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Induced pluripotent stem cells for therapy personalization in pediatric patients:Focus on drug-induced adverse events

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World Journal of Stem Cells 2019年第12期11卷 1020-1044页

作者： Elena Genova Federica Cavion Marianna Lucafò Luigina De leo Marco Pelin Gabriele Stocco Giuliana Decorti PhD School in Reproduction and Development Sciences University of TriesteTrieste 34127Italy Department of Life Sciences University of TriesteTrieste 34127Italy Institute for Maternal and Child Health IRCCS Burlo GarofoloTrieste 34137Italy Department of Medical Surgical and Health SciencesUniversity of TriesteTrieste 34127Italy

Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric ***,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalization,disability or even *** addition,pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs,leading,in some cases,to more severe *** improve the comprehension,and thus the prevention,of ADRs,the set-up of sensitive and personalized assays is urgently *** progress is represented by the possibility of setting up groundbreaking patient-specific *** goal has been powerfully achieved using induced pluripotent stem cells(iPSCs).Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body,this model may be accurate in predicting drug toxicity,especially when this toxicity is related to individual genetic *** review is an up-to-date summary of the employment of iPSCs as a model to study ADRs,with particular attention to drugs used in the pediatric *** especially focused on the intestinal,hepatic,pancreatic,renal,cardiac,and neuronal levels,also discussing progress in organoids *** latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine,liver,pancreas,kidney,heart,and *** on the existing knowledge,these models are powerful and promising tools in multiple clinical applications including toxicity screening,disease modeling,personalized and regenerative medicine.

关键词： Induced pluripotent stem cells Organoids Adverse drug reactions Intestinal toxicity Hepatic toxicity Pancreatic toxicity Nephrotoxicity Cardiotoxicity Neurotoxicity

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Using fuzzy-AHP and parametric technique to assess soil fertility status in Northeast of Iran

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Journal of Mountain Science 2020年第4期17卷 931-948页

作者： Ali KESHAVARZI Henry Oppong TUFFOUR Ali BAGHERZADEH leo Paapa TATTRAH Vinod KUMAR Amin GHOLIZADEH Jesús RODRIGO-COMINO Laboratory of Remote Sensing and GIS Department of Soil ScienceUniversity of TehranKaraj 31587-77871Iran Department of Mining Engineering Hacettepe University06800 BeytepeAnkaraTurkey Department of Crop and Soil Sciences Kwame Nkrumah University of Science and TechnologyKumasi 00233Ghana Department of Agriculture Islamic Azad UniversityMashhad BranchP.O.Box:91735-413Mashhad 91735-413Iran Department of Computer Science Kumasi Technical UniversityKumasi 00233Ghana Government Degree College Ramban-182144 Jammu and KashmirIndia Physical Geography Trier University54286 TrierGermany Soil Erosion and Degradation Research Group.Department of Geography Valencia UniversityBlasco Ibànez2846010 ValenciaSpain

A good understanding of the levels and distribution patterns of soil properties and/or quality indicators is a prerequisite for developing sustainable agricultural land management programs. Traditional assessments of these parameters of soil fertility status are somewhat costly, in both economics and time aspects. Different modelling techniques have been proposed as a useful tool for determination of soil quality indicators and development of soil fertility maps, but to what extent these results are reliable remains under-quantified in many regions worldwide. To address this uncertainty, Fuzzy-Analytical Hierarchy Process(Fuzzy-AHP) and Parametric analyses were conducted to ascertain the soil fertility status of a semiarid region in the Northeast of Iran for some selected crops: alfalfa, corn silage, potato, sugar beet, tomato and wheat. The Fuzzy-AHP and Parametric techniques using soil suitability indices were estimated for each crop and each soil delineation was achieved by Ordinary Kriging. The Technique for Order of Preference by Similarity to Ideal Solution(TOPSIS) was used as a compensatory method to allow tradeoffs among the selected criteria. Our results demonstrated that from the Fuzzy-AHP analysis, the soil fertility indices ranged from moderate to high for production of alfalfa;from low to high for production of corn silage and sugar beet;moderate to high for production of potato and tomato;and from low to moderate for production of wheat. However, the parametric analysis showed soil fertility classes ranging from very low to high for production of all the selected crops. High correlations were also observed between soil fertility indices predicted by both models. Similarly, the capacities of both models to predict soil fertility status for production of the selected crops were also highly correlated. The preference for the cultivation of the selected crops based on the Fuzzy-AHP analysis was sugar beet > corn silage > wheat > alfalfa > tomato > potato.

关键词： Soil fertility Agricultural land management Parametric model Geographic information systems Analytic Hierarchy Process

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Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm

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World Journal of Gastroenterology 2018年第14期24卷 1521-1530页

作者： Giuseppe Losurdo Mariabeatrice Principi Andrea Iannone Annacinzia Amoruso Enzo Ierardi Alfredo Di leo Michele Barone Section of Gastroenterology Department of Emergency and Organ Transplantation University "Aldo Moro" of Bari

Non celiac gluten sensitivity(NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease(CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders(irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal

关键词： Non celiac gluten sensitivity celiac disease gluten gluten ataxia autoimmunity gluten-related disorders thyroiditis extra-intestinal

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Carbon monoxide contributes to the constipating effects of granisetron in rat colon

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World Journal of Gastroenterology 2016年第42期22卷 9333-9345页

作者： Carmela Nacci Margherita Fanelli Maria Assunta Potenza Valentina leo Monica Montagnani Maria Antonietta De Salvia Department of Biomedical Sciences and Human Oncology - Pharmacology Section Medical School University of Bari "Aldo Moro" Department of Interdisciplinary Medicine Medical School University of Bari "Aldo Moro"

AIM To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide(HO/CO) pathway in the constipating effects of granisetron. METHODS For in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous(sc)], zinc protoporphyrin IX [Zn PPIX, 50 μg/kg/intraperitoneal(ip)] and hemin(50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation(EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine(ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron(3 μmol/L, 15 min), Zn PPIX(10 μmol/L, 60 min) or CO-releasing molecule-3(CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment withor without atropine(3 μmol/L, a muscarinic receptor antagonist) or NG-nitro-L-Arginine(L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor).RESULTS Administration of granisetron(50, 75 μg/kg) in vivo significantly increased the time to first defecation(P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of Zn PPIX or hemin alone had no effect on this gastrointestinal motility parameter, Zn PPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro, granisetron alone(3 μmol/L) did not significantly modify the colon's contractile response to either EFS or ACh. Incubation with Zn PPIX alone(10 μmol/L) significantly reduced the colon's contractile response to EFS(P = 0.016) but had no effect on contractile response to ACh. Co-administration of Zn PPIX and atropine(3 μmol/L) abolished the Zn PPIX-mediated decrease in contrac

关键词： Granisetron Carbon monoxide Heme oxygenase Colon Contraction Neurogenic response Myogenic response

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Optimizing proton pump inhibitors in Helicobacter pylori treatment:Old and new tricks to improve effectiveness

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World Journal of Gastroenterology 2019年第34期25卷 5097-5104页

作者： Enzo Ierardi Giuseppe Losurdo Rosa Federica La Fortezza Mariabeatrice Principi Michele Barone Alfredo Di leo Section of Gastroenterology Department of Emergency and Organ Transplantation University of Bari

The survival and replication cycle of Helicobacter pylori(***)is strictly dependant on intragastric pH,since *** enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to *** these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be ***,several tricks need to be used to optimize eradication rate of different *** administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is ***,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic ***,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic *** current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.

关键词： Helicobacter pylori Proton pump inhibitors Eradication Cytochrome P450 Optimization

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Margin Debt： Upcoming Trigger for a Bear Run？

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China International Business 2015年第6期 56-57页

作者： leo ZHANG Deputy Editor in Chiefat Shanghai Daily

＂News related to any curb on margin debt could have a big impact on the market, as people conceive it as a signal of tightening.＂

关键词：保证金引发债务

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Atomic and electronic structure of Si dangling bonds in quasi-free-standing monolayer graphene

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Nano Research 2018年第2期11卷 864-873页

作者： Yuya Murata Tommaso Cavallucci Valentina Tozzini Niko Pavliček leo Gross Gerhard Meyer Makoto Takamura Hiroki Hibino Fabio Beltram Stefan Heun NEST Istituto Nanoscienze-CNR and Scuola Normale Superiore Pisa Italy IBM Research-Zurich Rüschlikon Switzerland NTT Basic Research Laboratories Atsugi Kanagawa Japan

Si dangling bonds at the interface of quasi-free-standing monolayer graphene （QFMLG） are known to act as scattering centers that can severely affect carrier mobility Herein, we investigate the atomic and electronic structure of Si dangling bonds in QFMLG using low-temperature scanning tunneling microscopy/ spectroscopy （STM/STS）, atomic force microscopy （AFM）, and density functional theory （DFT） calculations. Two types of defects with different contrast were observed on a flat graphene terrace by STM and AFM; in particular, their STM contrast varied with the bias voltage. Moreover, these defects showed characteristic STS peaks at different energies, 1.1 and 1.4 eV. The comparison of the experimental data with the DFT calculations indicates that the defects with STS peak energies of 1.1 and 1.4 eV consist of clusters of three and four Si dangling bonds, respectively. The relevance of the present results for the optimization of graphene synthesis is discussed.

关键词： quasi-free-standingmonolayer graphene hydrogen intercalation carrier mobility scanning tunnelingmicroscopy scanning tunnelingspectroscop^atomic force microscop3~density functional theory

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Impact of indoor heat load and natural ventilation on thermal comfort of radiant cooling system:An experimental study

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Energy and Built Environment 2023年第5期4卷 543-556页

作者： K Dharmasastha D.G.leo Samuel S.M.Shiva Nagendr M.P.Maiya Department of Mechanical Engineering Indian Institute of Technology MadrasChennaiTamil Nadu 600036India Barghest Building Performance Pte.Ltd. 118535Singapore Department of Civil Engineering Indian Institute of Technology MadrasRefrigeration and Air ConditioningChennai 600036India Department of Building Enivironment and Energy Engineering The Hong Kong Polytechnic UniversityHong Kong

Construction and operation of buildings are responsible for about 20%of the global energy *** embodied energy of conventional buildings is high due to the utilization of energy-intensive construction mate-rials and traditional construction *** operational energy is attributed to the usage of power-consuming conventional air-conditioning ***,moving to an energy-efficient cooling technology and eco-friendly building material can lead to significant energy savings and CO 2 emission *** the present study,an energy-efficient thermally activated building system(TABS)is integrated with glass fiber rein-forced gypsum(GFRG),an eco-friendly building *** proposed hybrid system is termed the thermally activated glass fiber reinforced gypsum(TAGFRG)*** system is not only energy-efficient and eco-friendly but also provides better thermal *** experimental room with a TAGFRG roof is constructed on the premises of the Indian Institute of Technology Madras(IITM),Chennai,located in a tropical wet and dry climate *** influence of indoor sensible heat load and the impact of natural ventilation on the thermal comfort of the TAGFRG system are *** increase in internal heat load from 400 to 700 W deteriorates the thermal comfort of the indoor *** is evident from the increases in operative temperatures from 29.8 to 31.5℃ and the predicted percentage of dissatisfaction from 44.5%to 80.9%.Natural ventilation increases the diurnal fluctuation of indoor air temperature by 1.6 and 1.9℃ for with and without cooling cases,*** reduces the maximum indoor CO 2 concentration from 912 to 393 ppm.

关键词： Thermally activated building system Air-conditioning Natural ventilation Thermal comfort Indoor air quality

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Global Yuan Push Gains Currenc!

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China International Business 2012年第12期 21-23页

作者： leo ZHANG

China＇s initiative to internationalize ,the yuan is set to enter a new level, with the currency＇s strong perfor mance this year reviving yuan-backed offshore bond issuance and business start- ing to regain momentum in the Western Hemisphere. China Construction Bank Corp., the nation＇s No.2 lender by market value, in November became the first mainland com- pany to sell the offshore yuan-denominatedbond, better known as Dim Sum debt, in London, and plans to use the proceeds to develop its overseas yuan business.

关键词：中国建设银行人民币国际化债券创业股份贷款出售

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Steady Economic Policy for the Benefit of Domestic Consumption

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China International Business 2013年第1期 8-11页

作者： leo ZHANG

China＇s top leaders have drawn up a blueprint for the economy in 2013, which envisages sustaining the recovery by maintaining policy stability and bolstering domestic consumption to counter the lingering weakness in ... 详细信息

关键词：经济复苏消费政策稳定性国内效益领导人

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