LOKIBASE is a non-linear isolator/dissipator device to protect pallet racking systems against the earthquake.LOKIBASE consists of the following main components:(1)two slider devices on which a rubber membrane is set u...LOKIBASE is a non-linear isolator/dissipator device to protect pallet racking systems against the earthquake.LOKIBASE consists of the following main components:(1)two slider devices on which a rubber membrane is set up(LOKI devices).LOKI devices are linear displacement dependent ones;(2)a cylindrical beam damper(“CANDLE”device).The“CANDLE”device is a non-linear displacement dependent one;(3)two anti-lifting devices(“UP-LIFT”devices);(4)a fuse plug(see www.lokibasedevice.com).The main work which is the purpose of the paper,is the optimization of the behavior of an isolator/dissipator device to mitigate the seismic action on special structures,where the stiffness values are very different in the main cross-aisle and down-aisle directions.Under seismic action,in these structures it is very important to reduce the value of the forces at the Limit state for the safeguard of human life(SLV)in the down-aisle direction as much as possible and simultaneously to use the highest damping value allowed by the building rules to reduce the LOKIBASE displacement at the Limit state for collapse prevention(SLC)in the cross-aisle direction.The goal was achieved through a cylindrical device made of stainless steel(AISI304)with an optimized shape,under large displacement during seismic action.展开更多
BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury...BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.展开更多
Background:Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction.This was a sensitivity analysis of a drug(...Background:Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction.This was a sensitivity analysis of a drug(tetracosactide;TCS10)targeting melanocortin receptors(MCRs)in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.Methods:Sensitivity analysis was based on a randomized,two-arm,multicenter,double-blind,controlled trial.The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs outputs in 100 consecutive cases(from August to September 2013 from Emilia Romagna region,Italy).Patients included an agent-based TCS10 group(10 mg,single intravenous bolus before surgery;n=56)and control group(n=44)and the association with cytokines,lactate,and bleeding-blood transfusion episodes with the prior-risk log odds for mortality rate in time-to-event was analyzed.Results:Thirty-day mortality was significantly improved in the TCS10 group vs.control group(0 vs.8 deaths,P<0.0001).Baseline levels of interleukin(IL)-6,IL-10,and lactate were associated with bleeding episodes,independent of TCS10 treatment[odds ratio(OR)=1.90,95%confidence interval(CI)1.39-2.79;OR=1.53,95%CI 1.17-2.12;and OR=2.92,95%CI 1.40-6.66,respectively],while baseline level of Fms-like tyrosine kinase 3 ligand(Flt3L)was associated with lower bleeding rates in TCS10-treated patients(OR=0.31,95%CI 0.11-0.90,P=0.03).For every 8 TCS10-treated patients,1 bleeding case was avoided.Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group(OR=0.32,95%CI 0.14-0.73,P=0.01).For every 4 TCS10-treated patients,1 transfusion case was avoided.Conclusions:Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care.To introduce the technology readiness level in real-life critically ill patients,further large-scale studies are required.Trial registration:European Union Drug Regulating Authorities Clinical Trials Database(EudraCT Number:2007-006445-41).展开更多
Saponins can be potential candidates for the development of safe biopesticides,due to their widely acknowledged insecticidal,fungicidal and nematicidal activity,but information on their effects on soil biological prop...Saponins can be potential candidates for the development of safe biopesticides,due to their widely acknowledged insecticidal,fungicidal and nematicidal activity,but information on their effects on soil biological properties is still limited.This study aimed to investigate the short-term fate of saponins from Medicago sativa in soil and their dose-effect relationship with microbial biomass and selected enzyme activities in soils with different origin,physical and chemical properties.Microbial degradation of total saponins ranged from 46%to 91%,according to soil characteristics,within 28 days from their incorporation into the soil.Both saponin glycosidic chains and triterpenic aglycones were also microbially degraded,though by dynamics changing among the different soils.In all soils,M.sativa saponins significantly reduced microbial biomass at rates of 10 and 20 mg saponin mixture per g of soil.Microbial enzymatic activities were less affected as indicating an adaptive response of soil microbial communities to the presence of saponins.展开更多
Forest planning involves estimating the biomass of species present in the area.Two fundamental parameters are diameter and height through which it is possible to indirectly estimate of biomass present.Digitalisation o...Forest planning involves estimating the biomass of species present in the area.Two fundamental parameters are diameter and height through which it is possible to indirectly estimate of biomass present.Digitalisation of forestry operations,such as forest planning,is crucial and should be affordable and easy-to-use digital applications and open-source devices.A digital progressive web application(PWA)was designed to record measurements.The app was connected via bluetoot to an open-source IoT digital forestry caliper prototyped by modifying a commercial tree caliper.An economic analysis was carried out considering all costs necessary for the development and operation of the app on smartphones and the preparation of electronic means for creation of the digital caliper.A comparison was made between costs of detecting tree diameters through application of the technology developed compared to costs calculated by applying the use of a dendrometric caliper(three technological levels were considered:L1,L2 and L3).The PWA allowed for easy data entry and viewing,maps and tree densities.The open-source digital caliper showed accuracy and precision comparable with similar commercial devices(1.5%±0.9%and 0.0%±0.9%,respectively).Total time per operator was lower using the digital caliper.From an economic perspective,application of the digital technology was more sustainable than the traditional system.Use of the digital caliper in combination with the web application optimizes detection time of a single tree,and therefore decreases overall cost.展开更多
AIM: To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method ...AIM: To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method to examine the effects of drinking and smoking habits against the levels of plasma 8-isoprostane in healthy Japanese volunteers.METHODS: Plasma 8-isoprostane was extracted with ODS gel suspension followed by NH2 Sep-Pak column. The 8-isoprostane fractions were assayed using a commercially available ELISA kit. We measured plasma 8-isoprostane levels in 157 healthy Japanese volunteers divided into three groups (64 non-habitual drinkers, 56 moderate drinkers and 37 habitual drinkers) according to their alcohol consumption per week. Genotypes of aldehyde dehydrogenase 2 (ALDH2) were also determined to investigate the plasma 8-isoprostane levels with reference to drinking habits. In addition, the plasma 8-isoprostane levels of 96 non-smokers and 61 smokers from the same subjects were compared.RESULTS: Our method fulfilled all the requirements for use in routine clinical assays with respect to sensitivity, intra- and inter-assay reproducibility, accuracy and dynamic assay range. Significant increases of plasma 8-isoprostane levels were observed in female habitual drinkers when compared with those of non-habitual drinkers (t = 5.494, P < 0.0001) as well as moderate drinkers (t = 3.542, P < 0.005), and 8-isoprostane levels were also significantly different between ALDH2*2/1 and ALDH2*1/1 in the female habitual drinkers (t = 6.930, P < 0.0001), suggesting that excessive drinking of alcohol may increase oxidization stress, especially in females. On the contrary, no significant difference of the plasma 8-isoprostane levels was observed between non-smokers and smokers.CONCLUSION: Our present method was proved to be a simple and accurate tool for measuring plasma 8-isoprostane. However, the clinical utility of plasma 8-isoprostane for drinking and smoking habits was limited since elevated 8-isoprostane levels were observed in female heavy drinkers, and no association was found between smokers and nonsmokers.展开更多
The aim of this study was to assess the effects of Sangrovit?, a standardized preparation of Macleaya cordata extract (MCE), on the health status and performance in weaned piglets. A total of 128 weaned piglets were r...The aim of this study was to assess the effects of Sangrovit?, a standardized preparation of Macleaya cordata extract (MCE), on the health status and performance in weaned piglets. A total of 128 weaned piglets were randomly divided into four groups (n = 32, 16/sex/group) and fed either a control feed (T1) or the control feed supplemented with 100 mg/kg (T2), 500 mg/kg (T3), or 1000 mg/kg (T4) Sangrovit? (resulting in 0, 3.5, 17.5, 35 mg MCE/kg feed, respectively) for ninety days. The parameters for growth and health status were evaluated during the trial and blood was collected on Day 0 and Day 91 for hematology and biochemistry analysis. After the animals were sacrificed, the weight of the major organs and tissues was measured and histopathological examination on the organs from 8 animals in each group (4/sex/group) was performed. The results showed no statistically significant differences in live weight, feed intake, and average daily weight gain between the treatment and control groups. The feed containing 100, 500, or 1000 mg/kg Sangrovit? was well tolerated by piglets, with no adverse effects noted during the feeding period or in the histopathological results. The majority of the hematological and blood biochemistry parameters displayed no significant changes between the control and treatment groups. Compared to the control group, some hematological parameters including MCV, platelets concentration, and APTT were modified in some but not all treatment groups. Some significant changes in the blood biochemistry parameters were found in the treatment groups including levels in bile acid, haptoglobin, total serum protein, and GTT, as well as creatine kinase activity, but those changes were not toxicologically significant because no observed changes were seen in other similar biomarkers. In sum, this study demonstrated that the addition of Sangrovit? to swine feed at up to 1000 mg/kg does not result in any toxicological effects to the health status and growth of weaned piglets.展开更多
Induction heating has been widely used by the heat treatment industry mainly in the wind-power and automotive sectors,in particular for hardening purposes,in a broad range of applications,its main advantages being the...Induction heating has been widely used by the heat treatment industry mainly in the wind-power and automotive sectors,in particular for hardening purposes,in a broad range of applications,its main advantages being the high repeatability and easy automation of the process,both factors leading to improved manufacturing efficiency and reduced CO;emissions.Though,traditional furnace-based case hardening treatments still represent the choice of reference when performance requirements are particularly demanding,either for the critical operating conditions or safety-related issues.The processes of CIH（Contour Induction Hardening）,compared to the traditional carburizing processes,allows to reduce the deformations after heat treatment.The main purpose of these treatments,as well as increases the surface hardness of the piece,is to induce compressive stresses in the superficial layer,improving the fatigue behavior.A multiphysics magneto-thermal simulation can be developed in order to calculate the temperature distribution in the gear,setting the input parameters such as currents,frequencies and treatment times.展开更多
Ethoxylation and propoxylation reactions are performed in the industry to produce mainly non-ionic surfactants and ethylene oxide(EO)–propylene oxide(PO) copolymers.Both the reactions occur in gas–liquid reactors by...Ethoxylation and propoxylation reactions are performed in the industry to produce mainly non-ionic surfactants and ethylene oxide(EO)–propylene oxide(PO) copolymers.Both the reactions occur in gas–liquid reactors by feeding gaseous EO,PO or both into the reactor containing a solution of an alkaline catalyst(KOH or Na OH).Non-ionic surfactants are produced by using liquid starters like fatty alcohols,fatty acids or alkyl-phenols,while when the scope is to prepare EO–PO copolymers the starter can be a mono-or multi-functional alcohol of low molecular weight.Both reactions are strongly exothermic,and EO and PO,in some conditions,can give place to runaway and also to explosive side reactions.Therefore,the choice of a suitable reactor is a key factor for operating in safe conditions.A correct reactor design requires:(i) the knowledge of the kinetic laws governing the rates of the occurring reactions;(ii) the role of mass and heat transfer in affecting the reaction rate;(iii) the solubility of EO and PO in the reacting mixture with the non-ideality of the reacting solutions considered;(iv) the density of the reacting mixture.All these aspects have been studied by our research group for different starters of industrial interest,and the data collected by using semibatch well stirred laboratory reactors have been employed for the simulation of industrial reactors,in particular Gas–Liquid Spray Tower Loop Reactors.展开更多
Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blo...Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.展开更多
AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the periphera...AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: ≤4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.展开更多
Forty seven clinical samples of Fowl adenovirus (FAdV) associated with Inclusion Body Hepatitis (IBH) from Peruvian broilers received between July 2006 and April 2013 were genotyped using sequencing of L1 Loop of Hexo...Forty seven clinical samples of Fowl adenovirus (FAdV) associated with Inclusion Body Hepatitis (IBH) from Peruvian broilers received between July 2006 and April 2013 were genotyped using sequencing of L1 Loop of Hexon gene. All 47 clinical samples presented macroscopic and histopathology lesions consistent with IBH, and amplified a specific fragment of Hexon gene by Polymerase Chain Reaction (PCR). A unique nucleotide sequence of 789 base pairs of Hexon gene (position 273 to 1061) was obtained in all 47 clinical samples analyzed. This sequence showed a high level of conservation in amino acid and nucleotide sequence (>99%) with a Fowl Adenovirus C serotype 4 previously identified. Sequence and phylogenetic analysis indicate no genotypic variation in Peruvian isolates. The presence of a unique genotype very closely related with genotype C1 previously reported in Peru and Ecuador (>99%), suggests the presence of FAdV C serotype 4 genotype C1 in clinical cases of IBH from Peruvian broilers.展开更多
The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove t...The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.展开更多
Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which...Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which is a bidirectional system between the central nervous system and the enteric nervous system.Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic,autoimmune,cancer,and,notably,neurodegenerative disorders.Diet can alter the microbiota composition,affecting the gutbrain axis function.Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions,including the use of probiotics.Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry,modulating different pathways.This review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy,confirming that gut microbiota modulation influences different pro-survival pathways.Future investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.展开更多
Reliable 3D modelling of underground hydrocarbon reservoirs is a challenging task due to the complexity of the underground geological formations and to the availability of different types of data that are typically af...Reliable 3D modelling of underground hydrocarbon reservoirs is a challenging task due to the complexity of the underground geological formations and to the availability of different types of data that are typically affected by uncertainties. In the case of geologically complex depositional environments, such as fractured hydrocarbon reservoirs, the uncertainties involved in the modelling process demand accurate analysis and quantification in order to provide a reliable confidence range of volumetric estimations. In the present work, we used a 3D model of a fractured carbonate reservoir and populated it with different lithological and petrophysical properties. The available dataset also included a discrete fracture network(DFN) property that was used to model the fracture distribution. Uncertainties affecting lithological facies, their geometry and absolute positions(related to the fault system), fracture distribution and petrophysical properties were accounted for. We included all different types of uncertainties in an automated approach using tools available in today’s modelling software packages and combining all the uncertain input parameters in a series of statistically representative geological realizations. In particular, we defined a specific workflow for the definition of the absolute permeability according to an equivalent, single porosity approach, taking into account the contribution of both the matrix and the fracture system. The results of the analyses were transferred into a 3D numerical fluid-dynamic simulator to evaluate the propagation of the uncertainties associated to the input data down to the final results, and to assess the dynamic response of the reservoir following a selected development plan. The "integrated approach" presented in this paper can be useful for all technicians involved in the construction and validation of 3D numerical models of hydrocarbon-bearing reservoirs and can potentially become part of the educational training for young geoscientists and engineers, since an integrated and well-constructed workflow is the backbone of any reservoir study.展开更多
文摘LOKIBASE is a non-linear isolator/dissipator device to protect pallet racking systems against the earthquake.LOKIBASE consists of the following main components:(1)two slider devices on which a rubber membrane is set up(LOKI devices).LOKI devices are linear displacement dependent ones;(2)a cylindrical beam damper(“CANDLE”device).The“CANDLE”device is a non-linear displacement dependent one;(3)two anti-lifting devices(“UP-LIFT”devices);(4)a fuse plug(see www.lokibasedevice.com).The main work which is the purpose of the paper,is the optimization of the behavior of an isolator/dissipator device to mitigate the seismic action on special structures,where the stiffness values are very different in the main cross-aisle and down-aisle directions.Under seismic action,in these structures it is very important to reduce the value of the forces at the Limit state for the safeguard of human life(SLV)in the down-aisle direction as much as possible and simultaneously to use the highest damping value allowed by the building rules to reduce the LOKIBASE displacement at the Limit state for collapse prevention(SLC)in the cross-aisle direction.The goal was achieved through a cylindrical device made of stainless steel(AISI304)with an optimized shape,under large displacement during seismic action.
文摘BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.
基金funded by the National Plan Military Research (EF a2011.188)
文摘Background:Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction.This was a sensitivity analysis of a drug(tetracosactide;TCS10)targeting melanocortin receptors(MCRs)in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.Methods:Sensitivity analysis was based on a randomized,two-arm,multicenter,double-blind,controlled trial.The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs outputs in 100 consecutive cases(from August to September 2013 from Emilia Romagna region,Italy).Patients included an agent-based TCS10 group(10 mg,single intravenous bolus before surgery;n=56)and control group(n=44)and the association with cytokines,lactate,and bleeding-blood transfusion episodes with the prior-risk log odds for mortality rate in time-to-event was analyzed.Results:Thirty-day mortality was significantly improved in the TCS10 group vs.control group(0 vs.8 deaths,P<0.0001).Baseline levels of interleukin(IL)-6,IL-10,and lactate were associated with bleeding episodes,independent of TCS10 treatment[odds ratio(OR)=1.90,95%confidence interval(CI)1.39-2.79;OR=1.53,95%CI 1.17-2.12;and OR=2.92,95%CI 1.40-6.66,respectively],while baseline level of Fms-like tyrosine kinase 3 ligand(Flt3L)was associated with lower bleeding rates in TCS10-treated patients(OR=0.31,95%CI 0.11-0.90,P=0.03).For every 8 TCS10-treated patients,1 bleeding case was avoided.Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group(OR=0.32,95%CI 0.14-0.73,P=0.01).For every 4 TCS10-treated patients,1 transfusion case was avoided.Conclusions:Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care.To introduce the technology readiness level in real-life critically ill patients,further large-scale studies are required.Trial registration:European Union Drug Regulating Authorities Clinical Trials Database(EudraCT Number:2007-006445-41).
基金supported by the ROP ERDF 2014-2020 Lombardy-Innovation and Competitiveness.
文摘Saponins can be potential candidates for the development of safe biopesticides,due to their widely acknowledged insecticidal,fungicidal and nematicidal activity,but information on their effects on soil biological properties is still limited.This study aimed to investigate the short-term fate of saponins from Medicago sativa in soil and their dose-effect relationship with microbial biomass and selected enzyme activities in soils with different origin,physical and chemical properties.Microbial degradation of total saponins ranged from 46%to 91%,according to soil characteristics,within 28 days from their incorporation into the soil.Both saponin glycosidic chains and triterpenic aglycones were also microbially degraded,though by dynamics changing among the different soils.In all soils,M.sativa saponins significantly reduced microbial biomass at rates of 10 and 20 mg saponin mixture per g of soil.Microbial enzymatic activities were less affected as indicating an adaptive response of soil microbial communities to the presence of saponins.
基金supported by the Italian Ministry of Agriculture,Ministry of Agriculture,Food Sovereignty and Forestry(MASAF),National program sub project Precision Forestry(AgriDigit program)(DM 36509.7305.2018 of 20/12/2018).
文摘Forest planning involves estimating the biomass of species present in the area.Two fundamental parameters are diameter and height through which it is possible to indirectly estimate of biomass present.Digitalisation of forestry operations,such as forest planning,is crucial and should be affordable and easy-to-use digital applications and open-source devices.A digital progressive web application(PWA)was designed to record measurements.The app was connected via bluetoot to an open-source IoT digital forestry caliper prototyped by modifying a commercial tree caliper.An economic analysis was carried out considering all costs necessary for the development and operation of the app on smartphones and the preparation of electronic means for creation of the digital caliper.A comparison was made between costs of detecting tree diameters through application of the technology developed compared to costs calculated by applying the use of a dendrometric caliper(three technological levels were considered:L1,L2 and L3).The PWA allowed for easy data entry and viewing,maps and tree densities.The open-source digital caliper showed accuracy and precision comparable with similar commercial devices(1.5%±0.9%and 0.0%±0.9%,respectively).Total time per operator was lower using the digital caliper.From an economic perspective,application of the digital technology was more sustainable than the traditional system.Use of the digital caliper in combination with the web application optimizes detection time of a single tree,and therefore decreases overall cost.
文摘AIM: To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method to examine the effects of drinking and smoking habits against the levels of plasma 8-isoprostane in healthy Japanese volunteers.METHODS: Plasma 8-isoprostane was extracted with ODS gel suspension followed by NH2 Sep-Pak column. The 8-isoprostane fractions were assayed using a commercially available ELISA kit. We measured plasma 8-isoprostane levels in 157 healthy Japanese volunteers divided into three groups (64 non-habitual drinkers, 56 moderate drinkers and 37 habitual drinkers) according to their alcohol consumption per week. Genotypes of aldehyde dehydrogenase 2 (ALDH2) were also determined to investigate the plasma 8-isoprostane levels with reference to drinking habits. In addition, the plasma 8-isoprostane levels of 96 non-smokers and 61 smokers from the same subjects were compared.RESULTS: Our method fulfilled all the requirements for use in routine clinical assays with respect to sensitivity, intra- and inter-assay reproducibility, accuracy and dynamic assay range. Significant increases of plasma 8-isoprostane levels were observed in female habitual drinkers when compared with those of non-habitual drinkers (t = 5.494, P < 0.0001) as well as moderate drinkers (t = 3.542, P < 0.005), and 8-isoprostane levels were also significantly different between ALDH2*2/1 and ALDH2*1/1 in the female habitual drinkers (t = 6.930, P < 0.0001), suggesting that excessive drinking of alcohol may increase oxidization stress, especially in females. On the contrary, no significant difference of the plasma 8-isoprostane levels was observed between non-smokers and smokers.CONCLUSION: Our present method was proved to be a simple and accurate tool for measuring plasma 8-isoprostane. However, the clinical utility of plasma 8-isoprostane for drinking and smoking habits was limited since elevated 8-isoprostane levels were observed in female heavy drinkers, and no association was found between smokers and nonsmokers.
文摘The aim of this study was to assess the effects of Sangrovit?, a standardized preparation of Macleaya cordata extract (MCE), on the health status and performance in weaned piglets. A total of 128 weaned piglets were randomly divided into four groups (n = 32, 16/sex/group) and fed either a control feed (T1) or the control feed supplemented with 100 mg/kg (T2), 500 mg/kg (T3), or 1000 mg/kg (T4) Sangrovit? (resulting in 0, 3.5, 17.5, 35 mg MCE/kg feed, respectively) for ninety days. The parameters for growth and health status were evaluated during the trial and blood was collected on Day 0 and Day 91 for hematology and biochemistry analysis. After the animals were sacrificed, the weight of the major organs and tissues was measured and histopathological examination on the organs from 8 animals in each group (4/sex/group) was performed. The results showed no statistically significant differences in live weight, feed intake, and average daily weight gain between the treatment and control groups. The feed containing 100, 500, or 1000 mg/kg Sangrovit? was well tolerated by piglets, with no adverse effects noted during the feeding period or in the histopathological results. The majority of the hematological and blood biochemistry parameters displayed no significant changes between the control and treatment groups. Compared to the control group, some hematological parameters including MCV, platelets concentration, and APTT were modified in some but not all treatment groups. Some significant changes in the blood biochemistry parameters were found in the treatment groups including levels in bile acid, haptoglobin, total serum protein, and GTT, as well as creatine kinase activity, but those changes were not toxicologically significant because no observed changes were seen in other similar biomarkers. In sum, this study demonstrated that the addition of Sangrovit? to swine feed at up to 1000 mg/kg does not result in any toxicological effects to the health status and growth of weaned piglets.
文摘Induction heating has been widely used by the heat treatment industry mainly in the wind-power and automotive sectors,in particular for hardening purposes,in a broad range of applications,its main advantages being the high repeatability and easy automation of the process,both factors leading to improved manufacturing efficiency and reduced CO;emissions.Though,traditional furnace-based case hardening treatments still represent the choice of reference when performance requirements are particularly demanding,either for the critical operating conditions or safety-related issues.The processes of CIH（Contour Induction Hardening）,compared to the traditional carburizing processes,allows to reduce the deformations after heat treatment.The main purpose of these treatments,as well as increases the surface hardness of the piece,is to induce compressive stresses in the superficial layer,improving the fatigue behavior.A multiphysics magneto-thermal simulation can be developed in order to calculate the temperature distribution in the gear,setting the input parameters such as currents,frequencies and treatment times.
文摘Ethoxylation and propoxylation reactions are performed in the industry to produce mainly non-ionic surfactants and ethylene oxide(EO)–propylene oxide(PO) copolymers.Both the reactions occur in gas–liquid reactors by feeding gaseous EO,PO or both into the reactor containing a solution of an alkaline catalyst(KOH or Na OH).Non-ionic surfactants are produced by using liquid starters like fatty alcohols,fatty acids or alkyl-phenols,while when the scope is to prepare EO–PO copolymers the starter can be a mono-or multi-functional alcohol of low molecular weight.Both reactions are strongly exothermic,and EO and PO,in some conditions,can give place to runaway and also to explosive side reactions.Therefore,the choice of a suitable reactor is a key factor for operating in safe conditions.A correct reactor design requires:(i) the knowledge of the kinetic laws governing the rates of the occurring reactions;(ii) the role of mass and heat transfer in affecting the reaction rate;(iii) the solubility of EO and PO in the reacting mixture with the non-ideality of the reacting solutions considered;(iv) the density of the reacting mixture.All these aspects have been studied by our research group for different starters of industrial interest,and the data collected by using semibatch well stirred laboratory reactors have been employed for the simulation of industrial reactors,in particular Gas–Liquid Spray Tower Loop Reactors.
基金Supported by Foundation“Ente Cassa di Risparmio di Firenze”,No.FCR 2017Italian Ministry of Health,Ricerca Finalizzata 2016,No.FR-2016-02361616。
文摘Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.
文摘AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: ≤4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.
文摘Forty seven clinical samples of Fowl adenovirus (FAdV) associated with Inclusion Body Hepatitis (IBH) from Peruvian broilers received between July 2006 and April 2013 were genotyped using sequencing of L1 Loop of Hexon gene. All 47 clinical samples presented macroscopic and histopathology lesions consistent with IBH, and amplified a specific fragment of Hexon gene by Polymerase Chain Reaction (PCR). A unique nucleotide sequence of 789 base pairs of Hexon gene (position 273 to 1061) was obtained in all 47 clinical samples analyzed. This sequence showed a high level of conservation in amino acid and nucleotide sequence (>99%) with a Fowl Adenovirus C serotype 4 previously identified. Sequence and phylogenetic analysis indicate no genotypic variation in Peruvian isolates. The presence of a unique genotype very closely related with genotype C1 previously reported in Peru and Ecuador (>99%), suggests the presence of FAdV C serotype 4 genotype C1 in clinical cases of IBH from Peruvian broilers.
基金This work was supported by the Romanian National Authority for Scientific Research and Innovation,CNCS-UEFISCDI[project number PN-III-P2-2.1-BG-2016-0201].
文摘The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.
文摘Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which is a bidirectional system between the central nervous system and the enteric nervous system.Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic,autoimmune,cancer,and,notably,neurodegenerative disorders.Diet can alter the microbiota composition,affecting the gutbrain axis function.Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions,including the use of probiotics.Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry,modulating different pathways.This review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy,confirming that gut microbiota modulation influences different pro-survival pathways.Future investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.
文摘Reliable 3D modelling of underground hydrocarbon reservoirs is a challenging task due to the complexity of the underground geological formations and to the availability of different types of data that are typically affected by uncertainties. In the case of geologically complex depositional environments, such as fractured hydrocarbon reservoirs, the uncertainties involved in the modelling process demand accurate analysis and quantification in order to provide a reliable confidence range of volumetric estimations. In the present work, we used a 3D model of a fractured carbonate reservoir and populated it with different lithological and petrophysical properties. The available dataset also included a discrete fracture network(DFN) property that was used to model the fracture distribution. Uncertainties affecting lithological facies, their geometry and absolute positions(related to the fault system), fracture distribution and petrophysical properties were accounted for. We included all different types of uncertainties in an automated approach using tools available in today’s modelling software packages and combining all the uncertain input parameters in a series of statistically representative geological realizations. In particular, we defined a specific workflow for the definition of the absolute permeability according to an equivalent, single porosity approach, taking into account the contribution of both the matrix and the fracture system. The results of the analyses were transferred into a 3D numerical fluid-dynamic simulator to evaluate the propagation of the uncertainties associated to the input data down to the final results, and to assess the dynamic response of the reservoir following a selected development plan. The "integrated approach" presented in this paper can be useful for all technicians involved in the construction and validation of 3D numerical models of hydrocarbon-bearing reservoirs and can potentially become part of the educational training for young geoscientists and engineers, since an integrated and well-constructed workflow is the backbone of any reservoir study.
