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Managing end-stage carcinoid heart disease:A case report and literature review

World Journal of Gastrointestinal Oncology 2024年第3期16卷 1076-1083页

作者： nikola Bulj Vedran Tomasic Maja Cigrovski Berkovic Department of Cardiology University Hospital Centre“Sestre Milosrdnice“Zagreb 10000Croatia Division of Gastroenterology Department of Internal MedicineUniversity Hospital Centre“Sestre Milosrdnice”Zagreb 10000Croatia Department for sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of life.Cardiovascular complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic disease.CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases.During the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to follow-up.After 10 years,he presented to the emergency room with signs and symptoms of right-sided heart failure.Panneuroendocrine markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic metastases.Computed tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis.Furthermore,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart disease.The patient was not a candidate for valve replacement.He started octreotide acetate treatment,and the dose escalated to 80 mg IM monthly.Although biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart failure.Carcinoid heart disease and tumor burden are major prognostic factors of poor survival.Therefore,they must be actively sought by avai

关键词： Gastroenteropancreatic neuroendocrine neoplasms Carcinoid syndrome Carcinoid heart disease Diagnosis Treatment Case report

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An in vitro demonstration of a passive,acoustic metamaterial as a temperature sensor with mK resolution for implantable applications

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Microsystems & Nanoengineering 2024年第1期10卷 41-54页

作者： Lucrezia Maini Vicente Genovés Roman Furrer nikola Cesarovic Christofer Hierold Cosmin Roman Micro-and Nanosystems Department of Mechanical and Process EngineeringETH ZurichTannenstrasse 38092 ZurichSwitzerland. Translational Cardiovascular Technology Department of Health Science and TechnologyETH ZurichLeopold-Ruzicka-Weg 48093 ZurichSwitzerland. Transport at Nanoscale Interfaces Swiss Federal Laboratories for Materials Science and TechnologyEMPAÜberlandstrasse 1298600 DübendorfSwitzerland Department of Cardiothoracic and Vascular Surgery Deutsches Herzzentrum der Charite(DHZC)13353 BerlinGermany

Wireless medical sensors typically utilize electromagnetic coupling or ultrasound for energy transfer and sensor interrogation.Energy transfer and management is a complex aspect that often limits the applicability of implantable sensor systems.In this work,we report a new passive temperature sensing scheme based on an acoustic metamaterial made of silicon embedded in a polydimethylsiloxane matrix.Compared to other approaches,this concept is implemented without additional electrical components in situ or the need for a customized receiving unit.A standard ultrasonic transducer is used for this demonstration to directly excite and collect the reflected signal.The metamaterial resonates at a frequency close to a typical medical value(5 MHz)and exhibits a high-quality factor.Combining the design features of the metamaterial with the high-temperature sensitivity of the polydimethylsiloxane matrix,we achieve a temperature resolution of 30 mK.This value is below the current standard resolution required in infrared thermometry for monitoring postoperative complications(0.1 K).We fabricated,simulated,in vitro tested,and compared three acoustic sensor designs in the 29-43℃(~302-316 K)temperature range.With this concept,we demonstrate how our passive metamaterial sensor can open the way toward new zero-power smart medical implant concepts based on acoustic interrogation.

关键词： passive resolution utilize

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Treatment endpoints in ulcerative colitis:Does one size fit all?

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2024年第2期15卷 1-12页

作者： nikola Mitrev Viraj Kariyawasam Department of Gastroenterology Blacktown HospitalBlacktown 2148NSWAustralia Blacktown/Mt Druitt Clinical School University of Western SydneyBlacktown 2148NSWAustralia Department of Gastroenterology Wollongong HospitalLoftus StWollongong 2500NSWAustralia

A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms.However,choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy.The treatment endpoints for ulcerative colitis(UC),recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)consensus have changed somewhat over time.The latest STRIDE-II consensus advises immediate(clinical response),intermediate(clinical remission and biochemical normalisation)and long-term treatment(endoscopic healing,absence of disability and normalisation of health-related quality of life,as well as normal growth in children)endpoints in UC.However,achieving deeper levels of remission,such as histologic normalisation or healing of the gut barrier function,may further improve outcomes among UC patients.Generally,all medical therapy should seek to improve short-and long-term mortality and morbidity.Hence treatment endpoints should be chosen based on their ability to predict for improvement in short-and long-term mortality and morbidity.Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient.In addition,changing therapy that has achieved partial response may lead to worse outcomes,with failure to recapture response on treatment reversion.Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians,or may have strong opinions re certain therapies.Potential benefits and harms of therapies,incremental benefits of achieving deeper levels of remission,as well as uncertainties of the same,need to be discussed with individual patients,and a treatment endpoint agreed upon with the clinician.Future research should focus on quantifying the incremental b

关键词： Ulcerative colitis Treatment endpoints Endoscopic remission Histologic remission Biomarkers Gut barrier healing

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Two big orifices in the second duodenal portion:A case of an atypical double papilla

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 83-85页

作者： Salvatore Francesco Vadalàdi Prampero nikola Panic Marco Massidda Chiara Rocchi Pierluigi Maria Rinaldi Ana Malenkovic Milutin Bulajic Gastroenterology and GI Endoscopy Department Mater Olbia HospitalOlbia 07026Italy Digestive Endoscopy Unit University Clinic"Dr Dragisa Misovic-Dedinje"Belgrade 11000Serbia Radiology Department Mater Olbia HospitalOlbia 07026Italy

With the advent of endoscopic retrograde cholangiopancreatography(ERCP)in the early 1970s,anatomic anomalies of the Vaterian system were described endoscopically[1].Although the occurrence is rare,the common bile duct(CBD)and the pancreatic duct may fail to coalesce during embryologic development.This leads to double major papilla because both ducts open into the duodenum separately[1].In this way the cranial duct communicates with the CBD,while the caudal orifice communicates with the pancreatic duct[2].

关键词： orifice Vater atypical

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Role of copper chelating agents: between old applications and new perspectives in neuroscience

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Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella nikola Puvača Luca Piemontese Department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly Department of Precision and Regenerative Medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly Department of Engineering Management in Biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw nikola sp.igg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is unclear.Here,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of onset.The primary outcome was a shift in scores on the modified Rankin scale(mRS)at day 90.Secondary outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’markers.Data were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%CI.Results 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]min.Neuroimaging‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe stroke.Conclusions In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.WHAT IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those with acute stroke treated within 6hours of stroke

关键词： Glasgow nitrate random

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Structural changes of proteins in liver cirrhosis and consequential changes in their function

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World Journal of Gastroenterology 2022年第29期28卷 3780-3792页

作者： nikola Gligorijevic Simeon Minic Olgica Nedic Department of Metabolism University of Belgrade-Institute for the Application of Nuclear EnergyBelgrade 11080S Centre of Excellence for Molecular Food Sciences and Department of Biochemistry University of Belgrade-Faculty of ChemistryBelgrade 11000Serbia

The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose.Posttranslational modifications(PTMs)design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose.PTMs can change under pathological conditions,giving rise to aberrant or overmodified proteins.Undesired changes in the structure of proteins most often accompany undesired changes in their function,such as reduced activity or the appearance of new effects.Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control.Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation,nitration,glycosylation,acetylation,and ubiquitination.Some of them predominantly affect proteins that remain in liver cells,whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation.Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases,including cirrhosis.This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.

关键词： Liver cirrhosis Post-translational modifications Circulation Protein function Protein structure Chronic liver disease

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Dual biologic therapy with ocrelizumab for multiple sclerosis and vedolizumab for Crohn's disease:A case report and review of literature

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World Journal of Clinical Cases 2022年第8期10卷 2569-2576页

作者： Michael Au nikola Mitrev Rupert W Leong Viraj Kariyawasam Department of Gastroenterology and Hepatology Blacktown and Mt Druitt HospitalsWestern Sydney Local Health DistrictSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversityBlacktown 2148New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustralia Endoscopy Department and Inflammatory Bowel Disease Service Concord HospitalSydney 2137New South WalesAustralia Concord Clinical School University of SydneySydney 2137New South WalesAustralia Inflammatory Bowel Disease Service Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustria

BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated diseases.She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with diarrhoea.The CD diagnosis was confirmed radiologically,endoscopically,histologically,and biochemically.The patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on leukocytes.No adverse reactions were observed for the duration of treatment.The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated.CONCLUSION DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated diseases.Newer biologics,which have improved safety profiles and gut specificity,may provide promising avenues for treatment.However,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy profiles.Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary setting.Further research from controlled trials is needed to better understand the safety profile of DBT in CD.The immunopathological mechanisms underlying DBT also remain to be clarified.

关键词： Dual biologic therapy Combination Immunosuppression Safety Autoimmune Case report

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An Energy-Efficient Protocol for Internet of Things Based Wireless Sensor Networks

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Computers, Materials & Continua 2023年第5期75卷 2397-2412页

作者： Mohammed Mubarak Mustafa Ahmed Abelmonem Khalifa Korhan Cengiz nikola Ivkovic Department of Information Technology Sri Krishna College of Engineering&TechnologyCoimbatoreIndia Department of Networking and Security College of Information TechnologyUniversity of FujairahFujairahUAE Switching and Traffic Department National Telecommunication InstituteCairoEgypt Department of Computer Engineering Istinye UniversityZeytinburnuIstanbulTurkey Faculty of Organization and Informatics University of ZagrebVarazdinCroatia

The performance of Wireless Sensor Networks(WSNs)is an important fragment of the Internet of Things(IoT),where the current WSNbuilt IoT network’s sensor hubs are enticing due to their critical resources.By grouping hubs,a clustering convention offers a useful solution for ensuring energy-saving of hubs andHybridMedia Access Control(HMAC)during the course of the organization.Nevertheless,current grouping standards suffer from issues with the grouping structure that impacts the exhibition of these conventions negatively.In this investigation,we recommend an Improved Energy-Proficient Algorithm(IEPA)for HMAC throughout the lifetime of the WSN-based IoT.Three consecutive segments are suggested.For the covering of adjusted clusters,an ideal number of clusters is determined first.Then,fair static clusters are shaped,based on an updated calculation for fluffy cluster heads,to reduce and adapt the energy use of the sensor hubs.Cluster heads(CHs)are,ultimately,selected in optimal locations,with the pivot of the cluster heads working among cluster members.specifically,the proposed convention diminishes and balances the energy utilization of hubs by improving the grouping structure,where the IEPAis reasonable for systems that need a long time.The assessment results demonstrate that the IEPA performs better than existing conventions.

关键词： Energy consumption improved energy-proficient algorithm internet of things wireless sensor network

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Glial cells in intracerebral transplantation for Parkinson’s disease

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Neural Regeneration Research 2020年第7期15卷 1173-1178页

作者： nikola Tomov Institute of Anatomy University of Bern

In the last few decades,intracerebral transplantation has grown from a dubious neuroscientific topic to a plausible modality for treatment of neurological disorders.The possibility for cell replacement opens a new field of perspectives in the therapy of neurodegenerative disorders,ischemia,and neurotrauma,with the most lessons learned from intracerebral transplantation in Parkinson's disease.Multiple animal studies and a few small-scale clinical trials have proven the concept of intracerebral grafting,but still have to provide a uniform and highly efficient approach to the procedure,suitable for clinical application.The success of intracerebral transplantation is highly dependent on the integration of the grafted cells with the host brain.In this process,glial cells are clearly more than passive bystanders.They provide transplanted cells with mechanical support,trophics,mediate synapse formation,and participate in graft vascularization.At the same time,glial cells mediate scarring,graft rejection,and neuroinflammation,which can be detrimental.We can use this information to try to understand the mechanisms behind the glial reaction to intracerebral transplantation.Recognizing and utilizing glial reactivity can move translational research forward and provide an insight not only to post-transplantation events but also to mechanisms of neuronal death and degeneration.Knowledge about glial reactivity to transplanted cells could also be a key for optimization of transplantation protocols,which ultimately should contribute to greater patient benefit.

关键词： astroglia dopaminergic glial scarring microglia neuroinflammation Parkinson's disease transplantation

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