Il ruolo della Cassa Depositi e Prestiti nella prospettiva degli investimenti strategici di lungo periodo.

Il lavoro ha l’obiettivo di illustrare il compito della Cassa Depositi e Prestiti nel finanziare gli investimenti strategici in un’ottica di lungo periodo. All’interno del primo capitolo si ripercorre l’evoluzione storica della Cassa negli ultimi 160 anni ed il rapporto con le Fondazioni bancarie. Nel secondo capitolo, invece, dopo una breve definizione di infrastruttura, sono stati analizzati i vari strumenti che la Cassa adopera per i finanziamenti infrastrutturali, suddividendoli tra capitale di debito, fondi di private equity e partecipazioni strategiche. Grande importanza è stata data al ruolo della Cassa a livello europeo, sottolineato anche dalla partecipazione al Piano Juncker ideato con l’intento di rilanciare la crescita economica e produrre investimenti senza incrementare il debito pubblico. Infine, nel terzo capitolo si è analizzata l’infrastruttura portuale e logistica italiana, evidenziando punti di forza, di debolezza e i contatti con la Cassa Depositi e Prestiti

Ptaquiloside, the major carcinogen of bracken fern, in the pooled raw milk of healthy sheep and goats: an underestimated, global concern of food safety

Bracken fern (Pteridium aquilinum) is a worldwide plant containing toxic substances, which represent an important chemical hazard for animals, including humans. Ptaquiloside, 1, a norsesquiterpenoid glucoside, is the major carcinogen of bracken detected in the food chain, particularly in the milk from farm animals. To date, ptaquiloside has been shown in the milk of cows feeding on a diet containing bracken fern. This is the first study that shows the systematic detection of ptaquiloside, 1, and reports its direct quantitation in pooled raw milk of healthy sheep and goats grazing on bracken. Ptaquiloside, 1, was detected by a sensitive method based on the chemical conversion of ptaquiloside, 1, into bromopterosine, 4, following gas chromatography–mass spectrometry (GC–MS) analysis. The presence of ptaquiloside, 1, possibly carcinogenic to humans, in the milk of healthy animals is an unknown potential health risk, thus representing a harmful and potential global concern of food safety

Role of prophylactic central compartment lymph node dissection in clinically N0 differentiated thyroid cancer patients: Analysis of risk factors and review of modern trends

In the last years, especially thanks to a large diffusion of ultrasound-guided FNBs, a surprising increased incidence of differentiated thyroid cancer (DTC), "small" tumors and microcarcinomas have been reported in the international series. This led endocrinologists and surgeons to search for "tailored" and "less aggressive" therapeutic protocols avoiding risky morbidity and useless "overtreatment". Considering the most recent guidelines of referral endocrine societies, we analyzed the role of routine or so-called prophylactic central compartment lymph node dissection (RCLD), also considering its benefits and risks. Literature data showed that the debate is still open and the surgeons are divided between proponents and opponents of its use. Even if lymph node metastases are commonly observed, and in up to 90 % of DTC cases micrometastases are reported, the impact of lymphatic involvement on long-term survival is subject to intensive research and the best indications of lymph node dissection are still controversial. Identification of prognostic factors for central compartment metastases could assist surgeons in determining whether to perform RLCD. Considering available evidence, a general agreement to definitely reserve RCLD to "high-risk" cases was observed. More clinical researches, in order to identify risk factors of meaningful predictive power and prospective long-term randomized trials, should be useful to validate this selective approach

Single center experience with laparoscopic adrenalectomy on a large clinical series

BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard technique for the treatment of benign small and medium size adrenal masses (<6 cm), due to low morbidity rate, short hospitalization and patient rapid recovery. The aim of our study is to analyse the feasibility and efficiency of this surgical approach in a broad spectrum of adrenal gland pathologies. METHODS: Pre-operative, intra-operative and post-operative data from 126 patients undergone laparoscopic adrenalectomy between January 2003 and December 2015 were retrospectively collected and reviewed. Diagnosis was obtained on the basis of clinical examination, laboratory values and imaging techniques. Doxazosin was preoperatively administered in case of pheochromocytoma while spironolactone and potassium were employed to treat Conn's disease. Laparoscopic adrenalectomies were all performed by the same surgeon (CG). First 30 procedures were considered as learning curve adrenalectomies. RESULTS: One hundred twenty-six patients were included in the study. Functioning tumors were diagnosed in 84 patients, 27 patients were affected by pheochromocytomas, 29 by Conn's disease, 28 by Cushing disease. Surgery mean operative time was 137.33 min (range 100-180) during the learning curve adrenalectomies and 96.5 min (range 75-110) in subsequent procedures. Mean blood loss was respectively 160.2 ml (range 60-280) and 90.5 ml (range 50-200) in the first 30 procedures and the subsequent ones. Only one conversion to open surgery occurred. No post-operative major complications were observed, while minor complications occurred in 8 patients (0,79%). In 83 out of 84 functioning neoplasms, laparoscopic adrenalectomy was effective in normalization of endocrine profile. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and feasible procedure, even for functioning masses and pheochromocytomas. A multidisciplinary team including endocrinologists, endocrine surgeons and anaesthesiologists, is recommended in the management of adrenal pathology, and adrenal surgery should be performed in referral high volume centers. A thirty-procedures learning curve is recommended to improve surgical outcomes

and clinical aspect of lymphocytic hypophysitis

A B S T R A C T LYH (lymphocytic hypophysitis) is an autoimmune disease of the pituitary gland which can present with varying degrees of pituitary hormonal impairment and/or with symptoms related to pituitary enlargement. In this review, we provide an overview of the epidemiology, diagnosis, pathogenesis, treatment, and the role of organ-specific and antipituitary antibodies as potential markers of LYH. In addition, although the mechanisms underlying LYH are not completely understood, the role of prolactin, which plays an important part in maintaining immune system homoeostasis and is increased in the disease, is considered

Plasmodium transmission blocking activities of Vernonia amygdalina extracts and isolated compounds

BACKGROUND: Medicinal plants are a validated source for discovery of new leads and standardized herbal medicines. The aim of this study was to assess the activity of Vernonia amygdalina leaf extracts and isolated compounds against gametocytes and sporogonic stages of Plasmodium berghei and to validate the findings on field isolates of Plasmodium falciparum. METHODS: Aqueous (Ver-H2O) and ethanolic (Ver-EtOH) leaf extracts were tested in vivo for activity against sexual and asexual blood stage P. berghei parasites. In vivo transmission blocking effects of Ver-EtOH and Ver-H2O were estimated by assessing P. berghei oocyst prevalence and density in Anopheles stephensi mosquitoes. Activity targeting early sporogonic stages (ESS), namely gametes, zygotes and ookinetes was assessed in vitro using P. berghei CTRPp.GFP strain. Bioassay guided fractionation was performed to characterize V. amygdalina fractions and molecules for anti-ESS activity. Fractions active against ESS of the murine parasite were tested for ex vivo transmission blocking activity on P. falciparum field isolates. Cytotoxic effects of extracts and isolated compounds vernolide and vernodalol were evaluated on the human cell lines HCT116 and EA.hy926. RESULTS: Ver-H2O reduced the P. berghei macrogametocyte density in mice by about 50% and Ver-EtOH reduced P. berghei oocyst prevalence and density by 27 and 90%, respectively, in An. stephensi mosquitoes. Ver-EtOH inhibited almost completely (>90%) ESS development in vitro at 50 μg/mL. At this concentration, four fractions obtained from the ethylacetate phase of the methanol extract displayed inhibitory activity >90% against ESS. Three tested fractions were also found active against field isolates of the human parasite P. falciparum, reducing oocyst prevalence in Anopheles coluzzii mosquitoes to one-half and oocyst density to one-fourth of controls. The molecules and fractions displayed considerable cytotoxicity on the two tested cell-lines. CONCLUSIONS: Vernonia amygdalina leaves contain molecules affecting multiple stages of Plasmodium, evidencing its potential for drug discovery. Chemical modification of the identified hit molecules, in particular vernodalol, could generate a library of druggable sesquiterpene lactones. The development of a multistage phytomedicine designed as preventive treatment to complement existing malaria control tools appears a challenging but feasible goal

Sector-specific development and policy vulnerability in the Philippines

Ministry of Education, Singapore under its Academic Research Funding Tier

Isolation and structural elucidation of bioactive secondary metabolites from marine and terrestrial organisms

Natural products have historically been a rich source of "lead compounds" in drug discovery. The investigation of terrestrial plants and marine organisms aimed at searching new biologically active compounds is a central issue of this kind of studies, through structure elucidation combined with biological evaluation. My research work, described in this PhD thesis, falls within this research field and was addressed at three different topics: - i) isolation and structural elucidation of cytotoxic macrolides and depsipeptides and sterols active on PXR receptors from sponge Theonella swinhoei; ii) isolation and structural elucidation of metabolites modulating kinase activity from sponge Iotrochota purpurea; iii) isolation and analysis of correlation between reactivity and bioactivity for antimalarial and antinflammatory metabolites from the African plant Vernonia amygdalina. The structure elucidation of new molecules was performed using advanced spectroscopic techniques (2D-NMR and MS) and advanced methods of stereochemical determination (Murata's method and Marfey's method). The chemical investigation of spongal metabolites carried out during my PhD was financed by the European project "Bluegenics". Several structurally interesting bioactive molecules have been isolated from Theonella sp., namely swinholides (cyclic 44-member macrolides) and theonellapeptolides (cyclic tridecadepsipeptides with a large amount of non-ribosomial amino acids), both featuring in vitro antiproliferative activity and providing important information regarding structure-activity relationship. The class of 4-methylensterols, typical of Theonella sponges, showed activity on nuclear receptor PXR, shedding light on structure-activity relationships useful for synthesis of lead compunds to be used for therapy of metabolic diseases. Regarding the second topic, the isolation of haloindole derivatives, by bioguided approach, allowed their evaluation for antikinase activity, which could have an important impact on the manipulation of cell proliferation, diabetes, and neurodegenerative disorders. Finally, a bioguided analysis of Vernonia amygdalina, a plant from Africa used as foodstuff and as drugs in the folk medicine, allowed the characterization of plant extracts for stage specific effects on gametocytes and sporogonic stages of Plasmodium and identification of compounds responsible for antimalarial activity. In particular, leaves of V. amygdalina contain sesquiterpenes lactones vernolide and vernodalol featuring this kind of activity; thus, they have a potential for drug discovery and for the development of standardized V. amygdalina based phytomedicines. The second aim of the investigation on V. amygdalina was the isolation and structural elucidation of a series of sesquiterpenes compounds with Michael related bioactivity, capable of shedding light on the molecular mechanisms underlying the anti-inflammatory and anticancer activities detected for the extract. On these series, cysteamine assay proved to be a tool to build a sort of Michael-oma profile of this class of metabolites, identifying the most reactive site in polyfunctional compounds and ranking them in terms of reactivity. Considering the correlation between thia-Michael acceptor reactivity and modulation of important biological target, sesquiterpene lactones were evaluated on transcription factors NF-κB, STAT3 and Nrf2 involved in cancer initiation and progression, concluding that vernolide is the major anti-inflammatory constituent of extracts and elucidating the anticancer activity reported

Antibacterial and antioxidant constituents of Acaplypha wilkesiana.

This study was aimed at characterising the secondary metabolites responsible for antibacterial and antioxidant activities of Acalypha wilkesiana. Purification of the defatted methanol leaves extract was guided by the DPPH free radical scavenging assay as well as by evaluation of the antibacterial activity against four bacterial strains. As a result, geraniin, corilagin, quadrangularic acid M and shikimic acid were purified and isolated. Shikimic acid, reported for the first time from this plant, proved to be the major metabolite of the extract. All the four isolated compounds showed bactericidal activity against extended spectrum beta-lactamase-producing Klebsiella pneumoniae (700603), while corilagin was the single compound to exhibit antioxidant activity (IC50 53 μg/mL)