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Functional dyspepsia:Are psychosocial factors of relevance?

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World Journal of gastroenterology 2006年第17期12卷 2701-2707页

作者： Sandra Barry timothy g dinan Department of Psychiatry and Alimentary Pharmacobiotic Centre University College Cork CorkIreland

The pathogenesis of Functional Dyspepsia （FD） remains unclear, appears diverse and is thus inadequately understood. Akin to other functional gastrointestinal disorders, research has demonstrated an association between this common diagnosis and psychosocial factors and psychiatric morbidity. Conceptualising the relevance of these factors within the syndrome of FD requires application of the biopsychosocial model of disease. Using this paradigm, dysregulation of the reciprocal communication between the brain and the gut is central to symptom generation, interpretation and exacerbation. Appreciation and understanding of the neurobiological correlates of various psychological states is also relevant. The view that psychosocial factors exert their influence in FD predominantly through motivation of health care seeking also persists. This appears too one-dimensional an assertion in light of the evidence available supporting a more intdnsic aetiological link. Evolving understanding of pathogenic mechanisms and the heterogeneous nature of the syndrome will facilitate effective management. Co-morbid psychiatric illness warrants treatment with conventional therapies. Acknowledging the relevance of psychosocial variables in FD, the degree of which is subject to vadation, has implications for assessment and management. Available evidence suggests psychological therapies may benefit FD patients particularly those with chronic symptoms. The rationale for use of psychotropic medications in FD is apparent but the evidence base to support the use of antidepressant pharmacotherapy is to date limited.

关键词： Functional dyspepsia Psychosocial factors Psychiatry Pathophysiology

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 *** pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been *** 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

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 *** In this retrospective study,623 participants with IBS were recruited from five specialty centers in germany,Sweden,the United States,the United Kingdom,and ***,anxiety,and somatization symptoms and sociodemographic characteristics were *** 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 *** also performed separate analyses for sex and IBS *** scores were calculated as the number of minor alleles of the SNPs *** impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx *** 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 *** potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant *** We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with *** 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

Bulking Up the Bay-Position Substituents Enables Enhanced Selectivity of C_(s)‑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 ***,selective,and controllable routes to boron subphthalocyanine−subnaphthalocyanine hybrids,Bsub(Pc_(3‑p)-Nc_(p))s,are desirable for this purpose yet synthetically challenging due to random mixtures of C_(s-),C_(3v-),and,in some cases,C_(1)-symmetric compounds that form during traditional statistical mixed ***,we addressed this issue by developing a sterically driven mixed cyclotrimerization with enhanced selectivity for the targeted C_(s)-symmetric hybrid and complete suppression of sterically crowded macrocyclic *** process,coupled with a rationally designed precursor bearing bulky phenyl substituents,enabled the synthesis and characterization of bay-position phenylated Ph_(2)-(R_(p))_(8)Bsub(Pc_(2)-Nc_(1))hybrids with halogens(Rp=Cl or F)in their peripheral isoindole *** selectivity ranged between 59 and 72%with remarkable yields,significantly higher than that of conventional mixed *** findings were augmented by theoretical calculations on precursor Lewis basicity as guiding principles into hybrid macrocycle ***,the incorporation of unfused phenyl groups and halogen atoms into the hybrid framework resulted in fine-tuned optical,structural,electronic,and electrochemical *** straightforward approach achieved improved selectivity and controlled narrowing of the product distribution,affording the efficient synthesis of structurally sophisticated Bsub(Pc_(2)-Nc_(1))*** 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 EnvironmentMassey UniversityPalmerston North 4442New Zealand Department of Animal Science and Nutrition Faculty of Veterinary MedicineChattogram Veterinary and Animal Sciences UniversityKhulshiChattogram 4225Bangladesh Nutrition and Care Animal NutritionEvonik(SEA)Pte.Ltd609927 Singapore Complete Feed Solutions Howick 2145AucklandNew Zealand

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 *** 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 *** 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),*** apparent digestibility coefficients were standardized using age-specific basal endogenous AA *** 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 *** SIDC of some individual AA(Arg,Thr,Trp,Cys,Pro)were affected(Pge SIDC of IAA,DAA and TAA were influenced(quadratic;Pge SIDC of DAA and TAA were higher from d 7 to 14,declined at d 21,and then increased beyond d *** average SIDC of IAA was low between d 7 and 28 and increased *** SIDC of individual AA were affected(linear or quadratic;Pgnitudes by *** age influence on the SIDC AA was variable,depending on the protein source and *** 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

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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 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 ***,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 *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** 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’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 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]***‘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 *** 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 *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(gTN)was associat-ed with less death and dependency in those w

关键词： glasgow nitrate random

The paternal epigenome and embryogenesis： poising mechanisms for development

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Asian Journal of Andrology 2011年第1期13卷 76-80页

作者： timothy g Jenkins Douglas T Carrell Andrology and IVF Laboratories Department of Surgery University of Utah Salt Lake City UT 84108 USA Department of Obstetrics and gynecology University of Utah School of Medicine Salt Lake City UT 84108 USA Department of Physiology University of Utah School of Medicine Salt Lake City UT 84108 USA

The scope of paternal contributions during early embryonic development has long been considered limited. Dramatic changes in chromatin structure throughout spermatogenesis have been thought to leave the sperm void of complex layers of epigenetic regulation over the DNA blueprint, thus leaving the balance of that regulation to the oocyte. However, recent work in the fields of epigenetics and male factor infertility has placed this long-held, and now controversial dogma, in a new light. Elegant studies investigating chromatin and epigenetic modifications in the developing sperm cell have provided new insights that may establish a more critical role for the paternal epigenome in the developing embryo. DNA methylation, histone tail modifications, targeted histone retention and protamine incorporation into the chromatin have great influence in the developing sperm cell. Perturbations in the establishment and/or maintenance of any of these epigenetic marks have been demonstrated to affect fertility status, ranging in severity from mild to catastrophic. Sperm require this myriad of chromatin structural changes not only to serve a protective role to DNA throughout spermatogenesis and future delivery to the egg, but also, it appears, to contribute to the developmental program of the future embryo. This review will focus on our current understanding of the epigenetics of sperm. We will discuss sperm-specific chromatin modifications that result in genes essential to development being poised for activation early in embryonic development, the disruption of which may result in reduced fecundity.

关键词： chromatin DNA methylation embryogenesis epigenetics histone modification male infertility

graph-theoretic algorithms for cyber-physical vulnerability analysis of power grid with incomplete information

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Journal of Modern Power Systems and Clean Energy 2018年第5期6卷 887-899页

作者： Anurag K.SRIVASTAVA timothy A.ERNSTER Ren LIU Vignesh g.KRISHNAN Department of Electrical Engineering and Computer Science Washington State University U.S. Army Corps of Engineers Dominion Power

A key focus recently has been on assessing therisk of a coordinated cyber-physical attack and minimizing the impact of a successful attack. Most of the cyberattackers will have limited system information and conventional power grid N-1 security analysis cannot be extended to assess the risk. Centrality measures are widely used in the network science and an attacker with incomplete information can use it to identify power system vulnerabilities by defining the system as a complex network but without real-time system measurements. This paper presents a graph theory based centrality indices for vulnerability assessment of the power system due to various bus and branch contingencies using limited system information and provides a preliminary defense mechanism to prevent such an attack. Proposed work answers the fundamental question of possible attack scenarios by balancing risk(limited information with low risk to get caught orhigh risk attack to access more system information) and impact(identifying contingencies with maximal impact on system operation). Statistical comparisons are made between the graph theory measures compared to the corresponding DC power flow based N-X linear sensitivity measures. A unified N-X centrality based performance index is proposed and validated against the AC power flow based performance index by doing the real-time simulations of an N-3 attack scenario. Defensive mechanisms using topology-based performance indices are also presented.

关键词： Cyber-physical security graph theory Transmission system Contingency Defense mechanism Incomplete information

Comparison of Results of Recent Seismic Profiles with Tectonic Models of the North China Craton

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Journal of Earth Science 2011年第2期22卷 250-259页

作者： timothy M Kusky State Key Laboratory of geological Processes and Mineral Resources Three Gorges Research Center for Geo-hazardMinistry of EducationChina University of Geosciences

The geometry and timing of amalgamation of the North China craton（NCC） have been controversial,with three main models with significantly different interpretations of regional structure,geochronology,and geological *** model of Zhao g C et *** that the eastern and western blocks of the NCC formed separately in the Archean,and an active margin was developed on the eastern block between 2.5 and 1.85 ga,when the two blocks collided above an east dipping subduc-tion *** model of Kusky et *** that the eastern block rifted from an unknown larger continent at circa 2.7 ga,and experienced a collision with an arc（perhaps attached to the western block） above a west-dipping subduction zone at 2.5 ga,and the 1.85 ga metamorphism is related to a collision along the northern margin of the craton when the NCC joined the Columbia *** model of Faure et *** two collisions in the central orogenic belt,at 2.1 and 1.88 *** seismic results support both the models of Kusky et *** Faure et al.,showing that subduction be-neath the central orogenic belt（COB） was west-directed,and that there is a second,west-dipping pa-leosubduction zone located to the east of the COB dipping beneath the western block（Ordos craton）.The boundaries identified through geophysics do not correlate with the boundaries of the Trans-North China orogen suggested in the Zhao et ***,and the subduction polarity is opposite that predicted by that *** seismic profiles are consistent with an Archean collision above a west-dipping sub-duction zone beneath the COB predicted by the models of Kusky et al.,and the second west-dipping subduction zone is consistent with the two events suggested in the Faure et ***.

关键词： North China craton Archean tectonics geophysics.