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Summary: Sensory processing varies depending on behavioral context. Here, we ask how task engagement modulates neurons in the auditory system. We train mice in a simple tone-detection task and compare their neuronal activity during passive hearing and active listening. Electrophysiological extracellular recordings in the inferior colliculus, medial geniculate body, primary auditory cortex, and anterior auditory field reveal widespread modulations across all regions and cortical layers and in both putative regular- and fast-spiking cortical neurons. Clustering analysis unveils ten distinct modulation patterns that can either enhance or suppress neuronal activity. Task engagement changes the tone-onset response in most neurons. Such modulations first emerge in subcortical areas, ruling out cortical feedback as the only mechanism underlying subcortical modulations. Half the neurons additionally display late modulations associated with licking, arousal, or reward. Our results reveal the presence of functionally distinct subclasses of neurons, differentially sensitive to specific task-related variables but anatomically distributed along the auditory pathway.

Abstract: We examined outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) using T-cell receptor αβ+ (TCRαβ+)/CD19+-depleted grafts (TCR group, 14 patients) in children with hemoglobinopathies. Patients received a preparative regimen consisting of busulfan, thiotepa, cyclophosphamide, and antithymocyte globulin preceded by fludarabine, hydroxyurea, and azathioprine. The median follow-up among surviving patients was 3.9 years. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 84% and 69%, respectively. The incidence of graft failure was 14%. We compared outcomes to a historical group of 40 patients with hemoglobinopathies who received CD34+-selected grafts (CD34 group). The median follow-up of surviving patients for the CD34 group was 7.5 years. The 5-year probabilities of OS and DFS were 78% and 39%, respectively. The CD34 group had a significantly higher incidence of graft failure (45%) than the TCR group (14%) (P = .048). The incidences of grades 2 to 4 acute graft-versus-host disease (GVHD) in the TCR and CD34 groups were 28% and 29%, respectively, and 21% and 10% (P = .1), respectively, for extensive chronic GVHD. Viral reactivation was common in both groups. The overall incidence of posttransplant lymphoproliferative disorders for the entire group was 16%. Among all patients, 5 developed autoimmune hemolytic anemia or thrombocytopenia, with the overall cumulative incidence of 11%. The 2 groups showed suboptimal CD4+ recovery within the first 6 months of transplantation with no significant difference between groups. These data demonstrate that TCRαβ+/CD19+-depleted grafts are associated with a reduced incidence of graft failure, but delayed immune reconstitution and associated morbidity and mortality remain a significant challenge.

Structurally and mechanically similar to the extracellular matrix (ECM), biomimetic hydrogels offer a number of opportunities in medical applications. However, the generation of synthetic microenvironments that simulate the effects of natural tissue niches on cell growth and differentiation requires new methods to control hydrogel feature resolution, biofunctionalization and mechanical properties. Here we show how these goals can be achieved by using a pullulan-based hydrogel, engineered in composition and server as cell-adhesive hydrogel, 3D photo-printable in dimension, ranging from the macro- to the micro-scale dimensions, and of tunable mechanical properties. For this, we used absorbers that limit light penetration, achieving 3D patterning through stereolithography with feature vertical resolution of 200 μm and with overall dimension up to several millimeters. Furthermore, we report the fabrication of 3D pullulan-modified hydrogels by two-photon lithography, with sub-millimetric dimensions and minimum feature sizes down to some microns. These materials open the possibility to produce multiscale printed scaffolds that here we demonstrate to be inert for cell adhesion, but biologically compatible and easily functionalizable with cell adhesive proteins. Under these conditions, successful cell cultures were established in 2D and 3D. Keywords: Hydrogel, Biomaterials, Polysaccharide, Pullulan, 3D printing, Two photon laser lithography, Mesenchymal stromal cells

Background: Local ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards are lacking. This study aimed to assess the impact of LAT on survival of metastatic STS patients and to identify prognostic factors., Methods: In this retrospective multicenter study, 246 STS patients with metastatic disease who underwent LAT on tumor board recommendation between 2017 and 2021 were analyzed. A mixed effects model was applied to evaluate multiple survival events per patient., Results: Median overall survival (OS) after first metastasis was 5.4 years with 1-, 2- and 5-year survival rates of 93.7, 81.7, and 53.1 %, respectively. A treatment-free interval ≥12 months and treatment of liver metastases were positively correlated with progression-free survival (PFS) after LAT (HR = 0.61, p = 0.00032 and HR = 0.52, p = 0.0081, respectively). A treatment-free interval ≥12 months and treatment of metastatic lesions in a single organ site other than lung and liver were positive prognostic factors for OS after first LAT (HR = 0.50, p = 0.028 and HR = 0.40, p = 0.026, respectively) while rare histotypes and LAT other than surgery and radiotherapy were negatively associated with OS after first LAT (HR = 2.56, p = 0.020 and HR = 3.87, p = 0.025). Additional systemic therapy was independently associated with a PFS benefit in patients ≤60 years with ≥4 metastatic lesions (for max. diameter of treated lesions ≤2 cm: HR = 0.32, p = 0.02 and >2 cm: HR = 0.20, p = 0.0011, respectively)., Conclusion: This multicenter study conducted at six German university hospitals underlines the value of LAT in metastatic STS. The exceptionally high survival rates are likely to be associated with patient selection and treatment in specialized sarcoma centers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The development of eco-friendly polymer composites with multifunctional properties aligns with the goals of the circular economy agenda, which aims to minimize waste and promote the sustainable use of resources by closing the loop of product life cycles. Eco-friendly polymer composites play a crucial role in achieving these objectives. The present work focuses on the preparation of fully biobased blends obtained by melt mixing a bio-polyester, poly(butylene succinate-co-adipate) (PBSA), with orange peels up to 20 wt%, to yield active polymer composites. Orange peels, employed here as natural filler, are largely available from food wastes, they are rich in phenolic compounds and possess antioxidant activity as shown by the experimental tests carried out. The thermal stability of the formulated composites is almost unchanged by the filler addition, showing only a slight decrease of the crystallization temperatures and crystalline fraction within the composites. The mechanical properties of the compounds evidence an increase in the elastic modulus together with a decrease in the tensile strength, while the elongation at break remains almost constant. The incorporation of the natural filler enabled the integration of antioxidant and antibacterial properties, which were absent in the original pristine polymer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura Sisti reports financial support was provided by National Recovery and Resilience Plan (NRRP), NextGenerationEU. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Red yeast rice (RYR) is an entirely natural product that originates from the fermentation of white rice (Oryza sativa) with a yeast, mainly Monascus Purpureus, and has been part of traditional Chinese medicine and diet since ancient times. It has generated great interest in recent years in the context of cardiovascular (CV) prevention due to its ability to inhibit endogenous cholesterol production, helping to achieve and maintain optimal plasma lipid concentrations. This review aims to make an extensive 360-degree assessment and summary of the whole currently available scientific evidence about RYR, starting with its biochemical composition, passing through a historical reconstruction of all the studies that have evaluated its efficacy and safety in cholesterol-lowering action, with a focus on CV outcomes, and ultimately addressing its other relevant clinical effects. We also discuss its possible therapeutic role, alone or in combination with other nutraceuticals, in different clinical scenarios, taking into account the positions of major scientific documents on the issue, and describe the articulate legal controversies that have characterized the regulation of its use up to the present day. RYR preparations have been proven safe and effective in improving lipid profile, with a potential role in reducing cardiovascular risk. They can be considered as additional supportive agents in the armamentarium of lipid-modifying therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fungicides, insecticides and herbicides are widely used in agriculture to counteract pathogens and pests. Several of these molecules are toxic to non-target organisms such as pollinators and their lethal dose can be lowered if applied as a mixture. They can cause large and unpredictable problems, spanning from behavioural changes to alterations in the gut. The present work aimed at understanding the synergistic effects on honeybees of a combined in-hive exposure to sub-lethal doses of the insecticide thiacloprid and the fungicide penconazole. A multidisciplinary approach was used: honeybee mortality upon exposure was initially tested in cage, and the colonies development monitored. Morphological and ultrastructural analyses via light and transmission electron microscopy were carried out on the gut of larvae and forager honeybees. Moreover, the main pollen foraging sources and the fungal gut microbiota were studied using Next Generation Sequencing; the gut core bacterial taxa were quantified via qPCR. The mortality test showed a negative effect on honeybee survival when exposed to agrochemicals and their mixture in cage but not confirmed at colony level. Microscopy analyses on the gut epithelium indicated no appreciable morphological changes in larvae, newly emerged and forager honeybees exposed in field to the agrochemicals. Nevertheless, the gut microbial profile showed a reduction of Bombilactobacillus and an increase of Lactobacillus and total fungi upon mixture application. Finally, we highlighted for the first time a significant honeybee diet change after pesticide exposure: penconazole, alone or in mixture, significantly altered the pollen foraging preference, with honeybees preferring Hedera pollen. Overall, our in-hive results showed no severe effects upon administration of sublethal doses of thiacloprid and penconazole but indicate a change in honeybees foraging preference. A possible explanation can be that the different nutritional profile of the pollen may offer better recovery chances to honeybees., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Food waste valorization, considered as energy and/or chemicals source, via biorefinery or biotechnology, gained great attention in recent years, because of the fast depletion of primary resources, increased waste generation and landfilling worldwide. Coffee by-products for example (i.e. coffee pulp, coffee husks, silver skin, spent coffee, etc.) have been investigated in different forms either as a source of antioxidant and valuable chemicals and as a filler in composites. A new valorization route for coffee silver skin (CSS), up to now just sent to damping, is here investigated: particulate bio-composites based on poly(butylene succinate-co-adipate) (PBSA), an aliphatic biodegradable polyester commercially available, have been formulated with up to a 30 wt% of CSS, in order to prepare mulching films for agriculture. The bacterial analysis of the filler indeed, has underlined the presence of potential Plant Growth-Promoting Bacteria species, mainly ascribed to the Bacillus genus, which can survive both the roasting and the compounding processes. The obtained composites have been characterized mechanically and thermally and their hydrophilic nature has been investigated by measuring their contact angle. Eventually, the bacteria release from the composite films has been examined by means of in-vitro tests. The plant growth promoting capability of the films was preliminarily evaluated in pot experiments using lettuce as a model crop. The composite films were able to release the endogenous bacteria in the soil and to stimulate plant and root growth of the assayed crop. The possibility to produce functionalized biodegradable mulching films by recycling agricultural wastes can thus be forecast, highlighting potential multiple advantages in terms of soil preservation/fertilization, decrease of polymeric materials in mulching products, exploitation of a waste., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bees can be severely affected by various plant protection products (PPP). Among these, neonicotinoid insecticides are of concern as they have been shown to be responsible for extensive honeybee colonies death when released into the environment. Also, sublethal neonicotinoid doses contaminating single honeybees and their colonies (e.g. through contaminated pollen) are responsible for honeybees physiological alterations with probable implication also on microbiome functionality. Honeybees show symbiotic interactions with specific gut bacteria that can enhance the adult host performances. Among the known mechanisms, the modulation of the immune system, the degradation of recalcitrant secondary plant metabolites, pollen digestion, and hormonal signaling, are the most important functional benefits for the host honeybee. To date, few research efforts have aimed at revealing the impact of PPP on the gut microbial community of managed and wild honeybees. The majority of the existing literature relays on cage or semifield tests of short duration for research investigating neonicotinoids-gut microbiome interactions. This research wanted to unravel the impact of two neonicotinoids (i.e. imidacloprid and thiacloprid) in natural field conditions up to 5 weeks of exposure. A long-term impact of neonicotinoids on gut microbial community of honeybees was observed. The alterations affected several microbial genera and species such as Frischella spp., lactobacilli and bifidobacteria, whose shifting is implicated in intestinal dysbiosis. Long-term impact leading to dysbiosis was detected in case of exposure to imidacloprid, whereas thiacloprid exposure stimulated temporary dysbiosis. Moreover, the microbial diversity was significantly reduced in neonicotinoid-treated groups. Overall, the reported results support a compromised functionality of the gut microbial community, that might reflect a lower efficiency in the ecosystemic functionality of honeybees., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background & Aims: Celiac disease (CD) is an immune-mediated systemic disease, caused by ingestion of gluten in genetically predisposed individuals. Gut microbiota dysbiosis might play a significant role in pathogenesis of chronic enteropathies and its modulation can be used as an intervention strategy in CD as well. In this study, we aimed to identify correlations between fecal microbiota, serum tumor necrosis factor alpha (TNF-α) and fecal short-chain fatty acids (SCFAs) in healthy children and children with CD after administration of probiotic Bifidobacterium breve BR03 and B632., Methods: A double-blind placebo-controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC). CD children were randomly allocated into two groups, of which 20 belonged to the placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a probiotic formulation containing a mixture of 2 strains, B. breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for statistical analysis, blood and fecal samples from CD children (on enrolment - T0 and after 3 months, at the end of intervention with probiotic/placebo - T1) and HC children were used. The HC group was sampled only once (T0)., Results: Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea may be involved in the disease, indicated by a strong correlation to TNF-α. Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The effect of probiotic administration has disclosed a negative correlation between Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and some SCFAs, turning them into an important target in microbiome restoration process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory process in healthy human gut., Conclusions: Our results highlight new phyla, which may have an important relation to disease-related parameters, CD itself and health., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Kinetics of CA 15-3 and CEA have a high specificity in the early detection of metastatic breast cancer (MBC). However, this high specificity is associated with a lack of sensitivity. To decrease the number of false negative patients, the additional diagnostic potential of an extended panel of biomarkers was evaluated., Methods: This analysis was performed as part of a large follow-up study (1998-2010) evaluating 813 patients with a median follow-up of 63months. After primary therapy, all patients underwent tumor marker monitoring for CEA and CA 15-3 at 6-week intervals. A reproducible previously defined increase (≥100%) based on the individual baseline value of each patient was considered as a strong indicator of MBC. For the present analysis, we retrospectively evaluated 1011 blood samples from 95 patients. Forty-seven of these had metastatic disease for the first time at the time of this evaluation, while the remaining 48 patients showed no evidence of disease. The sera of these patients were additionally assessed for the following parameters: cancer antigen (CA) 125, cytokeratin-19 soluble fragment (CYFRA 21-1), HER2 shed antigen, lactate-dehydrogenase (LDH) and C-reactive protein (CRP)., Results: 26 of 47 patients with MBC showed a reproducible tumor marker increase of at least CEA and/or CA 15-3 (55.3%, true-positive). The remaining 21 patients with MBC showed no increase in CEA or CA 15-3 (44.7%, false negative, FN). By combining all markers mentioned above, 41 of 47 patients with MBC showed a reproducible marker increase with a sensitivity of 87.2% and specificity of 100%., Conclusion: This retrospective analysis indicates that a panel of biomarkers can increase the sensitivity of the CA 15-3/CEA combination without loss of specificity. The combined use is therefore helpful for early detection of MBC., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: We investigated the diagnostic capacity of CEA and CA 15-3 kinetics for the early detection of metastatic disease in comparison to fixed cut off values., Methods: In a retrospective analysis, a total of 743 patients with early breast cancer and available baseline values of CEA and CA 15-3 were included. A reproducible increase of 100% of single or combined markers was considered as a strong indicator of metastatic disease., Results: 187 patients developed metastatic disease and 556 remained disease-free. On the basis of tumor marker kinetics, we reached a specificity of >98% for both biomarkers and a sensitivity of 40.6% for CEA alone, 55.6% for CA 15-3 alone and 66.3% for the combination of both markers. Using fixed cut-off values (CEA: 4ng/mL, CA 15-3: 30U/mL) we ended up with a specificity of 86.3% and a sensitivity of 70.6% for the combination of CEA and CA 15-3. Using higher cut-off values (CEA: 6ng/mL, CA 15-3: 60U/mL) we reached a specificity of 96.9% and a sensitivity of 49.7% for the combination., Conclusion: We conclude that the interpretation of these markers in follow-up using individual baseline values and kinetics leads to a significant superior profile of specificity and sensitivity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aim: HER2 in breast cancer tissue is a marker of high prognostic and predictive relevance. Soluble HER2, the extracellular domain of the HER2/neu receptor (HER2 ECD), which is shed into the blood, has been suggested to be a helpful tumor marker. We investigated the relationship between the concentrations of HER2 ECD, CEA and CA 15-3, the association of these markers with clinicopathological features and the impact of HER2 ECD alone and in combination with known prognostic factors on disease free survival (DFS) and cancer specific survival (CSS) in untreated early breast cancer patients., Patients and Methods: HER2 ECD (ADVIA, Bayer), CEA (AxSYM, Abbott) and CA 15-3 (Elecsys, Roche) were measured at time of primary diagnosis in the pre-therapeutic (pre-operative) sera of 241 breast cancer patients and were correlated with clinicopathological parameters and outcome., Results: Higher HER2 ECD levels were significantly correlated with postmenopausal status (p=0.016) and tissue HER2-overexpression (p<0.0001). Higher serum levels of CA 15-3 were associated with larger tumor size (p=0.019), positive lymph nodes (p=0.019), UICC stage III (p<0.01), positive tissue HER2-overexpression (p<0.05) and negative hormone receptor status (p=0.016). In multivariate analysis, serum HER2 ECD levels, CA 15-3 levels, large tumor size and negative hormonal status were independent prognostic factors in DFS. Patients with both high levels of HER2 ECD (>15 ng/mL) and high serum levels of CA 15-3 (>24 U/mL) had the poorest prognosis with a DFS after 3 years of 50.0%. Patients without elevated serum levels had a better outcome with a DFS of 91.2%., Conclusions: In our retrospective analysis, HER2 ECD and CA 15-3 were independent and better prognostic tools than HER2 in tissue. Prospective validation is necessary to confirm their usefulness in clinical practice., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The extensive use of silver nanoparticles (SNPs) as antimicrobial in food, clothing and medicine, leads inevitably to a loss of such nanomaterial in soil and water. Little is known about the effects of soil contamination, in particular, on microbial cells, which play a fundamental ecological role. In this work, the impact of SNPs on forest soil has been studied, investigating eco-physiological indicators of microbial biomass and microbial diversity with culture-dependent and independent techniques. Moreover, SNPs bioavailability and uptake were assessed. Soil samples were spiked with SNPs at two different concentrations (10 and 100 μg g(-1)dw) and incubated with the relative controls for 30, 60 and 90 days. The overall parameters showed a significant influence of the SNPs on the soil microbial community, revealing a marked shift after 60 days of incubation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Anti-Listeria bacterial starters are highly demanded by the meat industry. Novel bioprotective anti-Listeria starters were searched among Lactobacillus species strains isolated from artisanal sausages. The screening confirmed that anti-Listeria activity is a strain-specific property and yielded only 1 strain (of 36) exhibiting a satisfactory level of inhibition, L. delbrueckii WC0286. This strain was compared with two commercial bioprotective starters, SafePro B-SF-43 and SafePro B-LC-20, in a model simulating in vitro the first step of the fermentation process. The presence of the bioprotective starters did not modify the pH in such a way that could affect the safety or organoleptic properties of the product. Both SafePro B-SF-43 and SafePro B-LC-20 effected an important reduction of Listeria counts (0.56 and 0.72 log CFU g(-1), respectively, in 72 h), while the anti-Listeria effect of L. delbrueckii WC0286 was minor (0.15 log CFU g(-1)). These results discouraged the utilization of L. delbrueckii WC0286 for a challenge test in a pilot salami production, in favor of the best-performing bioprotective starter, SafePro B-LC-20. The test confirmed that SafePro B-LC-20 did not alter the acidification trend of sausages and was capable of inhibiting Listeria, which decreased by 1.21 log CFU g(-1). This information is relevant to address research activity toward the development of new bioprotective starters. The data herein presented demonstrate that the efficacy in Listeria control of potentially bioprotective bacterial starters requires further validation in real meat matrixes, possibly by using in vitro meat fermentation experiments to narrow down the list of candidates before pilot scale challenge tests.

Aim: HER2 in tissue is of high prognostic value. Soluble HER2, the extracellular domain (ECD), has been suggested to be a helpful biomarker. We investigated whether there is a relationship between HER2 ECD and HER2 in tissue and whether this relationship could be used for diagnostic purposes., Methods: HER2 ECD was measured in healthy individuals (N=283, 184 females, 99 males), in patients with history of breast cancer (BC) with no evidence of disease (N=249) as well as in BC patients before any treatment (N=565). HER2 in tissue was determined by immunohistochemistry and HER2 ECD was analyzed by immunoassay., Results: HER2 ECD levels were higher in healthy men than in healthy women (medians 12.9 ng/mL vs. 9.9 ng/mL, p<0.001). We observed an age dependency in women that means the older the women the higher the HER2 ECD level. In treated BC patients there was only a weak difference between younger and older women. For patients without distant metastases as well as patients with metastatic disease we observed a correlation of HER2 in serum and tissue. The median concentrations of HER2 ECD were 11.7 ng/mL (13.2 ng/mL) for the HER2-negative (HER2-positive) patients in the non-metastatic-group (p<0.001) and 11.9 ng/mL (16.0 ng/mL) in the metastatic-group (p=0.01). Using a cut-off of 30 ng/mL the HER2 in tissue was always positive, corresponding to a specificity of 99.8% and a sensitivity of 10.3%., Conclusions: There is a strong correlation between HER2 ECD and HER2 in tissue. HER2 ECD supports the HER2 testing in tissue and may reveal false-negative tissue findings., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Turfgrasses are not only designed for recreation activities, but they also provide beneficial environmental effects and positively influence the human wellness. Their major problems are predisposition to tearing out and microbial diseases. The aim of this study was to investigate whether the inoculation of microorganisms can be effective to improve plant growth and root development of perennial ryegrass, to evaluate new sustainable practice for green preservation. A microorganism-based commercial product was used to amend hydroponically grown Lolium perenne L. and results compared with the use of the same filtered product, a phytohormone solution and an untreated control. Plants were grown for five weeks, shoots cut and measured at one-week interval and, at the end, roots were measured for length and weight. Shoot resistance to tearing out was also tested. Moreover, the main microbial groups present in the product were characterized and the microbial profile of sand and root samples was investigated by PCR-DGGE. The plants treated with the product showed an increased resistance to tearing out with respect to other treatments and roots were longer with respect to the control. Microbial analyses of the product evidenced bacterial and yeast species with plant growth promoting activity, such as Stenothrophomonas maltophilia, Candida utilis and several Lactobacillus species. Some Lactobacillus strains were also found to be able to colonize plant roots. In conclusion, the treatment with microorganisms has a great potential for the maintenance and increased performance of turfgrass surfaces., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer., Patients and Methods: Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m(2) on day 1 followed by oral vinorelbine at a dose of 60 mg/m(2) on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals., Results: Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance., Conclusion: The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks.

Nonylphenol ethoxylates (NPnEOs, where n is the number of ethoxylic units in the molecule) are non-ionic surfactants widely used for domestic and industrial purposes. 4-Nonylphenol (4-NP), the main product of NPnEO biodegradation, is a toxic xenobiotic compound classified as endocrine disrupter. While numerous studies reported the toxicity and oestrogenic activity of nonylphenols, little is known about the mutagenicity of these compounds. In this paper, the genotoxicity of 4-NP and NPnEO mixtures was evaluated by using the D7 strain of Saccharomyces cerevisiae as experimental model. The same genotoxicity tests were applied to effluents deriving from experimental packed-bed bioreactors, developed for the treatment of NPnEO contaminated wastewater, in order to evaluate the residual genotoxic potential with respect to the influent waste. The target compounds fed to the bioreactors were 4-NP and NPnEO mixtures possessing an average of 5 or 1.5 ethoxylic units (Igepal CO-520 and Igepal CO-210, respectively). The results showed that 4-NP induced significant cytotoxic effect on S. cerevisiae cells at 50 mg/L, as well as mutagenic effects at the lowest tested concentrations (12 and 25 mg/L). 4-NP was the most genotoxic compound among those assayed, followed by Igepal CO-210, whereas Igepal CO-520 did not induce genotoxicity at any of the assayed concentrations. The genotoxic effects of 4-NP on yeast cells disappeared after the treatment of 4-NP artificially contaminated water in the bioreactor. This indicates that the biological treatment is capable of removing not only the pollutant, but also the toxicity associated to the compound and its degradation metabolites. This study represents, to the best of our knowledge, the first report that evaluates the genotoxicity of both 4-NP, NPnEOs and their potential aerobic degradation products on an eukaryotic organism. The obtained results suggest that the S. cerevisiae D7 strain is a very effective model microorganism to study the induction of genotoxic damage by the compounds under study. Moreover, this yeast assay has been proved effective to evaluate the detoxification effect deriving from biotreatment processes., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Three bacterial strains were isolated from activated sludge samples of two treatment plants receiving domestic and industrial wastewaters containing polyethoxylated nonylphenols. One strain (VA160) was isolated on rich medium, and the other two (BCaL1 and BCaL2) on mineral medium containing two industrial mixtures of nonylphenol ethoxylates as the sole carbon source. Strain VA160 was a Gram-positive, spore forming, filamentous bacterium, producing aggregates during growth in liquid medium. On the basis of phylogenetic analysis the strains were assigned to the Bacillus (VA160), Acinetobacter (BCaL1) and Stenothrophomonas (BCaL2) genera. High performance liquid chromatography analysis showed that only the Acinetobacter and Stenothrophomonas strains were involved in the degradation of polyethoxylated nonylphenols. Bacillus VA160, however, when co-cultured with the two degrading strains, induced the formation of cell aggregates and facilitated NPEO degradation. Fluorescent in situ hybridisation on the activated sludge sample from which Bacillus VA160 was isolated, using probes for Gram-positive bacteria with low G + C content, showed that bacteria belonging to this group specifically occurred inside the examined flocs. These observations suggest that the enhanced biodegradation of polyethoxylated nonylphenols in the three-membered co-culture is favoured by VA160-induced aggregation of BcaL1 and BcaL2 cells involved in the process.

A large human nonimmune phage antibody library was screened by affinity chromatography to select single-chain antibodies directed against the human receptor tyrosine kinase (RTK) Ron. As antigen, we used a GST fusion protein (GST-IRP(-)) containing the whole intracellular portion of Ron except for the carboxyl-terminal arginine-proline-rich motif. One selected phage was highly specific for Ron when tested in an enzyme-linked immunosorbent assay (ELISA). We report here the immunological characterization of this anti-Ron single-chain antibody (sc7) and show that it recognizes both denatured and native forms of the receptor. The epitope bound by sc7 maps within the first 50 amino acid residues of the juxtamembrane domain of Ron. This monoclonal fragment does not cross-react with other receptor tyrosine kinases including the closely related human proto-oncogene Met. We demonstrate that the isolated antibody fragment interacts in vivo with the intracellular domain of Ron in mammalian cells.

Two aerobic bacterial strains, a chlorophenol-degrading bacterium characterized in this work as a Ralstonia sp. LD35 on the basis of the sequence of the gene encoding for 16S ribosomal RNA, and Pseudomonas putida DSM 1868, capable of metabolizing 4-methoxybenzoic acid, were tested for their capacity to degrade monocyclic aromatic acids responsible for the toxicity of olive mill wastewaters (OMWs). Both strains possess interesting and complementary degradation capabilities in resting cell conditions: Ralstonia sp. LD35 was found to metabolize 4-hydroxybenzoic, 4-hydroxyphenylacetic, 3,4-dihydroxycinnamic and cinnamic acid, whereas DSM 1868 was capable of metabolizing 4-hydroxy-3-methoxybenzoic, 3,4-dimethoxybenzoic and 4-hydroxy-3,5-dimethoxybenzoic acid, as well as 4-hydroxybenzoic and 4-hydroxyphenylacetic acid. The kinetic parameters describing the growth of the two strains on the same compounds were determined in growing-cell batch conditions, and showed that both strains presented high affinity and high specific growth rates towards all assayed substrates. In addition, the two strains were capable of growing on and extensively biodegrading a mixture of monocyclic aromatic acids commonly found at high concentrations in OMWs, and of growing on a 20% dilution of a natural OMW. All these features make the two strains attractive candidates for the development of a biotechnological process for the biodegradation of aromatic compounds found in OMWs.

Objective: The prognostic value of the nucleated red blood cell count at birth with respect to perinatal brain damage and neonatal outcome was assessed in infants at high risk of having neurologic damage., Study Design: The nucleated red blood cell count at birth, pulsed Doppler ultrasonography in the cerebral arteries, cranial fontanelle sonograms, and neurodevelopmental status were evaluated in 337 newborn infants., Results: The nucleated red blood cell count at birth was significantly higher (1) in neonates with abnormal Doppler ultrasonographic parameters for the cerebral arteries at 48 to 72 hours after birth than in healthy neonates, (2) in 6-month-old infants with sequelae of hypoxic-ischemic encephalopathy than in healthy infants, and (3) in 3-year-old children with abnormal developmental status than in those with no abnormalities at follow-up. Significant correlations were observed between the nucleated red blood cell count and gestational age, Apgar score at 1 and 5 minutes, pH, base deficit, fraction of inspired oxygen, blood oxygen content, and birth weight., Conclusions: The nucleated red blood cell count at birth not only reflects a response of the infant to perinatal hypoxia but is also a reliable index of perinatal brain damage.

Pyrocatechase activity was studied in the Pseudomonas sp. CPE2 strain, which is capable of growing on 2-chlorobenzoic and 2,5-dichlorobenzoic acid, giving rise to catechol and 4-chlorocatechol, respectively, as intermediate metabolites. The CPE2 crude extract was found to metabolize both catechol and 4-chlorocatechol. Enzymatic as well as phenotypic studies performed both on this strain and on a mutant strain lacking the chlorocatechol-degrading genes were consistent with the presence of two catechol-cleaving enzymes, one active mainly against catechol (pyrocatechase I) and the other with broader substrate specificity (pyrocatechase II). The latter enzyme also appeared to be induced when CPE2 cells were grown on 2-chlorobenzoic acid, thus contributing to catechol metabolism, in addition to pyrocatechase I. Despite the presence of a large plasmid in CPE2 cells, the chlorocatechol-degrading genes, highly homologous to the clc operon, were located on the chromosome. The selection at relatively high frequency of mutant strains with altered growth capabilities and which lacked the chlorocatechol-degrading genes suggests a transposon-like character for these catabolic genes in the CPE2 strain.

Nineteen healthy young women, non-smokers and of normal weight, used a combined oral contraceptive, consisting of 20 micrograms ethinylestradiol and 150 micrograms desogestrel, for 9 cycles and were investigated before starting oral contraceptive use, and during the 3rd, 6th and 9th cycle. In all cases, the antioxidant erythrocyte enzyme activities, superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px), were determined. Pyruvate-kinase (PK) activity was also considered as a predictable index of the age and constancy of the erythrocyte population. A steady, significant increase in GSH-Px and CAT enzyme activities was found. No significant variations were found in SOD and PK enzyme levels. These findings clearly suggest that the use of combined oral contraceptives leads to an increase in antioxidant defenses. The specific physiological and biochemical mechanisms of this response merit further investigation.