immunotherapy has revolutionized cancer treatment, but not for all tumor types. Indeed, sarcomas are considered “immune-cold” tumors, which are relatively unresponsive to immunotherapy. One strategy to potentiate immunotherapy efficacy is to increase tumor immunogenicity, for instance by boosting the number of candidate targets (neoantigens) to be recognized by the immune system. Tumor mutational burden indicates the number of somatic mutations identified in the tumor and normalized per megabase. Tumor mutational burden is considered as an acceptable, measurable surrogate of tumor neoantigens. Here, we explored whether the combination of two DNA-damaging agents, trabectedin and olaparib, could increase tumor mutational burden in sarcomas, to prime subsequent immunotherapy. We found no variation in tumor mutational burden after trabectedin + olaparib in preclinical and clinical samples. Therefore, other aspects should be considered to increase sarcoma immunogenicity, by exploiting different pathways such as the potential modulation of the tumor microenvironment induced by trabectedin + olaparib. ABSTRACT: Drug-induced tumor mutational burden (TMB) may contribute to unleashing the immune response in relatively “immune-cold” tumors, such as sarcomas. We previously showed that PARP1 inhibition perpetuates the DNA damage induced by the chemotherapeutic agent trabectedin in both preclinical models and sarcoma patients. In the present work, we explored acquired genetic changes in DNA repair genes, mutational signatures, and TMB in a translational platform composed of cell lines, xenografts, and tumor samples from patients treated with trabectedin and olaparib combination, compared to cells treated with temozolomide, an alkylating agent that induces hypermutation. Whole-exome and targeted panel sequencing data analyses revealed that three cycles of trabectedin and olaparib combination neither affected the mutational profiles, DNA repair gene status, or copy number alterations, nor increased TMB both in homologous recombinant-defective and proficient cells or in xenografts. Moreover, TMB was not increased in tumor specimens derived from trabectedin- and olaparib-treated patients (5–6 cycles) when compared to pre-treatment biopsies. Conversely, repeated treatments with temozolomide induced a massive TMB increase in the SJSA-1 osteosarcoma model. In conclusion, a trabectedin and olaparib combination did not show mutagenic effects and is unlikely to prime subsequent immune-therapeutic interventions based on TMB increase. On the other hand, these findings are reassuring in the increasing warning of treatment-induced hematologic malignancies correlated to PARP1 inhibitor use

The combination of sorafenib and everolimus shows antitumor activity in preclinical models of malignant pleural mesothelioma

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention. This study aimed to identify ‘druggable’ pathways in MPM and to formulate a targeted approach based on the use of commercially available molecules, such as the multikinase inhibitor sorafenib and the mTOR inhibitor everolimus. METHODS: We planned a triple approach based on: i) analysis of immunophenotypes and mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No mutations were found in ‘hot spot’ regions of the mTOR upstream genes (e.g. EGFR, KRAS and PIK3CA). RESULTS: Phosphorylated mTOR and ERM were specifically overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination was effective in mTOR and ERM blockade; exerted synergistic effects on the inhibition of MPM cell proliferation; triggered ROS production and consequent AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally administered to MPM-bearing NOD/SCID mice. CONCLUSIONS: ERM and mTOR pathways are activated in MPM and ‘druggable’ by a combination of sorafenib and everolimus. Combination therapy is a promising therapeutic strategy against MPM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1363-1) contains supplementary material, which is available to authorized users