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Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

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World Journal of gastroenterology 2014年第39期20卷 14105-14125页

作者： Paul J Kennedy John F Cryan timothy g dinan gerard Clarke 1.15 Biosciences Institute Department of Psychiatry Alimentary Pharmabiotic Centre University College Cork Cork Ireland Department of Anatomy and Neuroscience Alimentary Pharmabiotic CentreUniversity College CorkCork Ireland

Irritable bowel syndrome(IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions.

关键词： Irritable bowel syndrome Microbiome Anxi-ety Trypt

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study

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World Journal of gastroenterology 2022年第21期28卷 2334-2349页

作者： Sabrina Berens Yuanjun Dong Nikola Fritz Jutta Walstab Mauro D'Amato Tenghao Zheng Verena Wahl Felix Boekstegers Justo Lorenzo Bermejo Cristina Martinez Stefanie Schmitteckert Egbert Clevers Felicitas Engel Annika gauss Wolfgang Herzog Robin Spiller Miriam goebel-Stengel Hubert Mönnikes Viola Andresen Frieling Thomas Jutta Keller Christian Pehl Christoph Stein-Thöringer gerard Clarke timothy g dinan Eamonn M Quigley gregory Sayuk Magnus Simrén Jonas Tesarz gudrun Rappold Lukas van Oudenhove Rainer Schaefert Beate Niesler Department of general Internal Medicine and Psychosomatics University Hospital HeidelbergHeidelberg 69120Germany Department of Human Molecular genetics Institute of Human GeneticsUniversity of HeidelbergHeidelberg 69120Germany Department of general Internal Medicine and Psychosomatics Internal Medicine IIUniversity Hospital HeidelbergHeidelberg 69120Germany Department of Human Molecular genetics University of HeidelbergHeidelberg 69120Germany gastrointestinal genetics Lab CIC bioGUNE-BRTADerio 48160Spain IKERBASQUE Basque Foundation for ScienceBilbao 48001Spain Unit of Clinical Epidemiology Department of Medicine SolnaKarolinska InstitutetStockholm 17177Sweden Institute of Medical Biometry and Informatics Heidelberg UniversityHeidelberg 69120Germany Lleida Institute for Biomedical Research Dr.PifarréFoundation(IRBLleida) Av.Alcalde Rovira RoureLleida 25198Spain Department of Clinical and Experimental Medicine Translational Research Center for Gastrointestinal DisordersKU LeuvenLeuven 3000Belgium Department of gastroenterology Infectious Diseases and IntoxicationsUniversity of HeidelbergHeidelberg 69120Germany Department of general Internal Medicine and Psychosomatics Heidelberg UniversityHeidelberg 69120Germany Nottingham Digestive Diseases Centre University of NottinghamNottingham NG72QLUnited Kingdom Helios Klinikum Rottweil Rottweil 78628Germany Department of Medicine Institute of Neurogastroenterology(H.M.)Martin-Luther-HospitalBelin 14193Germany Israelitisches Krankenhaus in Hamburg Hamburg 22297Germany Internal Medicine II Helios Klinikum KrefeldKrefeld 47805Germany Israelitisches Krankenhaus Hamburg Hamburg 22297Ghana Krankenhaus Vilsbiburg Vilsbiburg 84137Germany Division of Microbiome and Cancer German Cancer Research Center(DKFZ)Heidelberg 69120Germany Department of Psychiatry and Neurobehavioral Science University College CorkCork T23Ireland Medicine in Digestive Disorders Department of MedicineLynda K.and David M.Underwood Center for Digestive DisordersHou

BACKgROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76g>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

关键词： Irritable bowel syndrome 5-HT3 receptor subunit gene polymorphisms Single-nucleotide polymorphism score Depression Anxiety Somatization

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration Research 2025年第2期20卷 481-482页

作者： Khaled Alok timothy g.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA Translational Brain Research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological damage.While pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been established.The objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

Bulking Up the Bay-Position Substituents Enables Enhanced Selectivity of Cs‑Symmetric Boron Subphthalocyanine−Subnaphthalocyanine Hybrids

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Precision Chemistry 2024年第4期2卷 161-181页

作者： Nina F.Farac Alan J.Lough timothy P.Bender Department of Chemical Engineering and Applied Chemistry University of TorontoTorontoOntario M5S 3E5Canada Department of Chemistry University of TorontoTorontoOntario M5S 3H6Canada Department of Materials Science and Engineering University of TorontoTorontoOntario M5S 3E4Canada Department of Mechanical and Industrial Engineering University of TorontoTorontoOntario M5S 3G8Canada

The precise synthesis of subporphyrinoid hybrids withπ-expanded topologies and unique material properties plays a promising role in the design of functional macrocycles.Easy,selective,and controllable routes to boron subphthalocyanine−subnaphthalocyanine hybrids,Bsub(Pc_(3‑p)-Ncp)s,are desirable for this purpose yet synthetically challenging due to random mixtures of Cs-,C3v-,and,in some cases,C1-symmetric compounds that form during traditional statistical mixed cyclotrimerizations.Herein,we addressed this issue by developing a sterically driven mixed cyclotrimerization with enhanced selectivity for the targeted Cs-symmetric hybrid and complete suppression of sterically crowded macrocyclic byproducts.This process,coupled with a rationally designed precursor bearing bulky phenyl substituents,enabled the synthesis and characterization of bay-position phenylated Ph2-(Rp)8Bsub(Pc_(2)-Nc_(1))hybrids with halogens(Rp=Cl or F)in their peripheral isoindole rings.Reaction selectivity ranged between 59 and 72%with remarkable yields,significantly higher than that of conventional mixed cyclotrimerizations.These findings were augmented by theoretical calculations on precursor Lewis basicity as guiding principles into hybrid macrocycle formation.Additionally,the incorporation of unfused phenyl groups and halogen atoms into the hybrid framework resulted in fine-tuned optical,structural,electronic,and electrochemical properties.This straightforward approach achieved improved selectivity and controlled narrowing of the product distribution,affording the efficient synthesis of structurally sophisticated Bsub(Pc_(2)-Nc_(1))hybrids.This then expands the library of 3-dimensionalπ-extended macrocycles for use in a range of applications,such as in optoelectronic devices with precisely tailored optical properties.

关键词： subphthalocyanine hybrids low-symmetry aromatic macrocycle selective cyclotrimerization sterically driven chemistry broad absorption material properties

Effect of age on the standardized ileal amino acid digestibility of soybean meal and canola meal in broilers

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Animal Nutrition 2024年第1期16卷 11-22页

作者： Mukti Barua M.Reza Abdollahi Faegheh Zaefarian timothy J.Wester Channarayapatna K.girish Peter V.Chrystal Velmurugu Ravindran Monogastric Research Center School of Agriculture and Environment Massey University Department of Animal Science and Nutrition Faculty of Veterinary Medicine Chattogram Veterinary and Animal Sciences University Nutrition and Care Animal NutritionEvonik (SEA) Pte. Ltd Complete Feed Solutions

Standardized ileal digestibility coefficients (SIDC) of nitrogen (N) and amino acids (AA) in two protein sources (soybean meal [SBM] and canola meal [CM]) were investigated at six broiler ages (d 7, 14, 21, 28, 35, and 42). Two assay diets were formulated to contain either SBM (413 g/kg) or CM (553 g/kg) as the sole dietary AA source. Titanium dioxide (5 g/kg) was added as an indigestible marker. A total of 696 male broilers at 1 d old were allotted to 12 replicate cages per age group. Each assay diet was offered to birds for 4 d prior to the ileal digesta collection on d 7 (14 birds/cage), 14 (12 birds/cage), 21 (10 birds/cage), 28 (8 birds/cage), 35 (8 birds/cage) and 42 (6 birds/cage), respectively. The apparent digestibility coefficients were standardized using age-specific basal endogenous AA flows. In the SBM group, though the SIDC of N tended to be influenced (quadratic; P=0.075) by age, no linear or quadratic response of age effect was observed on the average SIDC of indispensable (IAA) and total AA (TAA). An age effect (quadratic; Pge SIDC of dispensable AA (DAA) in SBM with the highest value recorded at d 7, followed by a decrease from d 14 to 28, which increased beyond d 35. The SIDC of some individual AA (Arg, Thr, Trp, Cys, Pro) were affected (Pge. In the CM, the SIDC of N, average SIDC of IAA, DAA and TAA were influenced (quadratic; Pge. The SIDC of N and average SIDC of DAA and TAA were higher from d 7 to 14, declined at d 21, and then increased beyond d 28. The average SIDC of IAA was low between d 7 and 28 and increased thereafter. The SIDC of individual AA were affected (linear or quadratic; Pgnitudes by age. The age influence on the SIDC AA was variable, depending on the protein source and AA. The results demonstrate that age-specific SIDC AA data might need consideration in broiler feed formulations.

关键词： Age Amino acid Broiler Digestibility Protein source

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 Sprigg 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

Evaluation of a Wireless Solar Powered Personal Weather Station

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Agricultural Sciences 2024年第1期15卷 36-53页

作者： Robert J. Lascano timothy S. goebel Dennis C. gitz III John E. Stout Cropping Systems Research Laboratory Wind Erosion and Water Conservation Research Unit USDA-ARS Lubbock TX USA

We are evaluating dryland cotton production in Martin County, Texas, measuring cotton lint yield per unit of rainfall. Our goal is to collect rainfall data per 250 - 400 ha. Upon selection of a rainfall gauge, we realized that the cost of using, for example, a tipping bucket-type rain gauge would be too expensive and thus searched for an alternative method. We selected an all-in-one commercially available weather station;hereafter, referred to as a Personal Weather Station (PWS) that is both wireless and solar powered. Our objective was to evaluate average measurements of rainfall obtained with the PWS and to compare these to measurements obtained with an automatic weather station (AWS). For this purpose, we installed four PWS deployed within 20 m of the Plant Stress and Water Conservation Meteorological Tower that was used as our AWS, located at USDA-ARS Cropping Systems Research Laboratory, Lubbock, TX. In addition, we measured and compared hourly average values of short-wave irradiance (Rg), air temperature (Tair) and relative humidity (RH), and wind speed (WS), and calculated values of dewpoint temperature (Tdew). This comparison was done over a 242-day period (1 October 2022-31 May 2023) and results indicated that there was no statistical difference in measurements of rainfall between the PWS and AWS. Hourly average values of Rg measured with the PWS and AWS agreed on clear days, but PWS measurements were higher on cloudy days. There was no statistical difference between PWS and AWS hourly average measurements of Tair, RH, and calculated Tdew. Hourly average measurements of Rg and WS were more variable. We concluded that the PWS we selected will provide adequate values of rainfall and other weather variables to meet our goal of evaluating dryland cotton lint yield per unit rainfall.

关键词： Automation Sensors Citizen Weather Station Mesonet Rainfall Weather Variables

Comparative orotomy of the Archean Superior and Phanerozoic Altaid orogenic systems

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National Science Review 2023年第2期10卷 20-48页

作者： timothy M.Kusky A.M.Celal ?eng?r Center for global Tectonics School of Earth Sciences and State Key Laboratory for Geological Processes and Mineral ResourcesChina University of Geosciences Badong National Observatory and Research Station for geohazards Ministry of Education China University of Geosciences Department of geological Engineering Middle East Technical University Eurasia Institute of Earth Sciences Istanbul Technical University Department of geology Faculty of Mines Istanbul Technical University

We compare and contrast the materials and mechanisms of continental crustal growth in the largest preserved regions of Phanerozoic and Archean juvenile additions to the crust,to test for similarities or differences in the formation of continents through time.We accomplish this through a comparison of map patterns,lithological contents,and structural and metamorphic evolution of the Phanerozoic Altaid orogenic system of Asia,with the Archean Superior Province of the North American Craton,using a method termed comparative orotomy.Both orogenic systems consist of collages of curvilinear belts of eroded arcs,some older continental slivers,and vast tracts of former subduction/accretionary complexes.These contain numerous shreds of portions of the ophiolite suite,slivers of island and continental arcs,and accreted oceanic plateau,all intruded by multiple magmatic suites during or between multiple deformation events,then sliced by large transcurrent fault systems and bent into large oroclinal structures.We make this comparison because the Superior Province is a typical Archean craton that was later,in the P aleoproterozoic,incorporated into the larger North American Craton,and has occupied a central position in several super continents(e.g.Kenorland and Nuna,which then formed the core of Columbia,Rodinia,Laurentia and Pangea) during its longevity.Since it is the largest single fragment of Archean continental cratonic lithosphere preserved on Earth,the Superior Province is widely regarded as a testing ground for how Earth’s continental crust was formed.Likewise,the Altaids encompass the largest region of crustal growth for the Phanerozoic.Our comparison with the Altaids is needed,as in recent years many myths about how the planet may have responded to higher heat production and flow in the Archean have emerged,because of trends in the science where regional geology is ignored in favor of numerical models,isotopic proxies for assumed models of chemical behavior for crust-forming or tectonic processes,or comparisons with o

关键词： Altaids superior province ophiolite subduction strike-slip

Reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients

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World Journal of Transplantation 2022年第6期12卷 120-130页

作者： Penelope Hey Rudolf Hoermann Paul gow timothy P Hanrahan Adam g Testro Ross Apostolov Marie Sinclair Liver Transplant Unit Austin HealthHeidelberg 3084Australia Department of Medicine University of MelbourneMelbourne 3052Australia

BACKgROUND Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation days.Upper limb lean mass(LM)measured by dual-energy X-ray absorptiometry(DEXA)was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for transplantation.AIM To investigate the use of DEXA LM in predicting gender-stratified early posttransplant outcomes.METHODS Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were included.Endpoints included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACR)and intensive care and total hospital length of stay.RESULTS Four hundred and sixty-nine patients met inclusion criteria of which 338 were male(72%).Median age was 55.0 years(interquartile range 47.4,59.7)and model for end-stage liver disease(MELD)score 16.Median time from assessment to transplantation was 7 mo(3.5,12).Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant(hazard ratio=0.42;95%confidence interval:0.20-0.89;P=0.024)in males only.There was a negative correlation between upper limb LM and intensive care(τb=-0.090,P=0.015)and total hospital length of stay(τb=-0.10,P=0.0078)in men.In women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of stay.Body composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either gender.There were no significant predictors of early ACR.CONCLUSION Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with cirrhosis.DEXA upper limb LM provides a novel measure of muscle wasting that has prognostic value in this cohort.The lack of association in women requires further investigation.

关键词： Dual-energy X-ray absorptiometry Sarcopenia Body composition Liver transplantation Survival