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Intense pulsed light‑based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops

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Eye and Vision 2024年第2期10卷 12-21页

作者： Jose Maria Martinez‑de‑la‑Casa Carlos Oribio‑Quinto Almudena Milans‑del‑Bosch Pilar Perez‑garcia Laura Morales‑Fernandez Javier garcia‑Bella Jose manuel Benitez‑del‑Castillo Julian garcia‑Feijoo David P.Pinero Ophthalmology Unit Department of Ophthalmology and ORLFaculty of MedicineHospital Clinico San-CarlosUniversidad Complutense de MadridInstituto de Investigacion Sanitaria del Hospital Clinico San-Carlos(IdISSC)28040 MadridSpain Department of Immunology Ophthalmology and ORLSchool of MedicineInstituto de Investigaciones Oftalmologicas Ramon CastroviejoUniversidad Complutense de MadridMadridSpain Department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicanteSpain

Background:Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40%to 59%of these patients worldwide.The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light(IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments.To our knowledge,this is the first series analyzing the therapeutic effect of this treatment option in this type of patients.Methods:This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology.All patients received four sessions of IPL treatment using the Optima IPL system(Lumenis,Yokneam,Israel)adjusted to the official optimized Lumenis setting.Changes in symptomatology,corneal staining,conjunctival hyperemia,non-invasive break-up time(NIBUT),tear osmolarity,tear meniscus height(TMH),meiboscore and meibomian gland expressibility was analyzed after treatment.Results:Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires[ocular surface disease index(OSDI),standard patient evaluation of eye dryness(SPEED)and symptom assessment questionnaire in dry eye(SANDE)]as well as with the visual analogue scale(Pge in OSDI was−15.0±11.3.A significant reduction was found after treatment in the corneal staining score(Pgnificant reduction was found in tear film meniscus height(P=0.012),as well as in tear film osmolarity(P=0.001).A significant reduction was also found in meibomian gland expressibility(P=0.003),changing the percentage of grade 3 eyes from 44.4%before IPL to 17.2%after treatment.Conclusions:IPL therapy combined with meibomian gland expression(MgX)seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatment

关键词： glaucoma Intense pulsed light Dry eye Meibomian glands

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Dissecting the molecular pathophysiology of drug-induced liver injury

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World Journal of gastroenterology 2018年第13期24卷 1373-1385页

作者： Hui Ye Leonard J Nelson manuel gómez del Moral Eduardo Martínez-Naves Francisco Javier Cubero Department of Immunology Ophtalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain Institute for BioEngineering(Human Liver Tissue Engineering Faraday BuildingThe University of EdinburghThe King BuildingsMayfield RoadEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Cell Biology Complutense University School of MedicineMadrid 28040Spain

Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways.

关键词： signaling pathways acetaminophen Drug-induced liver injury cell death reactive oxygen species

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Why is early detection of colon cancer still not possible in 2023?

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World Journal of gastroenterology 2024年第3期30卷 211-224页

作者： Valeria Tonini manuel Zanni Department of Medical and Surgical Sciences University of BolognaBologna 40138Italy

Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well organized,has succeeded in reducing the incidence of colon and rectal cancer and improving the prognosis related to them.Despite considerable advancements in screening technologies and strategies,the effectiveness of CRC screening programs remains less than optimal.This paper examined the multifaceted reasons behind the persistent lack of effect-iveness in CRC screening initiatives.Through a critical analysis of current methodologies,technological limitations,patient-related factors,and systemic challenges,we elucidated the complex interplay that hampers the successful reduction of CRC morbidity and mortality rates.While acknowledging the ad-vancements that have improved aspects of screening,we emphasized the necessity of addressing the identified barriers comprehensively.This study aimed to raise awareness of how important CRC screening is in reducing costs for this disease.Screening and early diagnosis are not only important in improving the prognosis of patients with CRC but can lead to an important reduction in the cost of treating a disease that is often diagnosed at an advanced stage.Spending more sooner can mean saving money later.

关键词： Colorectal cancer Colorectal cancer screening Colorectal screening test Colon and rectal cancer

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The Pichia pastoris enzyme production platform:From combinatorial library screening to bench-top fermentation on residual cyanobacterial biomass

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Journal of Bioresources and Bioproducts 2024年第1期9卷 43-57页

作者： Korbinian Sinzinger Ulrike Obst Samed güner manuel Döring Magdalena Haslbeck Doris Schieder Volker Sieber Chair of Chemistry of Biogenic Resources Campus Straubing for Biotechnology and SustainabilityTechnical University of MunichStraubing 94315Germany Catalysis Research Center Technical University of MunichGarching 85748Germany SynBiofoundry@TUM Technical University of MunichStraubing 94315Germany School of Chemistry and Molecular Biosciences The University of QueenslandSt.Lucia 4072Australia

The demand for industrial enzymes is continually rising,fueled by the growing need to shift towards more sustainable industrial processes.However,making efficient enzyme production strains and identifying optimal enzyme expression conditions remains a challenge.Moreover,the production of the enzymes themselves comes with unavoidable impacts,e.g.,the need to utilize secondary feedstocks.Here,we take a more holistic view of bioprocess development and report an integrative approach that allows us to rapidly identify improved enzyme expression and secretion conditions and make use of cyanobacterial waste biomass as feed for supporting Pichia pastoris fermentation.We demonstrate these capabilities by producing a phytase secreted by P.pastoris that is grown on cyanobacterium hydrolysate and buffered glycerol-complex(BMgY)medium,with genetic expression conditions identified by high-throughput screening of a randomized se-cretion library.When our best-performing strain is grown in a fed-batch fermentation on BMgY,we reach over 7000 U/mL in three days.

关键词： Protein secretion Phytase Cyanobacterial biomass Fed-batch fermentation Pichia pastoris

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Tracking the change in Spanish greenhouse gas emissions through an LMDI decomposition model:A global and sectoral approach

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Journal of Environmental Sciences 2024年第5期139卷 114-122页

作者： Paula Fernández gonzález María José Presno manuel Landajo Department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of gHg emissions to reverse the greenhouse effect is one of the main challenges in this century.In this paper we pursue two objectives.First,we analyze the evolution of gHg emissions in Spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining factors.Second,we propose several actions specifically oriented to more tightly controlling the level of emissions.Our results showed a remarkable reduction(18.44%)in gHg emissions,mainly due to the intensity effect,but also to the production-per-capita effect.We detected somewhat different patterns among the various sectors analyzed.While the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of industry.The carbonization effect was revealed as crucial in the commerce sector.The above findings highlight the importance of the energy efficiency measures taken in recent years in the Spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in emissions.Additional efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： LMDI Decomposition Spain gHg emissions

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Alcoholic liver disease:Utility of animal models

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World Journal of gastroenterology 2018年第45期24卷 5063-5075页

作者： Arantza Lamas-Paz Fengjie Hao Leonard J Nelson Maria Teresa Vázquez Santiago Canals manuel gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco Javier Cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain Institute for Bioengineering(IBioE) School of EngineeringFaraday BuildingThe University of EdinburghEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Human Anatomy and Embryology Complutense University School of MedicineMadrid 28040Spain Instituto de Neurociencias Consejo Superior de Investigaciones CientíficasUniversidad Miguel HernándezSan Juan de Alicante 03550Spain Department of Cell Biology Complutense University School of MedicineMadrid 28040Spain Department of genetics Physiology and MicrobiologyFaculty of BiologyUniversidad ComplutenseMadrid 28040Spain Department of Internal Medicine Ⅲ University Hospital RWTH AachenAachen 52062Germany

Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

关键词： Steatohepatitis Cirrhosis Hepatocellular carcinoma Alcoholic liver disease Reactive oxygen species

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genome-resolved metagenomics of Venice Lagoon surface sediment bacteria reveals high biosynthetic potential and metabolic plasticity as successful strategies in an impacted environment

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Marine Life Science & Technology 2024年第1期6卷 126-142页

作者： Elisa Banchi Erwan Corre Paola del Negro Mauro Celussi Francesca Malfatti National Institute of Oceanography and Applied geophysics OgS TriesteItaly FR2424 Station Biologique de RoscoffPlateforme ABiMS(Analysis and Bioinformatics for Marine Science)Sorbonne Universite CNRS29680 RoscoffFrance Department of Life Sciences University of TriesteTriesteItaly

Bacteria living in sediments play essential roles in marine ecosystems and deeper insights into the ecology and biogeochemistry of these largely unexplored organisms can be obtained from‘omics’approaches.Here,we characterized metagenome-assembled-genomes(MAgs)from the surface sediment microbes of the Venice Lagoon(northern Adriatic Sea)in distinct sub-basins exposed to various natural and anthropogenic pressures.MAgs were explored for biodiversity,major marine metabolic processes,anthropogenic activity-related functions,adaptations at the microscale,and biosynthetic gene clusters.Starting from 126 MAgs,a non-redundant dataset of 58 was compiled,the majority of which(35)belonged to(Alpha-and gamma-)Proteobacteria.Within the broad microbial metabolic repertoire(including C,N,and S metabolisms)the potential to live without oxygen emerged as one of the most important features.Mixotrophy was also found as a successful lifestyle.Cluster analysis showed that different MAgs encoded the same metabolic patterns(e.g.,C fixation,sulfate oxidation)thus suggesting metabolic redundancy.Antibiotic and toxic compounds resistance genes were coupled,a condition that could promote the spreading of these genetic traits.MAgs showed a high biosynthetic potential related to antimicrobial and biotechnological classes and to organism defense and interactions as well as adaptive strategies for micronutrient uptake and cellular detoxification.Our results highlighted that bacteria living in an impacted environment,such as the surface sediments of the Venice Lagoon,may benefit from metabolic plasticity as well as from the synthesis of a wide array of secondary metabolites,promoting ecosystem resilience and stability toward environmental pressures.

关键词： Antibiotic resistance PAHs Biosynthetic gene clusters Microscale Mobilome Resistome

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Advancing hepatic recompensation:Baveno VII criteria and therapeutic innovations in liver cirrhosis management

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World Journal of gastroenterology 2024年第23期30卷 2954-2958页

作者： Lorenzo Ridola Sara del Cioppo Department of Medical and Surgical Sciences and Biotechnologies Sapienza University of RomePolo PontinoRome 00185Italy

The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies,including antivirals and lifestyle modifications.Studies on alcohol,hepatitis C virus,and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes.Transjugular intrahepatic portosystemic shunt(TIPS)emerges as a promising intervention,effectively resolving complications of portal hypertension and facilitating recompensation.However,optimal timing and patient selection for TIPS remain unresolved.Despite challenges,TIPS offers renewed hope for hepatic recompensation,marking a significant advancement in cirrhosis management.Further research is needed to refine its implementation and maximize its benefits.In conclusion,TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.

关键词： Hepatic recompensation Baveno VII Transjugular intrahepatic portosystemic shunt Portal hypertension Cirrhosis Decompensation

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Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management:delphi consensus study

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World Journal of gastroenterology 2024年第18期30卷 2467-2478页

作者： Edda Battaglia Luciano Bertolusso Marco del Prete Marco Monzani Marco Astegiano gastroenterology Unit ASLTO4Ivrea 10015TurinItaly general Practitioner ASL CN2Alba-Bra 12051CuneoItaly Specialist in Nephrology International Academy of Physiological Regulating Medicine Milan 20100Italy Specialist in Endocrinology Territorial Social and Health Authority of BrianzaMonza 20900Italy gastroenterology Specialist Retired from Gastroenterology and Hepatology UnitAOU Cittàdella Salute e della ScienzaTurin 10123Italy

BACKgROUND gastro-esophageal reflux disease(gERD)may affect the upper digestive tract;up to 20%of population in Western nations are affected by gERD.Antacids,histamine H2-receptor antagonists,and Proton Pump Inhibitors(PPIs)are considered the referring medications for gERD.Nevertheless,PPIs must be managed carefully because their use,especially chronic,could be linked with some adverse effects.An effective and safe alternative pharmacological tool for gERD is needed.After the identification of potentially new medications to flank PPIs,it is mandatory to revise and improve good clinical practices even through a consensus process.AIM To optimize diagnosis and treatment guidelines for gERD through a consensus based on delphi method.METHODS The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel,subject of the consensus,is the basic prerequisite for the consensus itself.A modified delphi process was used to reach a consensus among a panel of Italian gERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of gERD.The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations:gastroenterology,otolaryngology,geriatrics,and general medicine.A scientific committee analyzed the literature,determined areas that required investigation(in agreement with the multiple-choice questionnaire results),and identified two topics of interest:(1)gERD disease;and(2)gERD treatment.Statements for each of these topics were then formulated and validated.The delphi process involved two rounds of questioning submitted to the panel experts using an online platform.RESULTS According to their routinary gERD practice and current clinical evidence,the panel members provided feedback to each questionnaire statement.The experts evaluated 15 statements and reached consensus on all 15.The statements regarding the gERD disease showed high levels of agreement,with consensus ranging from 70%to 92%.

关键词： gastro-esophageal reflux disease Proton Pump Inhibitors Consensus Nux vomica-Heel Overlapping Decalage

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The Role of the Spatial Network in Urban Disaster Risk Variations:Reimagining the Notion of Spatial Vulnerability at the Urban Scale

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International Journal of Disaster Risk Science 2024年第3期15卷 303-316页

作者： Monia del Pinto Ksenia Chmutina Falli Palaiologou Lee Bosher School of Architecture Building and Civil Engineering Loughborough University School of Business University of Leicester

The notion of “spatial vulnerability” is present in most disaster studies with a strong geographical connotation and accordingly is adopted at all scales, including the urban. While enabling mapping and visualizing risk patterns at macroscales, this geocentric foundation fails to capture disaster risk dynamics associated with the urban spatial network—an element that plays a significant role in the everyday and emergency functioning of cities, enabling users' movement and interaction. Yet,urban vulnerability assessment overlooks this aspect and thus leaves urban disaster risk mechanisms partially unexplored.This study investigated the role of the network of urban public open spaces(UPOS) in the creation and progression of urban disaster risk in earthquake-prone settlements. Through a multimethod approach that integrates quantitative and qualitative methods and explores spatial configuration, planning policies, and practices of use of UPOS in everyday and emergency scenarios, our study demonstrated that UPOS configuration plays an active role in urban disaster risk. Urban public open spaces impact risk by influencing the exposure of pedestrians and their capacity for self-protection. The study further reconceptualized spatial vulnerability at the urban scale, as the fraction of vulnerability associated to the spatial network, highlighting the interplay of planning policies and spatial practices in its production and progression. Our findings make the notion of spatial vulnerability less ambiguous at the urban scale, by viewing the variable as an imbalance in capacities and exposure that generates spatially unsafe conditions. This refined conceptualization of spatial vulnerability becomes a lens for a more granular approach to urban disaster risk reduction and city planning by identifying and integrating sociospatial considerations.

关键词： Central Italy Earthquakes Pedestrian evacuation Space syntax Spatial vulnerability Urban disaster risk

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