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Aims In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario. Materials and methods Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03. Results After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09–5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17–6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52–14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity. Conclusion Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach.

Telzenac® (Eltenac; 0.5 mg kg−1) was administered intravenously to two thoroughbred horses. After initial alkaline saponification followed by enzymolysis of the urinary phase II conjugates, the combined unconjugated compounds and aglycones were isolated by mixed mode solid phase extraction (SPE). The acidic isolate was either methylated or silylated (trimethylsilyl ether, TMS) and analysed by positive ion electron ionisation gas chromatography-mass spectrometry (GC-EI+-MS). Eltenac and two isobaric metabolites, hydroxyeltenac (aromatic oxidation) and eltenac sulfoxide were tentatively identified. Base peaks in the EI+ spectra of underivatised, methylated and TMS derivatised eltenac are formed by an initial loss of H2O, CH3OH or (CH3)3-Si-OH respectively, followed by successive losses of a chlorine atom and a carbonyl group. Similar fragmentation patterns were observed for the methyl and TMS derivatives of the two metabolites. Triamcinolone acetonide was used as the internal marker for the semi-quantification of eltenac. Selected samples were base-hydrolysed and extracted on-line on a C2 SPE column using a Prospekt sample handler. The retained analytes were eluted directly on to an analytical LC column and analysed by high performance liquid chromatography positive ion atmospheric pressure chemical ionisation MS in the selective ion recording mode. Most of the drug was excreted in less than 24 h. However it could still be detected in urine by full-scan GC-EI+-MS for over 96 h.

An innovative approach has been employed for the realization of bioactive scaffolds able to mimic the in vivo cellular microenvironment for tissue engineering applications. This method is based on the combination of molecular imprinting and soft-lithography technology to enhance cellular adhesion and to guide cell growth and proliferation due to presence of highly specific recognition sites of selected biomolecules on a well-defined polymeric microstructure. In this article polymethylmethacrylate (PMMA) scaffolds have been realized by using poly(dimethylsiloxane) (PDMS) microstructured molds imprinted with FITC-albumin and TRITC-lectin. In addition gelatin, an adhesion protein, was employed for the molecular imprinting of polymeric scaffolds for cellular tests. The most innovative aspect of this research was the molecular imprinting of whole cells for the development of substrates able to enhance the cell adhesion processes.

Two different molecularly imprinted polymers (MIP1 and MIP2) in the form of submicron-particles were obtained by radical polymerization, using acetonitrile as a solvent, methacrylic acid (MAA) as a functional monomer, a cross-linking agent (trimethylolpropane trimethacrylate (TRIM) for MIP1 and pentaerythritol triacrylate (PETRA) for MIP2) and phenylalanine aminoacid (Phe) as a template molecule. The extraction of Phe template from polymer submicron-particles by washing steps allowed the formation of free recognition sites for the selective rebinding of template molecule. Rebinding ability was evaluated in acetonitrile and in phosphate buffered saline by chromatographic methods and compared to that of corresponding control polymers. As MIP1 showed a superior specificity towards Phe rebinding as compared to MIP2, it was selected as a component of a poly( l -lactic acid) (PLLA) based model sensor-scaffold. Impedance measurements, carried out on PLLA films loaded with as-produced, extracted or rebound MIP1 submicron-particles demonstrated the possibility to build a scaffold capable of sensing the amount of rebound template. In the future, devices incorporating MIP submicron-particles able to rebind extracellular matrix or transmembrane proteins will be respectively used as structures promoting cell adhesion and proliferation and sensor-films monitoring cell colonization.

Summary Objective: In randomized clinical trials, aldosterone antagonists have been shown to reduce mortality and morbidity in heart failure (HF). The aim of the present study was to examine the risk-benefit profile of aldosterone antagonists in routine clinical practice. Methods: A retrospective analysis, extending over a 1-year period, of the clinical, instrumental and laboratory data of 264 HF outpatients was performed. All patients were on a β-blocker and an ACE-inhibitor (or angiotensin-II receptor-blocker) and 151 were taking an aldosterone antagonist. Results: At baseline, subjects treated with aldosterone antagonists had a higher NYHA class, a larger left-ventricular end-diastolic volume, a worse ejection fraction and a higher systolic pulmonary arterial pressure (sPAP). During follow-up, a greater reduction in sPAP and a tendency towards improved systolic and diastolic function were observed in subjects treated with aldosterone antagonists. Moreover, clinical and laboratory parameters did not deteriorate in patients taking aldosterone antagonists. Mortality rates were similar in the two groups (8·6% vs. 8·8%, P = NS). Conclusions: The use of aldosterone antagonists in HF is associated with an improvement in cardiac function and is well tolerated. In the present study, patients administered these agents had a comparable clinical outcome to that of the control group, despite important differences in baseline risk.

A simple and rapid method is reported for the routine determination 1-phenylazo-2-naphthol (Sudan I) in chilli powder and in chilli-containing food products. The method involved Soxtec extraction from the products followed by high-pressure gel permeation chromatographic clean-up collecting the appropriate fraction. Analysis of this fraction was by HPLC with UV/VIS detection. The limit of detection was 7 microg kg(-1) and the limit of quantification was 13 microg kg(-1). The identity of Sudan I in food products was established by electrospray LC/MS with MS/MS confirmation. From a small survey of 30 retail samples, 11 samples of crushed chilli, Italian pasta, chilli-snack and vegetable sauce contained levels of Sudan I ranging from 24 to 5591 microg kg(-1).

The recruitment of monocyte-derived macrophages (MDMs) and arterial smooth muscle cells (ASMCs) contributes to inflammation and development of intimal hyperplasia during atherosclerosis. Platelet-derived growth factor (PDGF) is a potent mitogen for SMC, signalling through PDGF-receptor subunits alpha (Ralpha) and beta (Rbeta). We have previously found that interferon gamma (IFNgamma) upregulates PDGF-Ralpha mRNA expression in human MDM (hMDM) which causes an increased migration towards PDGF. In the present study, we found that IFNgamma mediated an upregulation of PDGF-Ralpha mRNA also in THP-1 cells. The induction of PDGF-Ralpha in both hMDM and THP-1 cells was caused by STAT1 binding to the PDGF-Ralpha promoter. In human ASMCs, IFNgamma again stimulated a transient STAT1-binding to the PDGF-Ralpha promoter. However, this was not followed by an upregulation of PDGF-Ralpha mRNA. IFNgamma-stimulation resulted in augmented expression of PDGF-Ralpha protein in differentiated hMDM. Early hMDM only expressed an immature and not fully glycosylated form of the PDGF-Ralpha protein. In contrast, THP-1 cells did not synthesize PDGF-Ralpha protein, implying further posttranscriptional inhibition. Our results contribute to a better understanding of the complex regulation of PDGF-Ralpha expression and how proinflammatory factors may contribute to PDGF-related hyperplasia in vascular diseases.

A sensitive, specific and robust liquid chromatography-mass spectrometry (LC-MS) method for the determination of fluconazole (α-(2,4-difluorophenyl)-α-(1H-1,2,4-triazol-1-ylmethyl)-1H-1,2,4-triazole-1-ethanol) in human plasma has been developed and validated. HPLC-UV detection lacked sensitivity and GC-MS analysis was hindered by excessive injection carry-over. The method was successfully developed and validated over a range of 50 ng.mL−1 to 4000 ng.mL−1 using protein precipitation. Deuterated fluconazole (d5) was synthesised ‘in-house’ and used as the LC-MS internal standard. This method has been successfully used to support a bioequivalence clinical study.

This paper presents extensive results of training architectures of one- and two- hidden-layer, fully connected, feedforward neural networks which are used for handwritten digit recognition. Both architectures include 1 to 400 units in each hidden layer to produce a series of 112 networks. These networks are trained by backpropagation up to 1000 iterations and tested while advancing in training. Results are presented as a function of the number of hidden units, the number of iterations, and the training mode (centered and position-shifted patterns). An overall maximum recognition rate of 92.4% is obtained for a two-hidden layer network with 100 hidden units and 144 iterations. No significative recognition rate improvement is achieved (within 2.1 percentage points) by increasing the number of hidden units and iterations above 50 and 30, respectively.

A crude extract of Caulerpa taxifolia was tested for its antiviral activity. The chloroform-methanol residue showed an interesting inhibitor effect in vitro toward the feline immunodeficiency virus (FIV), a valid model for studying the acquired immunodeficiency syndrome. This extract reduced the virus-induced syncytia in the cultured cells, the viral reverse transcriptase activity and the viral capsid protein P24 expression.

Lavandula angustifolia Miller essential oil and some of its main constituents, i.e. linalool, linalyl acetate, and camphor were tested in vitro for their bioactivities against Psoroptes cuniculi (Delafond, 1859), mite of the rabbit. The essential oil and linalool were found to have very powerful miticidal activities.

Water of a recreational zone of the Río de la Plata was analyzed. Levels of total heterotrophic bacteria ranged from 1.5 x 10(3) to 6.2 x 10(3) CFU/ml and total coliforms were between 5.0 x 10(2) and 7.0 x 10(3) per 100 ml. Values of fecal coliforms were between 1.0 x 10(2) and 1.3 x 10(3) per 100 ml. Among 131 E. coli strains isolated, 20.6% of cephalothin resistance was found, followed by nitrofurantoin, ampicillin, sulfisoxazole and the trimethoprim sulfamethoxazole combination. Resistance to more than one antibiotic was found in 36.7% of the strains isolated and 9.2% were resistant to three or more antibiotics. Three strains resistant to four antibiotics and one resistant to five were isolated. The highest percentage of combined resistance occurred for the pairs cephalothin-nitrofurantoin and cephalothin-ampicillin.

A case of a congenital aneurysm of the extrahepatic portal vein is reported. It was complicated by segmental portal hypertension of the territory of the inferior mesenteric vein, which was a pathway for spontaneous porto-caval shunting.

To determine the function of VEGF-A in nervous system development, we have utilized the Nestin promoter-driven Cre recombinase transgene, in conjunction with a conditional and hypomorphic VEGF-A allele, to lower VEGF-A activity in neural progenitor cells. Mice with intermediate levels of VEGF-A activity showed decreased blood vessel branching and density in the cortex and retina, resulting in a thinner retina and aberrant structural organization of the cortex. Severe reductions in VEGF-A led to decreases in vascularity and subsequent hypoxia, resulting in the specific degeneration of the cerebral cortex and neonatal lethality. Decreased neuronal proliferation and hypoxia was evident at E11.5, leading to increased neuronal apoptosis in the cortex by E15.5. In order to address whether the observed changes in the structural organization of the nervous system were due to a direct and autocrine role of VEGF-A on the neural population, we conditionally inactivated the main VEGF-A receptor, Flk1, specifically in neuronal lineages, by using the Nestin Cre transgene. The normality of these mice ruled out the possibility that VEGF-A/Flk1 signaling has a significant autocrine role in CNS development. VEGF-A dosage is therefore a critical parameter regulating the density of the vascular plexus in the developing CNS that is in turn a key determinant in the development and architectural organization of the nervous system.

Surgical correction of stenosing lesions of the extracranial cerebral arteries, responsible for reduced encephalic perfusion, may prevent neurological damage, even when there is bilateral involvement of carotid arteries (stenosis + obstruction). Moreover in these patients poor haemodynamical conditions are thought to be responsible for high perioperatory neurological morbidity and mortality. From case histories with no mortality and low neurological morbidity, other authors state that revascularization of a stenotic carotid artery may be carried out with a reasonable safety margin, even when there is an obstructive lesion of the contralateral carotid artery. On the basis of the 64 cases of revascularization carried out in patients with obstructions of an internal carotid artery associated with a stenotic lesion of the contralateral, we have made a survey of the results, indications and possibilities of treatment in these patients.

The experience with ruptured aneurysms of the abdominal aorta is reported. Out of 395 aneurysms observed, 78 were ruptured. A review of case histories and an analysis of the causes of death demonstrate the importance of prompt diagnosis and early operation: delay and the use of complicated (TC) or invasive (angiography) instrumental examinations does not appear justified since clinical symptoms, plain standard abdominal films and ultrasound almost always lead to prompt diagnosis. Notwithstanding the improvements in resuscitation and intensive care procedures, a significant difference persists between the mortality rate of elective surgery (3 to 8%) and that of emergency surgery. There were 28 deaths (36%) for emergency surgery as against 3.4% for operations performed for non-ruptured aneurysms. This confirms the need for preventive treatment of aneurysmal lesions of the abdominal aorta, since even aneurysms smaller than 5 cm may rupture.

Molecular imprinting is an emerging technology that allows to introduce nanostructured cavities into a polymer. In preparing molecular imprinted polymers (MIPs), the functional monomer(s) is first prearranged around the template molecule by specific interactions; the polymerisation is then carried out with a high percentage of cross-linking agent (which “freezes” the macromolecular network). Molecular mechanics and dynamics can be used to gain indications on the best monomers to be used in order to maximize interactions with the template. Once the polymerization reaction has been completed, the template is removed from the rigid three-dimensional network, leaving free recognition cavities available for the successive selective rebinding of the template itself. Precipitation polymerisation in dilute solutions involves the spontaneous formation of submicron scale polymer particles, which result suitable for recognition-rebinding application. Therapeutic applications: The recognition mechanism by MIPs relies mainly on the establishment of reversible hydrogen bonding interactions. It is clear that the efficiency of this mechanism is endangered in aqueous environments. MIPs working in water solutions are clearly of great interest in the medical and food industry and in sensor applications. We recently overcame these difficulties by the realisation of a system where cross-linked MI methylmethacrylate-methacrylic acid nanospheres where loaded on the surface or inside the matrix of porous membranes created by phase inversion. E.g. membranes were modified by adding cholesterol imprinted nanoparticles. Rebinding performances of nanoparticles modified membranes in buffer solution were tested showing a specific recognition of 14.09 mg of cholesterol/g of system (membrane and nanoparticles), indicating maintained binding capacity of supported particles as well. Tissue engineering: The engineering of functionalised polymeric structures for the study of cell activity is essential to the development of biological substitutes containing vital cells capable of regenerating or enhancing tissue function. Cells are organised within a complex matrix consisting of high molecular weight protein and polysaccharides known as the Extracellular Matrix (ECM). Two approaches are described to explore the possibility to provide scaffolds with specific and selective recognition of peptide sequences or proteins involved in cell adhesion mechanisms: one approach consists in the modification of porous structures with nanoparticles imprinted with aminoacid sequences (epitopes) of ECM proteins or transmembrane integrins, while the other consists in the combination of Soft Litography and Molecular Imprinting technologies (SOFT-MI). This technology allows to create imprinting nanocavities selective towards ECM proteins in microfabricated scaffolds, and in particular it permits to realise patterns with a well defined microscale geometry in polymethylmethacrylate (PMMA) scaffolds providing them with cell adhesion properties that were missing in the non-imprinted scaffold.Copyright © 2006 by ASME

Fractionation of the light petroleum extract of the aerial parts of Carduus getulus Pomel afforded, in addition to taraxasterol acetate and taraxasterol, erythrodiol 3-acetate which has never been reported in the Compositae before.

Analizzando il complesso della documentazione archeologica attualmente nota, il presente contributo si propone di formulare alcune osservazioni intorno al ruolo (eventualmente) svolto dagli atelier monetali nella produzione dei piatti di largizione distribuiti in occasione dei quinquennalia di Licinio II Cesare (321 d.C.).

Il contributo, prendendo l’avvio dal contesto di rinvenimento e dai primi studi condotti sulla cosiddetta patera di Rennes, si incentra sull’analisi della decorazione che caratterizza il prezioso manufatto aureo, rinvenuto fortuitamente a Rennes (Bretagna) nel 1774 e oggi conservato presso il Département des Monnaies, médailles et antiques della Bibliothèque nationale de France (inv. 56-94). Nell’intento di interpretare il significato simbolico sotteso alla natura e alle caratteristiche estrinseche del reperto, lo studio analizza, in particolare, l’apparato decorativo monetale, costituito da sedici aurei, incastonati nella fascia più esterna dell’oggetto. Partendo dalla catalogazione delle singole monete, l’indagine procede con un esame di tipo formale, evidenziando come la successione degli esemplari - tutti esposti tramite il lato di dritto, recante l’effigie di personaggi maschili e femminili della dinastia antonino-severiana - non segua l’ordine cronologico delle emissioni (da Adriano a Geta), ma scandisca una sequenza preordinata, ripetuta quattro volte. In questo senso, l’ordine effettivo degli esemplari appare individuato dall’alternanza dei ritratti monetali dei membri della domus imperiale, disposti secondo lo schema Augusto senior-Augusto iunior o Cesare-Augusto senior-Augusta. Lo studio, condotto attraverso un’analisi minuziosa, ha rilevato l’esistenza di un impianto concepito meticolosamente in relazione non solo alla scelta, ma anche alla predisposizione delle monete, determinato dal preciso intento di creare collegamenti e richiami ricorrenti tra i personaggi raffigurati, nell’ottica della ricostruzione dei legami di legittimazione della successione imperiale. Le monete d’oro reimpiegate nella decorazione della patera evidenziano, dunque, la costruzione di un vero e proprio percorso ideologico, finalizzato alla celebrazione della dinastia severiana, consolidatasi attraverso la procedura di autoadozione all’interno della domus antonina promossa da Settimio Severo.

Pur comportando funzioni e significati specifici diversi, i manufatti di gioielleria monetale manifestano una valenza ideologica strettamente connessa alla celebrazione dell’istituzione imperiale, derivante dall’esibizione del ritratto monetale di personaggi maschili e femminili della domus Augusta. In questa prospettiva, considerando l’ambito cronologico compreso tra la prima e la media età imperiale, il presente contributo si propone di raccogliere le occorrenze del ritratto femminile raffigurato su monete reimpiegate nella realizzazione di gioielli utilizzati come oggetti di ornamento personale.

The topical anti-inflammatory activity of the ethanol and aqueous extracts from the aerial parts of Lavandula multifida L. (Lamiaceae), used in the Moroccan traditional medicine, was investigated by inhibition of the Croton oil-induced ear edema in mice. The biological assay revealed a dose-dependent anti-inflammatory activity for the ethanol extract, while the aqueous one was less active. Bioassay-guided fractionation of the ethanol extract led to identify four triterpenic acids of oleanane series, four pimarane and one iso-pimarane diterpenes, as well as the phenolic monoterpene carvacrol and its glucoside. Some of these compounds revealed an anti-inflammatory activity comparable to that of indomethacin.