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Hepatic encephalopathy:An approach to its multiple pathophysiological features

World Journal of Hepatology 2012年第3期4卷 50-65页

作者： Juan Carlos Perazzo silvina Tallis Amalia Delfante pablo andrés souto Abraham Lemberg Francisco Xavier Eizayaga salvador Romay Laboratory of Portal Hypertensionand Hepatic Encephalopathy PathophysiologySchool of Pharmacy and BiochemistryUniversity of Buenos Aires Laboratory of Experimental Pathology School of MedicineUniversity of Buenos Aires Clinical Unit General Hospital I PirovanoGCBA

Hepatic encephalopathy(HE)is a neuropsychiatric complex syndrome,ranging from subtle behavioral abnormalities to deep coma and *** encephalopathy emerges as the major complication of acute or chronic liver *** of factors are involved in its pathophysiology,such as central and neuromuscular neurotransmission disorder,alterations in sleep patterns and cognition,changes in energy metabolism leading to cell injury,an oxidative/nitrosative state and a neuroinflammatory ***,in acute HE,a condition of imminent threat of death is present due to a deleterious astrocyte *** chronic HE,changes in calcium signaling,mitochondrial membrane potential and long term potential expression,N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations,and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be *** main molecule indicated as responsible for all these changes in HE is *** is no doubt that ammonia,a neurotoxic molecule,triggers or at least facilitates most of these *** plasma levels are increased two-to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite,glutamine(GLN),lead to hyperammonemic *** of hepatic ammonia is a differentiated work that includes the hepatocyte,through the urea cycle,converting ammonia into GLN via glutamine *** pathological conditions,such as liver damage or liver blood bypass,the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be *** editorial will focus on issues where, to the best of our knowledge,more research is needed in order to clarify,at least partially

关键词： Liver failure Hepatic encephalopathy Ammonia and central nervous system Hyperammonemia

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On the numerical solution to the truncated discrete sPH formulation of the hydrostatic problem

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Journal of Hydrodynamics 2020年第4期32卷 699-709页

作者： pablo Eleazar Merino-Alonso Fabricio Macia Antonio souto-Iglesias Mathematical Modeling Analysisand Simulation Applied to Engineering Research Group(M2ASAI)Universi dad politecnica de Madrid(UPM)School of marine engineering(ETSIN)MadridSpain Marine and Hydrodynamical Model Basin Research Group(CEHINAV) Universidad Politecnica de Madrid(UPM)School of Marine Engineering(ETSIN)MadridSpain

The aim of this work is to study the solution of the smoothed particle hydrodynamics(sPH)discrete formulation of the hydrostatic problem with a free *** problem,in which no time dependency is considered,takes the form of a system of linear *** particular,the problem in one dimension is *** focus is set on the convergence when both the particle spacing and the smoothing length tend to zero by keeping constant their *** of this ratio of the order of one,corresponding to a limited number of neighbors,are of practical ***,the problem in which each particle has one single neighbor at each side is *** explicit expressions of the numerical solution and the quadratic error are provided in this *** expression of the quadratic error demonstrates that the sPH solution does not converge to the exact one in general under the specified *** this case,the error converges to a residue,which is in general large compared to the norm of the exact *** cases with two and three neighbors are also *** analytical study in the case of two neighbors is performed,showing how the kernel influences the accuracy of the solution through modifying the condition number of the referred system of linear *** addition to that,a numerical investigation is carried out using several Wendland kernel *** two and three neighbors are involved it is found that the error tends in most cases to a small limiting value,different from zero,while divergent solutions are also found in the case of two neighbors with the Wendland Kernel *** cases with more neighbors are also *** general,the Wendland Kernel C2 turns out to be the worst choice,as the solution is divergent for certain values of the ratio between the particle spacing and the smoothing length,associated with an ill-conditioned matrix.

关键词： smoothed particle hydrodynamics(sPH) convergence water-at-rest problem hydrostatic tank,free surface kernel truncation

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Navigating medial patellotibial ligament reconstruction:Clinical perspectives and surgical strategies

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World Journal of Clinical Cases 2025年第1期13卷 6-10页

作者： Juan pablo Zicaro Ignacio Garcia-Mansilla Division of Knee Hospital Italiano de Buenos AiresBuenos Aires 1109Argentina

The surgical approach for patellar instability usually refers to reconstruction of the medial patellofemoral ligament associated with an osteotomy of the tibial tuberosity or a trochleoplasty when *** medial patellotibial ligament and the medial patellomeniscal ligament are secondary stabilizers of the *** this,both the medial patellotibial and patellofemoral ligaments aid in patellar rotation and tilt when the knee is flexed beyond 45°.The medial patellotibial ligament plays a particularly important role in the final stages of stretching in extension and between 40 degrees to 90 degrees of *** clinical relevance and surgical indications for medial patellotibial ligament reconstruction associated with medial patellofemoral ligament reconstruction are still *** editorial explores the surgical indications and clinical results for medial patellotibial ligament reconstruction to improve readers’understanding of this technique,especially because reported clinical outcomes have remained sparse.

关键词： Medial patellotibial ligament Patellar instability Reconstruction surgical

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ZigID:Improving visibility in industrial environments by combining WsN and RFID

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Journal of Zhejiang University-science A(Applied Physics & Engineering) 2011年第11期12卷 849-859页

作者： pablo GARCíA ANsOLA andrés GARCíA Javier de las MORENAs Javier GARCíA EsCRIBANO Francisco Javier OTAMENDI Autolog Labs School of Industrial EngineeringUniversity of Castilla-La Mancha Applied Economic Department University Rey Juan Carlos

The objective of this work is to provide decision-making processes with an updated/real picture of the mobile resources in industrial environments through a constant feedback of *** combination of identification technologies and wireless sensor networks(WsN) is proposed as a key development to guarantee an accurate and timely supply of online information regarding the localization and tracking of the mobile wireless *** approach uses a cooperative and distributed localization system,called ZigID,which is a WsN based on a Zigbee network with radio frequency identification(RFID) active tags as end *** WsN can recover not only the ID information stored at the tags attached to mobile resources,but also any other useful data captured by specific sensors for acceleration,temperature,humidity and fuel *** paper also shows the development of ZigID,including devices and information flows,as well as its implementation in ground handling operations at the Ciudad Real Central Airport,spain.

关键词： Radio frequency identification(RFID) Tracking Wireless sensor networks(WsNs)

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela seplovich Yazan Bouchi Juan pablo de Rivero Vaccari Jennifer C.Munoz Pareja andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse school of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Hepatic encephalopathy: Ever closer to its big bang

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World Journal of Gastroenterology 2016年第42期22卷 9251-9256页

作者： pablo A souto Ariel R Marcotegui Lisandro Orbea Juan skerl Juan Carlos Perazzo Department of Pathology Laboratory of Hyperammonemia and Hepatic Encephalopathy Center of Applied and Experimental Pathology Faculty of Medicine University of Buenos Aires

Hepatic encephalopathy(HE) is a neuropsychiatric disorder that commonly complicates the course of patients with liver disease. Despite the fact that the syndrome was probably first recognized hundreds of years ago, the exact pathogenesis still remains unclear. Minimal hepatic encephalopathy(MHE) is the earliest form of HE and is estimated to affect more that 75% of patients with liver cirrhosis. It is characterized by cognitive impairment predominantly attention, reactiveness and integrative function with very subtle clinical manifestations. The development of MHE is associated with worsen in driving skills, daily activities and the increase of overall mortality. skeletal muscle has the ability to shift from ammonia producer to ammonia detoxifying organ. Due to its large size, becomes the main ammonia detoxifying organ in case of chronic liver failure and muscular glutaminesynthase becomes important due to the failing liver and brain metabolic activity. Gut is the major glutamine consumer and ammonia producer organ in the body. Hepatocellular dysfunction due to liver disease, results in an impaired clearance of ammonium and in its interorgan trafficking. Intestinal bacteria, can also represent an extra source of ammonia production and in cirrhosis, small intestinal bacterial overgrowth and symbiosis can be observed. In the study of HE, to get close to MHE is to get closer to its big bang; and from here, to travel less transited roads such as skeletal muscle and intestine, is to go even closer. The aim of this editorial is to expose this road for further and deeper work.

关键词： Ammonia skeletal muscle Minimal hepatic encephalopathy Hyperammonemia

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旋转输运速度场积分sPH对流扩散方程解的收敛性

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Acta Mechanica sinica 2023年第2期39卷 61-70页

作者： pablo Eleazar Merino-Alonso Fabricio Macià Antonio souto-Iglesias Departamento de Arquitectura Constructión y Sistemas Oceánicos y NovalesUniversidad Politécnica de MadridMadridSpain Departamento de Matemática e Informática Aplicadas a las Ingenierías Civil y Naval Universidad Politécnica de MadridMadridSpain

本文在刚性旋转输运速度场的特殊情况下,建立了二维平流扩散方程的积分光滑粒子流体动力学(sPH)解的收敛性.考虑了Morris等人对拉普拉斯算子的近似,在傅里叶空间中建立了sPH解与精确解的收敛性.证明了如果满足核的傅里叶变换的某个条件... 详细信息

本文在刚性旋转输运速度场的特殊情况下,建立了二维平流扩散方程的积分光滑粒子流体动力学(sPH)解的收敛性.考虑了Morris等人对拉普拉斯算子的近似,在傅里叶空间中建立了sPH解与精确解的收敛性.证明了如果满足核的傅里叶变换的某个条件,即我们称之为正条件,则收敛是有保证的.这个条件是核的傅里叶变换其径向轮廓的一阶矩为正,并通过数值验证说明了分析结果.根据L2范数和最大范数,比较了使用不同核包括sPH社区更常用的核(即Wendland核以及三次和线性样条核)获得的数值解.除此之外,提出并测试了一个病理核,该核不满足正条件,导致了非收敛结果.这一事实表明,在对流扩散方程的情况下,正条件不仅是收敛的充分条件,也是必要条件.

关键词： smoothed particle hydrodynamics Numerical analysis Diffusion Convergence Fourier analysis

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Recent advances in graphene and other 2D materials

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Nano Materials science 2022年第1期4卷 3-9页

作者： pablo Ares Kostya s.Novoselov Department of Physics&Astronomy and National Graphene Institute University of ManchesterManchesterM139PLUK Centre for Advanced 2D Materials National University of Singapore117546Singapore Chongqing 2D Materials Institute Lingjiang New Area Chongqing 400714China

The isolation of the first two-dimensional material, graphene-a monolayer of carbon atoms arranged in a hexagonal lattice-opened new exciting opportunities in the field of condensed matter physics and materials. Its isolation and subsequent studies demonstrated that it was possible to obtain sheets of atomically thin crystals and that these were stable, and they also began to show its outstanding properties, thus opening the door to a whole new family of materials, known as two-dimensional materials or 2D materials. The great interest in different 2D materials is motivated by the variety of properties they show, being candidates for numerous ***, the combination of 2D crystals allows the assembly of composite, on-demand materials, known as van der Waals heterostructures, which take advantage of the properties of those materials to create functionalities that otherwise would not be accessible. For example, the combination of 2D materials, which can be done with high precision, is opening up opportunities for the study of new challenges in fundamental physics and novel applications. Here we review the latest fundamental discoveries in the area of 2D materials and offer a perspective on the future of the field.

关键词： 2D materials Graphene Molybdenum disulphide Tarition mebl dichalogenides Hexagonal boron nitride van der waals heterostructus Ulrathin nanomaterials

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Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1756-1762页

作者： sergio Hoyos pablo Posada-Moreno Natalia Guzman-Arango Romario Chanci-Drago Jaime Chavez Alvaro andrés-Duarte santiago salazar-Ochoa Hepatobilary and Liver Transplant Unit Hospital Pablo Tobon Uribe and Gastrohepathology Group Universidad de AntioquiaMedellin 050034AntioquiaColombia Department of General surgery Universidad Pontificia BolivarianaMedellín 050034AntioquiaColombia

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic *** can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related *** diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for ***,it is unclear whether managing these small tumors expectantly is truly *** To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm orsurgically treated *** This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,*** assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery *** variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of *** The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),*** involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in *** recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 *** survival was additionally comparable between the two tumor *** Tumor size does not dictate prognosis;lymph node and lymphovascular involvement a

关键词： Neuroendocrine tumor Pancreatic neoplasm Pancreas Pancreatic neuroendocrine neoplasm Pancreatic neuroendocrine tumors

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Predictive value of bleeding risk scores in elderly patients with atrial fibrillation and oral anticoagulation

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Journal of Geriatric Cardiology 2023年第9期20卷 684-692页

作者： pablo Domínguez-Erquicia sergio Raposeiras-Roubín Emad Abu-Assi andrea Lizancos-Castro Jose A Parada-Barcia andréGonzález-García Ana Ledo-Piñeiro Vanesa Noriega-Caro Carla Iglesias-Otero andrésÍñiguez-Romo Department of Cardiology University HospitalÁlvaro CunqueiroVigoSpain Health Research Institute Galicia sur VigoSpain

BACKGROUND The predictive value of bleeding risk scores for atrial fibrillation in older patients is not as well *** goal of this study was to evaluate the predictive value of HAsBLED,ORBIT and ATRIA for major bleeding(MB)and intracranial hemorrhage(ICH)in patients≥75 years with atrial fibrillation and oral anticoagulation(OAC).METHODs A retrospective unicenter study including patients≥75 years with atrial fibrillation(AF)and OAC.A total of 7613 patients≥75 years with AF and OAC included between 2014 and 2018(registry:NCT04364516).We analyzed the discriminative value of HAsBLED,ATRIA and ORBIT scores for bleeding endpoints(major bleeding as primary endpoint and intracerebral hemorrhage as secondary).Cox regression was used to predict major bleeding with each scale and also for searching other variables potentially predictor of major *** discrimination was assessed using Harrell’s *** was assessed with goodness-of-fit test proposed by Gronnesby and *** During a mean follow up of 4.0 years(IQR:2.4–5.7 years),729 patients developed MB(2.61 per 100 patients/year)and 243 patients developed ICH(0.85 per 100 patients/year).Three scores showed a low discrimination for major bleeding,being ORBIT the best(HAsBLED C statistic=0.557;ATRIA C statistic=0.568;ORBIT C statistic=0.595)and also a low discrimination for ICH(HAsBLED C statistic=0.509;ATRIA C statistic=0.522;ORBIT C statistic=0.526).Among the variables that are part of the scores and other baseline characteristics,after multivariable adjustment only sex(male),dementia,prior admission for bleeding,anemia and liver disease were found as a predictors of *** In older patients under oral anticoagulation with atrial fibrillation,the risk scores HAsBLED,ATRIA and ORBIT showed a weak discrimination for major bleeding and intracranial ***,other better alternatives should be evaluated for this purpose.

关键词： patients bleeding fibrillation

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