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Involvement of insulin receptor substrates in cognitive impairment and Alzheimer’s disease

Neural Regeneration Research 2019年第8期14卷 1330-1334页

作者： Daisuke Tanokashira Wataru Fukuokaya Akiko Taguchi department of Integrative Aging Neuroscience National Center for Geriatrics and Gerontology Obu Aichi Japan division of Neurology Endocrinology and Metabolism Faculty of Medicine University of Miyazaki Miyazaki Japan

Type 2 diabetes一associated with impaired insulin/insulin-like growth factor-1 (IGF1) signaling (IIS)一is a risk factor for cognitive impairment and dementia including Alzheimer's disease (AD). The insulin receptor substrate (IRS) proteins are major components of IIS, which transmit upstream signals via the insulin receptor and/or IGF1 receptor to multiple intracellular signaling pathways, including AKT/protein kinase B and extracellular-signal-regulated kinase cascades. Of the four IRS proteins in mammals, IRS1 and IRS2 play key roles in regulating growth and survival, metabolism, and aging. Meanwhile, the roles of IRS1 and IRS2 in the central nervous system with respect to cognitive abilities remain to be clarified. In contrast to IRS2 in peripheral tissues, inactivation of neural IRS2 exerts beneficial effects, resulting in the reduction of amyloid p accumulation and premature mortality in AD mouse models. On the other hand, the increased phosphorylation of IRS 1 at several serine sites is observed in the brains from patients with AD and animal models of AD or cognitive impairment induced by type 2 diabetes. However, these serine sites are also activated in a mouse model of type 2 diabetes, in which the diabetes drug metformin improves memory impairment. Because IRS1 and IRS2 signaling pathways are regulated through complex mechanisms including positive and negative feedback loops, whether the elevated phosphorylation of IRS1 at specific serine sites found in AD brains is a primary response to cognitive dysfunction remains unknown. Here, we examine the associations between IRS 1 /1 RS2-mediated signaling in the central nervous system and cognitive decline.

关键词： type 2 diabetes insulin/insulin^like growth factor-1 insulin receptor substrate Alzheimer's disease aging serine phosphorylation metformin neuroprotective effects high-fat-diet

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Medical decision making for older adults： an international perspective comparing the United States and India

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Journal of Geriatric Cardiology 2015年第4期12卷 329-334页

作者： Ankur Kalra Daniel E Forman Sarah J Goodlin division of lnterventional Cardiology Beth lsrael Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA division of Cardiology Department of Medicine Kalra Hospital SRCNC Pvt. Ltd. New Delhi India Section of Geriatric Cardiology University of Pittsburgh Medical Center Pittsburgh PA USA geriatrics Research Education and Clinicai Center VA Pittsburgh Healthcare System Pittsburgh PA USA department of medicine-geriatrics Oregon Health & Sciences University and Veterans Affairs Portland Health Care System Portland Oregon USA

There has been a significant decline in cardiovascular morbidity and mortality amidst pervasive advances in care, including percutane- ous revascularization, mechanical circulatory support, and transcatheter valvular therapies. While advancing therapies may add significant longevity, they also bring about new end-of-life decision-making challenges for patients and their families who also must weigh the advan- tages of reduced mortality to the possibility of longer lives consisting of high morbidity, frailty, pain, and poor quality of living. Advance care entails options of withholding or withdrawing therapies, and has become a familiar part of cardiovascular care for older patients in Western countries. However, as advanced cardiovascular practices extend to developing countries, the interrelated concept of advance care is rarely straight forward as it is affected by local cultural traditions and mores, and can lead to very different inferences and use. This paper discusses the concepts of advance care planning, surrogate decision-making, orders for resuscitation and futility in patients with cardiac dis- ease with comparisons of West to East, focusing particularly on the United States versus India.

关键词： Advance care planning Advance directive End-of-life India Surrogate decision-making

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Foundations of medical decision-making for older adults with cardiovascular disease

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Journal of Geriatric Cardiology 2015年第4期12卷 335-339页

作者： Hannah I Lipman Ankur Kalra James N Kirkpatrick department of medicine Divisions of Geriatrics and Cardiology Montefiore Medical Center of the Albert Einstein College of Medicine Bronx N~ USA Minneapolis Heart Institute at Abbott Northwestern Hospital Department of Medicine Division of Cardiology Hennepin County Medical Center Minneapo- lis MN USA Cardiovascular division Department of Medicine University of Pennsylvania' Department of Medical Ethics and Health Policy University of Pennsylvania Philadelphia PA USA

In order to help older adults with cardiovascular disease navigate complex decisions, clinicians must know tenets of medical ethics and have good communication skills. The elements of decision making capacity and informed consent are reviewed, using relevant clinical ex- amples to illustrate the basic concepts. The shared decision making model, by which clinician and patient work together to determine the plan of care, is described. Useful communication techniques to implement shared decision making are suggested.

关键词： Cardiovascular disease Medical decision-making Older adults

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Liver transplantation in the era of non-alcoholic fatty liver disease/metabolic(dysfunction)associated fatty liver disease:the dilemma of the steatotic liver graft on transplantation and recipient survival

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Hepatobiliary Surgery and Nutrition 2022年第3期11卷 425-429页

作者： Seren M.Gedallovich Daniela P.Ladner Lisa B.VanWagner division of palliative medicine Department of MedicineUniversity of California San FranciscoSan FranciscoCAUSA division of Organ Transplantation Department of SurgeryNorthwestern University Feinberg School of MedicineChicagoILUSA division of Gastroenterology&Hepatology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA division of Epidemiology Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA

Liver transplantation remains the only curative therapy for end-stage liver disease and there is a well-established shortage of transplantable deceased donor organs to meet the growing demand of waitlisted *** liver grafts represent the most common type of so-called extended criteria donor(ECD)grafts aimed at ameliorating this ***,steatotic grafts are associated with increased post-transplant complications and graft failure(1).Hepatic graft steatosis is strongly correlated with the high prevalence of non-alcoholic fatty liver disease(NAFLD)and metabolic(dysfunction)associated fatty liver disease(MAFLD)in the general *** and MAFLD are related,but not equivalent,liver disorders that are linked with obesity and diabetes(2).Global prevalence of NAFLD is estimated at~25%and rising(3).Models predict that NAFLD prevalence will increase by 21%to affect 100.9 million persons worldwide by 2030(4).As more donors have NAFLD,the steatotic liver graft will continue to be a challenge for liver ***,promising efforts(e.g.,organ pump with defatting agents)are under way,aimed at expanding the donor pool in the coming ***,we briefly summarize approaches for assessment of hepatic steatosis,describe recipient outcomes associated with the use of steatotic liver grafts,and highlight strategies that may be used to mitigate risk considering the ongoing NAFLD/MAFLD epidemic.

关键词： organs graft donor

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Cryo-EM advances in RNA structure determination

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Signal Transduction and Targeted Therapy 2022年第3期7卷 601-606页

作者： Haiyun Ma Xinyu Jia Kaiming Zhang Zhaoming Su The State Key Laboratory of Biotherapy Department of Geriatrics and National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610044China MOE Key Laboratory for Cellular Dynamics and division of Life Sciences and medicine University of Science and Technology of ChinaHefei 230027China

Cryo-electron microscopy(cryo-EM)has emerged as an unprecedented tool to resolve protein structures at atomic *** insights of biological samples not accessible by conventional X-ray crystallography and NMR can be explored with cryo-EM because measurements are carried out under near-native crystal-free conditions,and large protein complexes with conformational and compositional heterogeneity are readily *** has remained underexplored in cryo-EM,despite its essential role in various biological *** review highlights current challenges and recent progress in using cryo-EM singleparticle analysis to determine protein-free RNA structures,enabled by improvement in sample preparation and integration of multiple structural and biochemical methods.

关键词： structure determination insight

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Low DHEAS levels are associated with depressive symptoms in elderly Chinese men： results from a large study

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Asian Journal of Andrology 2011年第6期13卷 898-902页

作者： Samuel YS Wong Jason C Leung Timothy Kwok Claes Ohlsson Liesbeth Vandenput Ping C Leung Jean Woo School of Public Health and Primary care School of Public Health The Chinese University of Hong Kong Hong Kong China jockey Club Centre for Osteoporosis care and Control The Chinese University of Hong Kong Hong Kong China department of medicine and Therapeutics The Chinese University of Hong Kong Hong Kong China Center for Bone Research Department of Internal Medicine University of Gothenburg Gothenburg SE-413 45 Sweden division of geriatrics Department of Medicine and Therapeutics The Chinese University of Hong Kong Hong Kong China

This study investigated the association between depressive symptoms in elderly Chinese men and the total testosterone, dehydroepiandrosterone （DHEA）, DHEA sulphate （DHEAS）, oestradiol and sex hormone-binding globulin （SHBG） levels, and the free androgen index. Cross-sectional data from 1147 community-dwelling elderly men, aged 65 and older, were used. Depressive symptoms were measured using the Chinese Geriatric Depression Scale （GDS）. Total testosterone, free testosterone, DHEA, DHEAS, total oestradiol, the free androgen index and SHBG levels were assessed. DHEA was significantly associated with GDS score, and there was a trend towards DHEAS association, but this was not significant （p=-0. 110, P=0.015; p=-0.074, P=0.055）. However, no association was seen between depressive symptoms and total testosterone levels, free testosterone levels, oestradiol levels or SHBG levels. In terms of the presence of clinically relevant depressive symptoms, there were no statistically significant differences between patients in the lowest quartile of sex steroid hormone levels and those in other quartiles of sex steroid hormone levels. Similarly to Western studies, our study shows that DHEA and DHEAS levels are associated with depressive symptoms.

关键词： Chinese dehydroepiandrosterone depression elderly men testosterone

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Structured magnetic resonance imaging and endoanal ultrasound anal fistulas reporting template(SMART):An interdisciplinary Delphi consensus

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World Journal of Gastrointestinal Surgery 2024年第10期16卷 3288-3300页

作者： Iwona Sudoł-Szopińska Pankaj Garg Anders Mellgren Antonino Spinelli Stephanie Breukink Francesca Iacobellis Małgorzata Kołodziejczak Przemysław Ciesielski Christian Jenssen SMART Collaborative Group Giulio Aniello Santoro department of Radiology National Institute of GeriatricsRheumatology and RehabilitationWarsaw 02-637Poland department of Colorectal Surgery Garg Fistula Research InstitutePanchkula 134113HaryanaIndia department of Surgical Oncology King Faisal Specialist Hospital&Research CenterRiyadh 11211Saudi Arabia department of Biomedical Sciences Humanitas UniversityPieve Emanuele-MilanItaly IRCCS Humanitas Research Hospital Rozzano-MilanItaly department of Surgery Maastricht and NUTRIM Institute of Nutrition and Translational Research in Metabolism GROW-Research Institute for Oncology and Reproductionthe Netherlands department of General and Emergency Radiology A.Cardarelli HospitalNaples 80131CampaniaItaly Warsaw Proctology Center St.Elizabeth HospitalWarsaw 02-616Poland department of Internal medicine Hospital Märkisch OderlandStrausberg 15344BrandenburgGermany Brandenburg Institute for Clinical Ultrasound Neuruppin 16186BrandenburgGermany Third Referral Pelvic Floor Center Division of Surgery 2AULSS n.2 Marca TrevigianaDISCOG University of PaduaTrevisoItaly 不详

BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical *** a con-sequence,the quality and completeness of the report are highly dependent on the training and experience of the *** To develop a structured MRI and EAUS template(SMART)reporting the minimum dataset of information for the treatment of anal *** This modified Delphi survey based on the RAND-UCLA appropriateness for consensus-building was conducted between May and August *** hundred and fifty-one articles selected from a systematic review of the lite-rature formed the database to generate the evidence-based statements for the Delphi *** questions were anonymously voted by an interdisciplinary multidisciplinary group for a maximum of three iterative *** degree of agreement was scored on a numeric 0–10 *** consensus was defined as a score≥8 for≥80%of the *** Eleven scientific societies(3 radiological and 8 surgical)endorsed the *** three rounds of voting,the experts(69 colorectal surgeons,23 radiologists,2 anatomists,and 1 gastroenterologist)achieved consensus for 12 of 14 statements(85.7%).Based on the results of the Delphi process,the six following features of anal fistulas were included in the SMART:Primary tract,secondary extension,internal opening,presence of collection,coexisting le-sions,and sphincters *** A structured template,SMART,was developed to standardize imaging reporting of fistula-in-ano in a simple,systematic,time-efficient way,providing the minimum dataset of information and visual diagram useful to refer-ring physicians.

关键词： Anal fistulas Fistula-in-ano Template Reporting Magnetic resonance imaging Endoanal ultrasound

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Clinical pharmacology relevant to older adults with cardiovascular disease

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Journal of Geriatric Cardiology 2015年第3期12卷 192-195页

作者： Jorge A Brenes-Salazar Laith Alshawabkeh Kenneth E Schmader Joseph T Hanlon Daniel E Forman department of medicine Division of Cardiovascular Diseases Mayo Clinic Rochester MN USA department of medicine Division of Cardiovascular Medicine University of lowa Iowa City IA USA department of medicine Division of Geriatrics Duke University School of Medicine Durham NC USA departments of medicine (division of Geriatric medicine) Pharmacy and Epidemiology University of Pittsburgh Geriatric Research Education and Clini- cal Center and Center for Health Equity Research and Promotion VA Pittsburgh Health System Pittsburgh PA USA department of medicine (divisions of Geriatric medicine and Cardiology) University of Pittsburgh Medical Center Geriatric Research Education and Clinical Center VA Pittsburgh Health System Pittsburgh PA USA

1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.

关键词： Metabolism Pharmacokinetics Pharmacodynamics Polypharmacy

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What Should We Focus on in Sepsis Fluid Resuscitation?--A Research Based on Scientometrics and Visual Analysis

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Biomedical and Environmental Sciences 2022年第2期35卷 155-160页

作者： HE Xiao Jun ZHU Xiang MA Yue Feng LIANG Jun department of Emergency medicine Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009Zhejiang China department of geriatrics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001AnhuiChina IT Center Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009ZhejiangChina

Sepsis is a life-threatening condition and a global disease *** syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection,with renewed emphasis on the immune *** worldwide constantly update the diagnostic criteria of sepsis and have introduced concepts such as“sepsis-3”“Surviving Sepsis Campaign(SSC)”“Early Goal-Directed Therapy(EGDT)”,the 3-h and 6-h bundles to an hour-1 bundle[1],“limited ventilation”“the best PEEP[2]”,and“Lung Protective-Ventilation”.Despite all efforts of experimental and clinical research during the last three decades,the ability to positively influence the course and outcome of the syndrome remains limited.

关键词： Sepsis PEEP Focus

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Life Space Assessment in Older Women Undergoing Non-Surgical Treatment for Urinary Incontinence

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Open Journal of Obstetrics and Gynecology 2014年第14期4卷 809-816页

作者： Thomas L. Wheeler II Jana D. Illston Alayne D. Markland Patricia S. Goode Holly E. Richter department of Obstetrics and Gynecology University of South Carolina School of Medicine-Greenville Greenville USA division of Gerontology Geriatrics and Palliative Care University of Alabama at Birmingham Birmingham USA department of Obstetrics and Gynecology University of Alabama at Birmingham Birmingham USA

Objective: Urinary incontinence (UI) impacts all aspects of life activities. This study aims to characterize change in mobility within the community utilizing the Life Space Assessment (LSA) questionnaire in women undergoing non-surgical UI treatment. Methods: This prospective cohort study, performed from July 2007 to March 2009, followed women seeking non-surgical UI treatment from an outpatient tertiary-care clinic and assessed their mobility and symptoms using LSA, Urogenital Distress Inventory (UDI-6), and Incontinence Impact Questionnaire (IIQ-7) at baseline and 2, 6, and 12 months post-treatment. Estimated Percent Improvement (EPI) and Patient Satisfaction Question (PSQ) were obtained post-treatment. The women were treated with multi-component behavioral and/or pharmacologic therapies, and we hypothesized that LSA would improve with treatment. Repeated measures analysis with Tukey’s HSD and backwards selection linear regression model were performed. Results: 70 ambulatory, community-dwelling women, aged 65 years or older, seeking non-surgical care for UI were recruited. LSA score decreased from baseline to 2 months (mean ± SD;63 ± 29 to 56 ± 28, p < 0.001) and was sustained at 6 and 12 months (54 ± 28, 54 ± 28). UDI scores improved from 36 ± 23 to 25 ± 24, p < 0.001, at 2 months, and improvement persisted at 6 and 12 months (22 ± 22, 21 ± 24). Improvements in UDI and patient perceived improvement in UI were not associated with LSA change. Age, race, and depression impacted LSA, which decreased 1-point for each additional year of age (p = 0.004), 6-points for each point higher on the Geriatric Depression Scale (GDS) (p = 0.002), and 6-point for African American race (p = 0.048). Conclusion: Decreased mobility represented by LSA was related to age, depression, and race, but not UI symptom improvement.

关键词： Urinary Incontinence Life-Space Depression Mobility Community-Dwelling Women

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