Metal Tolerance Capability of Helichrysum microphyllum Cambess. subsp. tyrrhenicum Bacch., Brullo & Giusso: A Candidate for Phytostabilization in Abandoned Mine Sites.

Sardinia was known as an important mine pole in Europe during his history. Still after decades from mine closure, 75.000.000 m3 of mine waste, rich in heavy metals, were left abandoned causing a huge environmental legacy on the mine district area. Consequently, cost effective remediation is required. In this frame, phytoremediation is considered a feasible candidate. This research was focused on Helichrysum microphyllum subsp. tyrrhenicum, which is pioneer in xeric soils with low-functions, like mine tailings. The aim of this study was to evaluate its ability to extract heavy metals from mine soils and accumulate them in plant tissues and its suitability for phytostabilization. Sundry samples of soil, roots and epigean organ were collected through field sampling and analysed in order to obtain metals concentration and mineralogical characteristics. Our results indicate that this species tolerates high concentration of zinc, lead and cadmium, behaving as a species suitable for phytostabilization.

Evaluation of antimicrobial activity of Italian honey for wound healing application in veterinary medicine.

INTRODUCTION: Honey as a topical treatment for infected wounds dates back to ancient times. However, few studies have been reported concerning the medical properties of Italian honey. In this study, the microbial contamination, the antimicrobial activity and the antibiotic residues of 6 different varieties of Piedmont honeys were evaluated. The antimicrobial activity of honeys was tested by agar well diffusion method and 1 honey for each variety has been selected and tested by broth micro-dilution test to determine Minimum Inhibitory Concentrations (MICs) and evaluated by Minimum Bactericidal Concentrations (MBCs). The honeys with a high level of antibacterial activity were analyzed for the presence of tetracyclines, sulfonamides and macrolide residues. The agar well diffusion method showed the greatest antimicrobial activity for honeydew, chestnut and lime tree honeys. The MICs and MBCs identified the close similarity to the medical manuka honey of honeydew, polyfloral and chestnut honey. The levels of antibiotic residues on these honeys were below the limit of quantification. Based on our results the Italian variety of honeydew showed the best antimicrobial activity and can be considered for the treatment of infected wounds in animals.

INTRODUCTION: L'utilisation du miel pour le traitement des plaies infectées remonte à loin dans l'antiquité. Dans le présent travail, on étudie les contaminations microbiennes, l'activité antimicrobienne et les résidus d'antibiotiques dans 6 sortes de miels différentes provenant du Piémont. L'activité antimicrobienne a été mesurée au moyen d'une méthode de diffusion sur gel d'agar et un échantillon de chaque sorte de miel a été examiné quant à sa concentration minimale inhibitrice (CMI) et sa concentration minimale bactéricide (CMB) au moyen d'un test de micro-dilution. Les échantillons présentant une haute activité antibactérienne ont été analysés quant à la présence de tétracycline, de sulfamidés et de macrolides. Au test de diffusion sur agar, le miel de miellat ainsi que ceux de châtaignier et de tilleul ont démontré la plus grande activité antimicrobienne. Les CIM et CBM permettent de reconnaitre une grande similitude entre les miels de miellat, de nectar et de tilleul avec le miel de Manuka utilisé à des fins thérapeutiques. Les résidus d'antibiotiques de ces échantillons se situaient en dessous des limites de détection. Sur la base de ces constatations, les divers miels de miellat italiens présentent la plus grande activité antimicrobienne et peuvent être utilisés pour le traitement de plaies infectées chez les animaux.

Effect of the neuropeptides vasoactive intestinal peptide, peptide histidine methionine and substance P on human major salivary gland secretion.

OBJECTIVE: The parasympathetic transmitters vasoactive intestinal peptide (VIP) and substance P (SP) are secretagogues in salivary glands of animals. Currently, we hypothesise that in human salivary glands, these neuropeptides and the VIP-related peptide histidine methionine (PHM) also exert secretory actions, reflected morphologically by exocytosis of acinar protein/glycoprotein-storing granules. MATERIALS AND METHODS: Submandibular and parotid gland tissues, exposed in vitro to VIP and PHM, and SP, respectively, were examined by light and transmission electron microscopy. For comparison, the response to in vitro stimulation of isoproterenol, phenylephrine and carbachol was examined. Moreover, the peptidergic innervation of the glands was examined by immunohistochemistry. RESULTS: Vasoactive intestinal peptide- and PHM-immunoreactive nerves were in close proximity to acini and ducts in the two glands, while these elements lacked a SP-positive innervation. While no morphological changes occurred in response to SP (parotid glands), VIP and PHM administration (submandibular glands) caused conspicuous acinar degranulation accompanied by luminal space broadening. In the two glands, both α1 - and ß-adrenergic receptor stimulation and muscarinic receptor stimulation caused similar changes as to VIP/PHM, although to varying extent. CONCLUSIONS: Vasoactive intestinal peptide and PHM, but not SP, are likely transmitters in the parasympathetic control of salivary (protein) secretion in humans.

A new method for determining the sources of airborne particles.

Air quality is a major issue for humans owing to the fact that the content of particles in the atmosphere has multiple implications for life quality, ecosystem dynamics and environment. Scientists are therefore particularly interested in discovering the origin of airborne particles. A new method has been developed to model the relationship between the emission surface and the total amount of airborne particles at a given distance, employing olive pollen and olive groves as examples. A third-degree polynomial relationship between the air particles at a particular point and the distance from the source was observed, signifying that the nearest area to a point is not that which is most correlated with its air features. This work allows the origin of airborne particles to be discovered and could be implemented in different disciplines related to atmospheric aerosol, thus providing a new approach with which to discover the dynamics of airborne particles.

Bone regeneration in a rabbit critical femoral defect by means of magnetic hydroxyapatite macroporous scaffolds.

Magnetic scaffolds have recently attracted significant attention in tissue engineering due to the prospect of improving bone tissue formation by conveying soluble factors such as growth factors, hormones, and polypeptides directly to the site of implantation, as well as to the possibility of improving implant fixation and stability. The objective of this study was to compare bone tissue formation in a preclinical rabbit model of critical femoral defect treated either with a hydroxyapatite (HA)/magnetite (90/10 wt %) or pure HA porous scaffolds at 4 and 12 weeks after implantation. The biocompatibility and osteogenic activity of the novel magnetic constructs was assessed with analysis of the amount of newly formed bone tissue and its nanomechanical properties. The osteoconductive properties of the pure HA were confirmed. The HA/magnetite scaffold was able to induce and support bone tissue formation at both experimental time points without adverse tissue reactions. Biomechanically, similar properties were obtained from nanoindentation analysis of bone formed following implantation of magnetic and control scaffolds. The results indicate that the osteoconductive properties of an HA scaffold are maintained following inclusion of a magnetic component. These provide a basis for future studies investigating the potential benefit in tissue engineering of applying magnetic stimuli to enhance bone formation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 546-554, 2018.

Cognition in multiple sclerosis: Between cognitive reserve and brain volume.

BACKGROUND: Several correlations between cognitive impairment (CI), radiologic markers and cognitive reserve (CR) have been documented in MS. OBIECTIVE: To evaluate correlation between CI and brain volume (BV) considering CR as possibile mitigating factor. METHODS: 195 relapsing MS patients underwent a neuropsychological assessment using BICAMS. BV was estimated using SIENAX to obtain normalized volume of brain (NBV), white matter (NWV), gray matter (NGV) and cortical gray matter (CGV). CR was estimated using a previously validated tool. RESULTS: Pearson test showed a correlation between the symbol digit modality test (SDMT) score and NBV (r=0.38; p<0.000) NGV(r=0.31; p<0.000), CGV (r=0.35; p<0.000) and CRI score(r=0.42; p<0.000). Linear regression (dependent variable:SDMT) showed a relationship with CR scores (p=0.000) and NGV(p<0.000). A difference was detected between cognitive impaired and preserved patients regarding mean of NBV(p=0.002), NGV(p=0.007), CGV(p=0.002) and CR Scores (p=0.007). Anova showed a association between the presence of CI (dependent variable) and the interaction term CRIQ × CGV (p=0.004) whit adjustment for age and disability evaluated by EDSS. CONCLUSIONS: Our study shows a correlation between cognition and BV, in particular gray matter volume. Cognitive reserve is also confirmed as an important element playing a role in the complex interaction to determine the cognitive functions in MS.

Effect of gluten-free diet and co-morbidity of irritable bowel syndrome-type symptoms on health-related quality of life in adult coeliac patients.

BACKGROUND: Both coeliac disease and irritable bowel syndrome show impaired health-related quality of life, however, the impact of irritable bowel syndrome-type symptoms on health-related quality of life in coeliac disease is unclear. AIM: To evaluate the effect of gluten-free diet adherence and irritable bowel syndrome-type symptoms co-morbidity on health-related quality of life in adult coeliac disease patients. PATIENTS AND METHODS: A total of 1130 adults were enrolled in the study comprising 1001 controls from the general population and 129 diagnosed coeliac disease patients from the University Clinic in Cagliari. Irritable bowel syndrome-type symptoms and health-related quality of life were assessed using the Rome II and the SF-36 questionnaires, respectively. RESULTS: Irritable bowel syndrome-type symptoms prevalence in controls was 10.1% (102/1001) and 55% (71/129) in the coeliac disease patients. Irritable bowel syndrome-type symptom controls and coeliac disease patients both presented significantly lower health-related quality of life (p

Effects of working gas pressure on zirconium dioxide thin film prepared by pulsed plasma deposition: roughness, wettability, friction and wear characteristics.

In joint arthroplasty one of the main issues related to the failure of prosthetic implants is due to the wear of the ultra-high molecular weight polyethylene (UHMWPE) component. Surface treatments and coatings have been recognized as enhancing methods, able to improve the tribological properties of the implants. Therefore, the main objective of this work was to investigate the possibility to fabricate yttria-stabilized zirconia (YSZ) coatings on a metal (AISI 316-L) substrate by means of Pulsed Electron Deposition, in order to improve the tribological behavior of the polymer-metal coupling, by reducing the initial wear of the UHMWPE component. In order to optimize the coating characteristics, the effects of working gas pressure on both its morphological and tribological properties were analyzed. Morphological characterization of the films was evaluated by Atomic Force Microscopy (AFM). Coating wettability was also estimated by contact angle (CA) measurement. Tribological performance (coupling friction and wear of UHMWPE) was evaluated by using a ball-on-disc tribometer during highly-stressing tests in dry and lubricated (i.e. NaCl and serum) conditions; friction and wear were specifically evaluated at the initial sliding distances - to highlight the main effect of coating morphology - and after 100m - where the influence of the intrinsic materials properties prevails. AFM analysis highlighted that the working pressure heavily affected the morphological characteristics of the realized films. The wettability of the coating at the highest and lowest deposition pressures (CA ~ 60°, closed to substrate value) decreased for intermediate pressures, reaching a maximum CA of ~ 90°. Regarding tribological tests, a strong correlation was found in the initial steps between friction coefficient and wettability, which decreased as the distance increased. Concerning UHMWPE wear associated to coated counterpart, at 100m a reduction rate of about 7% in dry, 12% in NaCl and 5% in presence of serum was obtained compared to the uncoated counterpart. Differently from what highlighted for friction, no correlation was found between wear rate and morphological parameters. These findings, in agreement with literature, underlined the effect of the deposition pressure on the morphological properties, but suggested that physical characteristics are influenced too. Further research on the deposition process will be required in order to improve the tribological performance of the coating at long distances, addressing - above all - orthopedic applications.

Emerging therapies provide new opportunities to reshape the multifaceted interactions between the immune system and lymphoma cells.

The acquisition of a complete neoplastic phenotype requires cancer cells to develop escape mechanisms from the host immune system. This phenomenon, commonly referred to as 'immune evasion,' represents a hallmark of cancers and results from a Darwinian selection of the fittest tumor clones. First reported in solid tumors, cancer immunoescape characterizes several hematological malignancies. The biological bases of cancer immunoescape have recently been disclosed and include: (i) impaired human leukocyte antigen-mediated cancer cell recognition (B2M, CD58, CTIIA, CD80/CD86, CD28 and CTLA-4 mutations); (ii) deranged apoptotic mechanisms (reduced pro-apoptotic signals and/or increased expression of anti-apoptotic molecules); and (iii) changes in the tumor microenvironment involving regulatory T cells and tumor-associated macrophages. These immune-escape mechanisms characterize both Hodgkin and non-Hodgkin (B and T cell) lymphomas and represent a promising target for new anti-tumor therapies. In the present review, the principles of cancer immunoescape and their role in human lymphomagenesis are illustrated. Current therapies targeting these pathways and possible applications for lymphoma treatment are also addressed.

Tribological characterization of zirconia coatings deposited on Ti6Al4V components for orthopedic applications.

One of the most important issues leading to the failure of total joint arthroplasty is related to the wear of the plastic components, which are generally made of ultra high molecular weight polyethylene (UHMWPE). Therefore, the reduction of joint wear represents one of the main challenges the research in orthopedics is called to address nowadays. Surface treatments and coatings have been recognized as innovative methods to improve tribological properties, also in the orthopedic field. This work investigated the possibility to realize hard ceramic coatings on the metal component of a prosthesis, by means of Pulsed Plasma Deposition, in order to reduce friction and wear in the standard coupling against UHMWPE. Ti6Al4V substrates were coated with a 2 µm thick yttria-stabilized zirconia (YSZ) layer. The mechanical properties of the YSZ coatings were assessed by nanoindentation tests performed on flat Ti6Al4V substrates. Tribological performance was evaluated using a ball-on-disk tribometer in dry and lubricated (i.e. with fetal bovine serum) highly-stressing conditions, up to an overall distance of 10 km. Tribology was characterized in terms of coefficient of friction (CoF) and wear rate of the UHMWPE disk. After testing, specimens were analyzed through optical microscopy and SEM images, in order to check the wear degradation mechanisms. Progressive loading scratch tests were also performed in dry and wet conditions to determine the effects of the environment on the adhesion of the coating. Our results supported the beneficial effect of YSZ coating on metal components. In particular, the proposed solution significantly reduced UHMWPE wear rate and friction. At 10 km of sliding distance, a wear rate reduction of about 18% in dry configuration and of 4% in presence of serum, was obtained by the coated group compared to the uncoated group. As far as friction in dry condition is concerned, the coating allowed to maintain low CoF values until the end of the tests, with an overall difference of about 40% compared to the uncoated balls. In wet conditions, the friction values were found to be comparable between coated and uncoated materials, mainly due to a premature delamination of the coating. Scratch tests in wet showed in fact a reduction of the critical load required to a complete delamination due to a formation of blister, although no change or damage occurred at the coating during the soaking period. Although conditions of high values of contact pressure were considered, further analyses are however required to fully understand the behavior of YSZ coatings in wet environment and additional research on the deposition process will be mandatory in order to improve the coating tribological performance at long distances addressing orthopedic applications.

Optimizing thickness of ceramic coatings on plastic components for orthopedic applications: A finite element analysis.

Realizing hard ceramic coatings on the plastic component of a joint prosthesis can be strategic for the mechanical preservation of the whole implant and to extend its lifetime. Recently, thanks to the Plasma Pulsed Deposition (PPD) method, zirconia coatings on ultra-high molecular weight polyethylene (UHMWPE) substrates resulted in a feasible outcome. Focusing on both the highly specific requirements defined by the biomedical application and the effective possibilities given by the deposition method in the perspectives of technological transfer, it is mandatory to optimize the coating in terms of load bearing capacity. The main goal of this study was to identify through Finite Element Analysis (FEA) the optimal coating thickness that would be able to minimize UHMWPE strain, possible insurgence of cracks within the coating and stresses at coating-substrate interface. Simulations of nanoindentation and microindentation tests were specifically carried out. FEA findings demonstrated that, in general, thickening the zirconia coating strongly reduced the strains in the UHMWPE substrate, although the 1 µm thickness value was identified as critical for the presence of high stresses within the coating and at the interface with the substrate. Therefore, the optimal thickness resulted to be highly dependent on the specific loading condition and final applications.

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.

Frontal cortical perfusion abnormalities related to gluten intake and associated autoimmune disease in adult coeliac disease: 99mTc-ECD brain SPECT study.

OBJECTIVE: Since brain perfusion abnormalities have been described by single-photon emission computed tomography in some autoimmune diseases, the aim of the present study was to evaluate the incidence of perfusion abnormalities by brain single-photon emission computed tomography in a group of coeliac disease patients, and to investigate whether gluten intake and associated autoimmune diseases may be considered risk factors in causing cerebral impairment. METHODS: Thirty-four adult coeliac patients (16 on a gluten-free diet and 18 on a gluten-containing diet, 18 (53%) with autoimmune diseases) underwent 99mTc-ethyl cysteinate dimer brain single-photon emission computed tomography and qualitative evaluation of brain perfusion was performed together with a semiquantitative estimation using the asymmetry index. Ten subjects on our database, matched for sex, age and ethnic group, who were proved normal by histology ofjejunal mucosa (four males and six females; median age 39 years, range 27-55 years), were included as control group. RESULTS: Twenty-four out of 34 patients (71%) showed brain single-photon emission computed tomography abnormalities confirmed by abnormal regional asymmetry index (>5%; range 5.8-18.5%). Topographic comparison of the brain areas showed that the more significant abnormalities were localised in frontal regions, and were significantly different from controls only in coeliac disease patients on unrestricted diet. The prevalence of single-photon emission computed tomography abnormalities was similar in coeliac disease patients with (74%) and without (69%) associated autoimmune disease. CONCLUSIONS: Abnormalities of brain perfusion seem common in coeliac disease. This phenomenon is similar to that previously described in other autoimmune diseases, but does not appear to be related to associated autoimmunity and, at least in the frontal region, may be improved by a gluten-free diet.

[Celiac disease in insulin-dependent diabetes mellitus and insulin-independent diabetes mellitus]. / Studio della malattia celiaca in corso di diabete mellito insulino dipendente e di diabete insulino indipendente.

The IgA antigliadin antibodies AGA title was detected in 37 patients with IDDM, mean age 32.59 +/- 14.71, where mean duration of disease was 8.76 +/- 9.62 years, and 29 patients with NIDDM, mean age 55.31 +/- 14.71, where disease lasted 11.5 +/- 5.55 years. A group of 51 normal pts. was employed as control. In IDDM group 2 cases on 37 showed high AGA title (case n. 1 and n. 2) but just the case n. 1 where IDDM lasted 16 years, showed an histologic picture of coeliac disease (partial villous atrophy), while in the case n. 2 where IDDM was at the onset, the histologic picture was normal. The increase of AGA title in the IDDM at the onset is rarely associated with coeliac disease, but it seems to be an aspecific response. Viceversa an increased AGA title is in IDDM for greater than 1 years often associated with coeliac disease. In NIDDM no high AGA title was found. The prevalence of coeliac disease in our patients with IDDM was 1:37 and we suggest that diabetics be screened routinely for antigliadin antibody.

Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established "chronic" schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.

Telomere length is an independent predictor of survival, treatment requirement and Richter's syndrome transformation in chronic lymphocytic leukemia.

Telomere length (TL) has been associated with outcome in chronic lymphocytic leukemia (CLL). The aim of this extensive analysis carried out on 401 CLL patients was to assess TL conclusively as a prognostic biomarker. Our study included two cohorts used as learning (191 patients) and blinded validation series (210 patients). A TL cutoff of 5000 bp was chosen by receiver operating characteristic (ROC) analysis and Youden's index in the learning series. In this series, TL< or =5000 bp was independently associated to a worse outcome for both overall survival (OS; 105.5 vs 281 months, P<0.001) and treatment-free survival (TFS; 24.6 vs 73 months, P<0.001). In the blinded validation series, TL< or =5000 bp was confirmed as an independent outcome predictor for OS (79.8 vs not reached, P<0.001) and TFS (15.2 vs 130.8 months, P<0.001). Moreover, TL< or =5000 bp independently predicted the risk of Richter's syndrome (5-year risk: 18.9 vs 6.4%, P=0.016). Within CLL subsets defined by biological predictors, TL consistently identified patient subgroups harboring unfavorable prognosis. These results demonstrate that TL is a powerful independent predictor of multiple outcomes in CLL, and contributes to refine the prognostic assessment of this disease when utilized in combination with other prognostic markers. We thus believe that this prognostic biomarker has the potential for a more widespread use in CLL.

Adult celiac disease is frequently associated with sacroiliitis.

No data are available on the presence and frequency of peripheral or central joint disease, routinely determined by bone scintigraphy with 740 MBq of [99mTc]MDP, in adult celiac disease. Bone scintigraphy was carried out to detect early acute inflammatory lesions in 22 adult celiac patients (15 females and seven males; mean age 36.72 years, range 17-63). Bone scintigraphy was positive for sacroiliitis in 14 cases (63.6%). Except in the case of one patient suffering from rheumatoid arthritis, laboratory data were normal. Our data suggest that as in other chronic intestinal diseases, celiac disease in adults, is frequently associated with central joint disease. This high incidence of sacroiliitis, the joint disease most frequently found in our patients, has not been previously reported in other series. We believe, therefore, this difference could be explained by the different methodology used for the screening of joint disease.