Different Strategies to Obtain Corn (Zea mays L.) Germ Extracts with Enhanced Antioxidant Properties

Maize ( Zea mays L.) germs are by-products from the milling industry. The objective of this work was to compare the phenolic and lipophilic antioxidant fractions of yellow and white corn varieties, provided by Corn Valley S.r.l. (Piumbega, Mantova, Italy) and among the raw materials most processed by the company. The phenolic fraction, extracted with ultrasound-assisted extraction, alone and in combination with chemical and enzymatic hydrolyses, was analyzed with high-performance thin-layer chromatography and reversed-phase high-performance liquid chromatography-diode array detector. Among the various extraction techniques used, the combination of sonication and alkaline hydrolysis proved to be an effective method for the extraction of phenolic compounds from yellow and white germs, with the highest ferulic acid concentrations (636.54 ± 3.71 and 569.23 ± 1.69 mg FA/g dried extract, respectively), total phenolic contents (844.5 ± 64.6 and 742.8 ± 15.44 mg gallic acid equivalents/g dried extract, respectively), and the best antioxidant activity (14.33 ± 0.48 and 11.41 ± 1.1 µg/mL, respectively). The lipophilic fraction, extracted using supercritical carbon dioxide was analyzed by gas chromatography-mass spectrometry. The unsaponifiable fractions were found to be 2.41% ± 0.24% in yellow corn and 1.85% ± 0.08% in white corn; β-sitosterol, campesterol, and stigmasterol were identified as the main phytosterols characterizing both lipophilic extracts which showed the most effective antioxidant activity (1.29 ± 0.26 mg/mL and 1.33 ± 0.21 mg/mL, respectively) compared with the control. Finally, the phenolic and lipophilic extracts obtained from maize by-products may be reintroduced into the health-oriented market as extracts enriched of high-added value biomolecules with antioxidant activity both as active molecules and as additives of natural origin

The state of the art of the management of anticoagulated patients with mild traumatic brain injury in the Emergency Department

The effects of Oral Anticoagulation Therapy (OAT) in older patients who suffered a mild Traumatic Brain Injury (mTBI) are widely debated but still strong guidelines are lacking and clinical approaches and management are sometimes heterogeneous. Different predictors of adverse outcomes were identified in the literature but their use in the decision-making process is unclear. Moreover, there is no consensus on the appropriate length of stay in the Observation Unit nor on the continuation of OAT, even if the diagnosis of life-threatening delayed post-traumatic Intracranial Hemorrhage is rare. The recurrence of a control CT scan is often needless. This review aims to summarize recent scientific literature focusing on patients with mTBI taking OAT and to identify crucial questions on the topic to suggest a best clinical practice

polyphenols from vitis vinifera lambrusco by products leaves from pruning extraction parameters evaluation through design of experiment

Vitis vinifera L. leaves from pruning are by-products of the wine industry and represent an important source of secondary raw material, thanks to their polyphenols content. Optimization of the extraction processes is a key factor for their valorization, and Design of Experiment (DOE) could be a tool to obtain the most performing extract in terms of polyphenols quality/quantity and bioactivity. Vitis vinifera Lambrusco leaves were subjected to ultrasound-assisted extractions guided by a 23 factorial design. Three independent parameters (% solvent, time of extraction, and solvent:solid ratio) were considered to evaluate the extraction process by analyzing the extraction yield, the total phenolic content (Folin-Ciocalteu assay), and the antioxidant capacity (DPPH assay). Moreover, the content of the main molecules was identified and quantified by reversed-phase high-performance liquid chromatography coupled with diode array detection and mass spectrometry. The DOE highlighted the best extraction conditions that showed slight changes considering the different evaluating parameters. The highest extraction yield was obtained by extraction with 100% water, 60 minutes of extraction time, and 30:1 solvent:solid ratio, but it was neither the richest in polyphenols nor antioxidant capacity. The latter 2 characteristics were associated with the extraction performed using 50% ethanol, 35 minutes of extraction time, and a 20:1 solvent:solid ratio. That extract also exhibited the highest quantity of flavonols

Bubble technique for Descemet membrane endothelial keratoplasty tissue preparation in an eye bank: Air or liquid?

Purpose To compare the big-bubble method using air and liquid as medium of separation for Descemet membrane endothelial keratoplasty (DMEK) lenticule preparation in an eye bank. Methods Donor corneas (n = 20) were immersed in liquid [tissue culture medium (TCM)]. Air and liquid was injected using a 25-gauge needle in the posterior stroma or as near to the stroma-Descemet membrane (DM) phase as possible to create a complete bubble of larger diameter. The endothelial cell density and mortality were checked pre- and postbubble after deflating the tissue. Four pairs of tissues were used to analyse the intracellular tight junctions and three pairs for histological examination and DNA integrity studies, respectively. Results The yield obtained using air was 80%, whereas that with liquid was 100%. Single injection was required in six cases; twice in two cases; three and four times in one case each with air bubble, whereas seven cases required single injection; twice in two cases; and thrice in just one case with liquid bubble. The average diameter of the final lenticule was 9.12 (± 1.71) mm for air bubble and 9.78 (± 1.75) mm for liquid bubble with p = 0.4362 (no statistical significance). Endothelial cell mortality postbubble preparation was 8.9 (± 12.38) % for air and 6.25 (± 9.57) % for liquid (p = 0.6268). Conclusions DM and endothelium could be separated exclusively using air or liquid bubble. However, liquid bubble seems to have certain advantages over air such as the generation of yield, larger diameter and higher maintenance of endothelial cell density and integrity

Epithelial thymic tumours in paediatric age: a report from the TREP project

<p>Abstract</p> <p>Background</p> <p>Thymic epithelial tumours (thymoma and carcinoma) are exceptionally rare in children. We describe a national multicentre series with a view to illustrating their clinical behaviour and the results of treatment.</p> <p>Methods</p> <p>From January 2000 all patients under 18 years of age diagnosed with "<it>rare paediatric tumours</it>" were centrally registered by the Italian centres participating in the TREP project (<b>T</b>umori <b>R</b>ari in <b>E</b>tà <b>P</b>ediatrica [Rare Tumours in Paediatric Age]). The clinical data of children with a thymic epithelial tumour registered as at December 2009 were analyzed for the purposes of the present study.</p> <p>Results</p> <p>Our series comprised 4 patients with thymoma and 5 with carcinoma (4 males, 5 females; median age 12.4 years). The tumour masses were mainly large, exceeding 5 cm in largest diameter. Based on the Masaoka staging system, 3 patients were stage I, 1 was stage III, 1 was stage IVa and 4 were stage IVb.</p> <p>All 3 patients with stage I thymoma underwent complete tumour resection at diagnosis and were alive 22, 35 and 93 months after surgery. One patient with a thymoma metastasizing to the kidneys died rapidly due to respiratory failure.</p> <p>Thymic carcinomas were much more aggressive, infiltrating nearby organs (in 4 cases) and regional nodes (in 5), and spreading to the bone (in 3) and liver (in 1). All patients received multidrug chemotherapy (platinum derivatives + etoposide or other drugs) with evidence of tumour reduction in 3 cases. Two patients underwent partial tumour resection (after chemo-radiotherapy in one case) and 4 patients were given radiotherapy (45-54 Gy). All patients died of their disease.</p> <p>Conclusions</p> <p>Children with thymomas completely resected at diagnosis have an excellent prognosis while thymic carcinomas behave aggressively and carry a poor prognosis despite multimodal treatment.</p

Dissecting the effect of soil on plant phenology and berry transcriptional plasticity in two Italian grapevine varieties (Vitis vinifera L.)

Grapevine embodies a fascinating species as regards phenotypic plasticity and genotype-per-environment interactions. The terroir, namely the set of agri-environmental factors to which a variety is subjected, can influence the phenotype at the physiological, molecular, and biochemical level, representing an important phenomenon connected to the typicality of productions. We investigated the determinants of plasticity by conducting a field-experiment where all terroir variables, except soil, were kept as constant as possible. We isolated the effect of soils collected from different areas, on phenology, physiology, and transcriptional responses of skin and flesh of a red and a white variety of great economic value: Corvina and Glera. Molecular results, together with physio-phenological parameters, suggest a specific effect of soil on grapevine plastic response, highlighting a higher transcriptional plasticity of Glera in respect to Corvina and a marked response of skin compared to flesh. Using a novel statistical approach, we identified clusters of plastic genes subjected to the specific influence of soil. These findings could represent an issue of applicative value, posing the basis for targeted agricultural practices to enhance the desired characteristics for any soil/cultivar combination, to improve vineyards management for a better resource usage and to valorize vineyards uniqueness maximizing the terroir-effect

Artificial Antigen Presenting Cells With Preclustered anti-CD28/-CD3/-LFA-1 Monoclonal Antibodies Are Highly Effective To Induce The Ex-Vivo Expansion Of Functional Human Antitumor T Cells

Effective adoptive T cell therapy requires the _ex vivo_ generation of functional T lymphocytes with a long lifespan _in vivo_. We evaluated _in vitro_ T cell expansion by artificial antigen presenting cells (aAPC) generated with activating (human anti-CD3), co-stimulating (human anti-CD28) and adhesion (human anti-LFA-1) monoclonal antibodies pre-clustered in microdomains (MDs) held by a liposome scaffold. The co-localization of T cell ligands in MDs and the targeting of an adhesion protein, increasing the efficiency of immunological synapse formations, represent the novelties of our system. These aAPCs allowed increased expansion of polyclonal CD4^+^ and CD8^+^ T cells and of tumor antigen-specific CD8^+^ T cells compared to anti-CD28- and anti-CD3-coated microbeads and to immobilized anti-CD3. These aAPCs allowed the generation of T cells displaying an immunophenotype consistent with long-term _in vivo_ persistence, without increasing the frequency of regulatory T cells. Finally, our aAPCs proved to be suitable for large scale T cell expansion required in immunotherapy trials

An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (Ctl)-Defined, Melanocyte-Specific Antigen in Metastatic Melanoma Patients Impacts on Generation of Peptide-Specific Ctls but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions

It is not known if immune response to T cell–defined human histocompatibility leukocyte antigen (HLA) class I–restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA–peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-127–35–specific CTL precursors (CTLp) were ≥1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO+ memory T cell subset. In the remaining five patients, a low (<1/40,000) peptide-specific CTLp frequency was measured, and the precursors were only in the CD45RA+ naive T cell subset. Evaluation of CTL effector frequency after bulk culture indicated that peptide-specific CTLs could be activated in all patients by using professional antigen-presenting cells as dendritic cells, but CTLp frequency determined the kinetics of generation of specificity and the final number of effectors as evaluated by both limiting dilution analysis and staining with HLA-A*0201–Melan-A/Mart-1 tetrameric complexes. Immunohistochemical analysis of 26 neoplastic lesions from the nine patients indicated absence of tumor regression in most instances, even in patients with an expanded peripheral T cell pool to Melan-A/Mart-1 and whose neoplastic lesions contained a high frequency of tetramer-positive Melan-A/Mart-1–specific T cells. Furthermore, frequent lack of a “brisk” or “nonbrisk” CD3+CD8+ T cell infiltrate or reduced/absent Melan-A/Mart-1 expression in several lesions and lack of HLA class I antigens were found in some instances. Thus, expansion of peripheral immune repertoire to Melan-A/Mart-1 takes place in some metastatic patients and leads to enhanced CTL induction after antigen-presenting cell–mediated selection, but, in most metastatic lesions, it does not overcome tumor escape from immune surveillance

Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: A systematic review and meta-analysis of randomized clinical trials

Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto\ue2\u80\u99s method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up