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Gastrointestinal and liver disease in patients with schizophrenia:A narrative review

World Journal of Gastroenterology 2022年第38期28卷 5515-5529页

作者： Rebecca K Grant William m Brindle mhairi C Donnelly Pauline M McConville Thomas G Stroud Lorenzo Bandieri John N Plevris The Centre for Liver and Digestive Disorders Royal Infirmary of EdinburghEdinburghEH164SAUnited Kingdom General Adult Psychiatry Royal Edinburgh HospitalEdinburghEH105HFUnited Kingdom

Schizophrenia is a severe mental illness which can have a devastating impact onan individual’s quality of life. Comorbidities are high amongst patients and lifeexpectancy is approximately 15 years less than the general population. Despite thewell-known increased mortality, little is known about the impact of gastrointestinaland liver disease on patients with schizophrenia. We aimed to reviewthe literature and to make recommendations regarding future care. Literaturesearches were performed on Pubmed to identify studies related to gastrointestinaland liver disease in patients with schizophrenia. High rates of chronic liverdisease were reported, with Non-Alcoholic Fatty Liver Disease being of particularconcern;antipsychotics and metabolic syndrome were contributing factors. Ratesof acute liver failure were low but have been associated with antipsychotic useand paracetamol overdose. Coeliac disease has historically been linked to schizophrenia;however, recent research suggests that a causal link is yet to be proven.Evidence is emerging regarding the relationships between schizophrenia andpeptic ulcer disease, inflammatory bowel disease and irritable bowel syndrome;clinical vigilance regarding these conditions should be high. Patients with schizophreniapoorly engage with bowel cancer screening programmes, leading to latediagnosis and increased mortality. Clozapine induced constipation is a significantissue for many patients and requires close monitoring. There is a significantburden of gastrointestinal and liver disease amongst patients with schizophrenia.Better levels of support from all members of the medical team are essential toensure that appropriate, timely care is provided.

关键词： Schizophrenia Gastrointestinal disease Liver disease mental health

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Three decades of unveiling the complex chemistry of C-nitroso species with computational chemistry

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Organic Chemistry Frontiers 2022年第1期9卷 223-264页

作者： pauline Bianchi Jean-Christophe m.monbaliu Center for Integrated Technology and Organic Synthesis MolSys Research UnitUniversity of LiègeB-4000 Liège(Sart Tilman)Belgium

C-Nitroso species are characterized by a unique nitrogen–oxygen combination located next to a carbon backbone,which confers them a unique ambiphilic and high reactivity towards nucleophilic,electrophilic but also radical species.Although this ambivalence can be seen as a strong asset for developing versatile synthetic aminohydroxylation and/or hydroxylamination processes mainly through nitroso Diels–Alder,nitroso ene,and nitrosoaldol reactions,it also contributes to complex optimization and rationalization arising from the many competitive pathways,that is,the occurrence of regioisomers and stereoisomers,as well as dimerization and tautomerization side-reactions.Complex reactivity profiles are usually seen by synthetic organic chemists as major hurdles to overcome,despite the armada of analytical and purification methods available to them,and hence to achieve selective and exploitable developments of such reactions.The rise of computational chemistry and resources has certainly changed their perspectives,since it provides a very different angle to gather insights on intrinsic properties,reactivity,and mechanisms.In silico chemistry also provides a robust alternative to time and resource-consuming synthetic work and can therefore contribute to alleviate wasteful preparations by guiding the chemist toward the best combination of reagents to achieve high selectivity and yield.The synergistic combination of synthetic organic chemistry and computational chemistry,within the specific context of the complex chemistry of C-nitroso species,is discussed in this work.This review aims at giving an overview of the molecular and chemical properties obtained through computational chemistry as an enabling support for the rationalization and optimization of reactions relying on ambiphilic C-nitroso species over the 3 last decades.It provides clear,concise,and illustrated guidelines for the synthetic chemist in search of inspiration through computations.

关键词： chemistry reactivity isomers

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：ognitive changes associated with ADT： a review of the iterature

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Asian Journal of Andrology 2012年第2期14卷 232-238页

作者： Rhoda J Jamadar mary J Winters pauline m maki Center for Cognitive medicine Department of Psychiatry university of Illinois at Chicago Chicago IL 60612 USA Department of Psychology University of Illinois at Chicago Chicago IL 60612 USA

The use of androgen deprivation therapy （ADT） has increased since the early 1990s after early detection efforts and greater use of the prostate-specific antigen （PSA） test. Although ADT is associated with favorable clinical outcomes, ADT has been associated with an increased risk for cardiovascular disease, increased serum cholesterol, triglycerides, insulin resistance, body mass index and fat body mass. Here we review findings from 11 clinical studies examining the effects of ADT on cognition as measured by standardized tests in cognitive domains such as verbal and spatial memory. most of these studies have important limitations, including small sample sizes, suboptimal control groups and baseline group differences in confounding factors. Despite these limitations, the best designed studies, those comparing patients on ADT to healthy controls, generally suggest that spatial memory might be especially sensitive to the effects of ADT. Critically, to date there is only one study involving random assignment of ADT versus close clinical observation. That study revealed a decrease in verbal memory with ADT, but was limited in sample size and did not include a measure of spatial memory. A recent observational study revealed no substantial evidence of cognitive impairment with ADT, even in the domain of verbal memory. Like the randomizedstudy, however, this large observational study lacked a measure of spatial memory. Overall, the studies with the best controls suggest a potential negative impact of ADT on spatial memory, and perhaps verbal memory, and a need for continued investigation of the impact of ADT on cognition, particularly in these two cognitive domains.

关键词： androgen deprivation therapy cognition prostate cancer

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Quality improvement in pediatric inflammatory bowel disease: moving forward to improve outcomes

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World Journal of Gastroenterology 2013年第38期19卷 6367-6374页

作者： pauline Quach Geoffrey C Nguyen Eric I Benchimol CHEO IBD Centre Division of GastroenterologyHepatology and NutritionChildren’s Hospital of Eastern OntarioOttawa K1H 8L1Canada Institute for Clinical Evaluative Sciences Ottawa K1Y 4E9Canada Zane Cohen Center for Digestive Research Division of GastroenterologyMount Sinai HospitalToronto M5T 3L9Canada Department of medicine University of TorontoToronto M5S 2J7Canada Departments of Pediatrics Epidemiology and Community MedicineUniversity of OttawaOttawa K1H 8M5Canada

In recent years,pediatric health care has embraced the concept of quality improvement to improve patient outcomes.As quality improvement efforts are implemented,network collaboration(where multiple centers and practices implement standardized programs)is a popular option.In a collaborative network,improvement in the conduct of structural,process and outcome quality measures can lead to improvements in overall health,and benchmarks can be used to assess and compare progress.In this review article,we provided an overview of the quality improvement movement and the role of quality indicators in this movement.We reviewed current quality improvement efforts in pediatric inflammatory bowel disease (IBD),as well as other pediatric chronic illnesses.We discussed the need to standardize the development of quality indicators used in quality improvement networks to assess medical care,and the validation techniques which can be used to ensure that process indicators result in improved outcomes of clinical significance.We aimed to assess current quality improvement efforts in pediatric IBD and other diseases,such as childhood asthma,childhood arthritis,and neonatal health.By doing so,we hope to learn from their successes and failures and to move the field forward for future improvements in the care provided to children with IBD.

关键词： Inflammatory bowel disease Colitis Ulcerative Crohn’s disease Child Adolescent Quality of health care Review

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美英知识产权纠纷中的定损评估评介

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电子知识产权 2015年第4期 72-76页

作者： pauline m. Booth Dr. michael :Salve

知识产权纠纷的损失评估可能会非常复杂。许多在法庭上辩称过、已裁定的案例中,一些突出的问题给我们提供了今后赔偿计算和案例所在司法辖区的认可解决方式的依据。文本总结了不同知识产权纠纷的种类及每种纠纷的损失赔偿金类型1。通过... 详细信息

知识产权纠纷的损失评估可能会非常复杂。许多在法庭上辩称过、已裁定的案例中,一些突出的问题给我们提供了今后赔偿计算和案例所在司法辖区的认可解决方式的依据。文本总结了不同知识产权纠纷的种类及每种纠纷的损失赔偿金类型1。通过美国和英国的重要案例,详细解释每种类型的赔偿金的计算方法,以及被告利润与合理的许可使用费这两种损失赔偿金的计算方法。

关键词：赔偿版税专利商标商业秘密

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知识产权纠纷中的定损专家应用和定损问题评介

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电子知识产权 2014年第6期 62-67页

作者： pauline m.Booth Dr.michael Salve 奥迈咨询顾问公司纽约办公室

介绍与知识产权纠纷相关的常见定损问题的基础性背景信息,并概述定损专家的角色、知识产权纠纷的类型以及相关的损失赔偿金的判定。此外,还探讨美国和英国法院以及国际仲裁法庭在对每个案例进行赔偿金分析时所需的证据的要求,并详细讨... 详细信息

介绍与知识产权纠纷相关的常见定损问题的基础性背景信息,并概述定损专家的角色、知识产权纠纷的类型以及相关的损失赔偿金的判定。此外,还探讨美国和英国法院以及国际仲裁法庭在对每个案例进行赔偿金分析时所需的证据的要求,并详细讨论与原告所提出之利润损失索赔相关的证据和分析。

关键词：知识产权纠纷定损专家评介应用背景信息国际仲裁赔偿金

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Anti program death-1/anti program death-ligand 1 in digestive cancers

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World Journal of Gastrointestinal Oncology 2015年第8期7卷 95-101页

作者： Eléonore de Guillebon pauline Roussille Eric Frouin David Tougeron medical Oncology Department Poitiers University Hospital Radiation Oncology Department Poitiers University Hospital Pathology Department Poitiers University Hospital David Tougeron Laboratory Inflammation Tissus Epithéliaux et Cytokines EA 4331 Poitiers University Gastroenterology Department Poitiers University Hospital

Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies(m Abs), called immune checkpoint inhibitors(ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. multiple anti-PD-1(nivolumab, pembrolizumab) and anti-PD-L1 m Abs(mPDL3280A, medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase Ⅱ will start soon. In metastatic colorectal cancer(CRC), a phase Ⅲ trial of mPDL3280 A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration(i.e., microsatellite instability). major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection ofpatients likely to benefit from ICIs.

关键词： Program death-1 Program death-ligand 1 Antibody Digestive cancer

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Juvenile ferric iron prevents microbiota dysbiosis and colitis in adult rodents

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World Journal of Gastroenterology 2012年第21期18卷 2619-2629页

作者： Chourouk Ettreiki Pascale Gadonna-Widehem Irène mangin mose Coёffier Carine Delayre-Orthez pauline m Anton Egeal Unit LaSalle Beauvais Polytechnic Institute60026 Beauvais France Biology Lab National Conservatory of Arts and Crafts75003 Paris France INSERm UmR 1073 School of Medicine Rouen University76183 Rouen France

AIm: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. mETHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (mPO) activity. Alteration of the microflora profile was estimated usingquantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria. RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 mPO U/mg proteinvs 2.47 ± 0.22 mPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of mPO activity (1.64 ± 0.14 mPO U/mg protein) in TNBS-induced colitis. moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of mPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quant

关键词：啮齿类动物成年大鼠三价铁结肠炎微生物少年硝基苯磺酸髓过氧化物酶

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Glycosylation engineering of therapeutic IgG antibodies： challenges for the safety, functionality and efficacy

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Protein & Cell 2018年第1期9卷 47-62页

作者： Yusuke mimura Toshihiko Katoh Radka Saldova Roisin O'Flaherty Tomonori Izumi Yuka mimura-Kimura Toshiaki Utsunomiya Yoichi mizukami Kenji Yamamoto Tsuneo matsumoto pauline m. Rudd Department of Clinical Research NHO Yamaguchi-Ube Medical Center 685 Higashi-Kiwa Ube 755-0241 Japan Laboratory of molecular Biology and Bioresponse Division of Integrated Life Science Graduate School of Biostudies KyotoUniversity Kitashirakawa Oiwake-Cho Sakyo-Ku Kyoto 606-8502 Japan NIBRT GlycoScience Group National Institute for Bioprocessing Research and Training Mount Merrion Blackrock Dublin 4Ireland Center for Regenerative medicine Yamaguchi University Graduate School of Medicine 1-1-1 Minami Kogushi Ube 755-8505 Japan Center for Gene Research Yamaguchi University 1-1-1 Minami-Kogushi Ube 755-8505 Japan Research Institute for Bioresources and Biotechnology Ishikawa Prefectural University 1-308 Suematsu Nonoichi Ishikawa 921-8836 Japan

Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex.type oligosaccharide attached to Asn297 of the Fc is essen- tial for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that gen- erate structural heterogeneity （glycoforms） exhibit unique biological activities. Hence, efficient and quan- titative glycan analysis techniques have been increas- ingly important for the development and quality control of therapeutic antibodies, and g｜ycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosy- lation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibili- ties for the design of novel antibody therapeutics. Fur- thermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosyn- thases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next- generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety,functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.

关键词： chemoenzymatic glycoengineering crysta structure endoglycosidase fucose glycosylation,intravenous immunoglobulin sialic acid transglycosylation,ultra performance liquid chromatography

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Adult meerkats modify close call rate in the presence of pups

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Current Zoology 2017年第3期63卷 349-355页

作者： megan T. WYmAN Pearl R. RIVERS Coline mULLER pauline TONI marta B. mANSER Department of Evolutionary Biology and Environmental Studies University of Zurich Winterthurerstrasse 190 Zurich CH 8057 Switzerland Kalahari meerkat Project Kuruman River Reserve P.O. Box 64 Van Zylsrus Northern Cape 8467 South Africa

In animals, signaling behavior is often context-dependent, with variation in the probability of emitting certain signals dependent on fitness advantages. Senders may adjust signaling rate depending on receiver identity, presence of audiences, or noise masking the signal, all of which can affect the benefits and costs of signal production. In the cooperative breeding meerkat , group members emit soft contact calls, termed as "close calls", while foraging in order to maintain group cohesion. Here, we investigated how the close calling rate during foraging was affected by the presence of pups, that produce continuous, noisy begging calls as they follow older group members. Adults decreased their overall close call rate substantially when pups were foraging with the group in comparison to periods when no pups were present. We suggest this decrease was likely due to a masking effect of the loud begging calls, which makes the close call function of maintaining group cohesion partly redundant as the centrally located begging calls can be used instead to maintain cohesion. There was some support that adults use close calls strategically to attract specific pups based on fitness advantages, that is, as the philopatric sex, females should call more than males and more to female pups than male pups. Dominant females called more than dominant males when a pup was in close proximity, while subordinates showed no sex-based differences. The sex of the nearest pup did not affect the calling rate of adults. The study shows that meerkats modify their close call production depending on benefits gained from calling and provides an example of the flexible use of one calling system in the presence of another, here contact calls versus begging calls, within the same species.

关键词：呼叫系统关闭修改成年信号速率性别差异狐凝聚力

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