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Association of cardiovascular system medications with cognitive function and dementia in older adults living in nursing homes in Australia

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Journal of Geriatric Cardiology 2017年第6期14卷 407-415页

作者： Enwu liu Suzanne M Dyer lisa Kouladjian O'Donnell Rachel Milte Clare Bradley stephanie l Harrison Emmanuel Gnanamanickam Craig Whitehead Maria Crotty Department of Rehabilitation Aged and Extended Care Faculty of Medicine Nursing and Health Sciences School of Health Sciences Flinders University Daw Park Australia NHMRC Cognitive Partnership Centre The University of Sydney Sydney NSW Australia Kolling Institute of Medical Research St Leonards NSW Australia and Sydney Medical School University of Sydney Sydney NSW Australia Institute for Choice University of South Australia GPO Box 2471 Adelaide SA Australia Infection & Immunity - Aboriginal Health SAHMRI PO Box 11060 Adelaide SA Australia

Objective To examine associations between cardiovascular system medication use with cognition function and diagnosis of dementia in older adults living in nursing homes in Australia. Methods As part of a cross-sectional study of 17 Australian nursing homes examining quality of life and resource use, we examined the association between cognitive impairment and cardiovascular medication use （identified using the Anatomical Therapeutic Classification System） using general linear regression and logistic regression models. People who were receiving end of life care were excluded. Results Participants included 541 residents with a mean age of 85.5 years （± 8.5）, a mean Psychogeriatric Assessment Scale–Cognitive Impairment （PAS-Cog） score of 13.3 （± 7.7）, a prevalence of cardiovascular diseases of 44% and of hypertension of 47%. Sixty-four percent of participants had been diagnosed with dementia and 72% had received cardiovascular system medications within the previous 12 months. Regression models demonstrated the use of cardiovascular medications was associated with lower （better） PAS-Cog scores [Coefficient （β） = -3.7; 95% CI： -5.2 to -2.2; P 〈 0.0001] and a lower probability of a dementia diagnosis （OR = 0.44; 95% CI： 0.26 to 0.75, P = 0.0022）. Analysis by subgroups of medications showed cardiac therapy medications （C01）, beta blocking agents （C07）, and renin-angiotensin system agents （C09） were associated with lower PAS-Cog scores （better cognition） and lower dementia diagnosis probability. Conclusions This analysis has demonstrated an association between greater cardiovascular system medication use and better cognitive status among older adults living in nursing homes. In this population, there may be differential access to health care and treatment of cardiovascular risk factors. This association warrants further investigation in large cohort studies.

关键词： Cardiovascular agents Cognitive dysfunction Dementia Residential facilities

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Tameness does not correlate with the learning of an appetitive association in a wild canid

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Current Zoology 2019年第1期65卷 61-65页

作者： Matthew B. Petelle stephanie Periquet Aliza le Roux Department of Zoology and Entomology University of Free State Qwaqwa Campus Private Bag X13 Phuthaditjhaba Free State 9866 South Africa

Individual differe nces in cog nition have been shown to be common in some animal taxa, and recent evidenee suggests that an individual's personality can be associated with an individuads cognitive strategy. We tested whether wild bat-eared foxes Otocyon megalotis differ in a risktaking behavior (tameness) and whether this trait correlated with appetitive association learning performanee. While our result shows that individuals differed in their tameness, we found no associati on between this personality trait and learning the appetitive association. This result does not support the framework that differe nces in cog nition are associated with differe nces in personality;however, our small sample size does not allow us to assert that pers on ality can not be associated with cog nition in this system. This study highlights that measuri ng cog nition and pers on ality in wild systems presents added difficulty and that correlations found in captive animals may not be evident in their wild counterparts.

关键词： carnivore cognition bat-eared fox personality Individuals

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A CK2-RNF4 interplay coordinates non-canonical SUMOylation and degradation of nuclear receptor FXR

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Journal of Molecular Cell Biology 2017年第3期9卷 195-208页

作者： stephanie Bilodeau Veronique Caron Jonathan Gagnon Alexandre Kuftedjian Andre Tremblay Research Center CHU Sainte-Justine Montreal Quebec H3T 1C5 Canada Department of Biochemistry and Molecular Medicine Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada Department of Obstetrics & Gynecology Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada

Farnesoid X receptor （FXR） is a ligand-activated nuclear receptor that plays a central role in regulating genes involved in bile acid homeostasis, and fat and glucose metabolism. Here, we demonstrate a post-translational interplay between FXR phosphoryl- ation, SUMOylation, and ubiquitination that directs the receptor into an activation-degradation pathway in hepatocytes. We iden- tify a non-canonical SUMOylation motif termed pSuM that conjugates SUM02 at lys-325 of FXR under the direct control of casein kinase 2 （CK2）, which provides the required negative charge for Ubc9 and PIAS1 to perform SUMOylation, by phosphorylating Ser-327. lys-325 SUMOylation is indispensable to the promotion of efficient ligand activation and transcriptional coactivation of FXR. Constitutive pSuM activation using a phospho-mimic Ser-327 mutant or catalytic CK2 expression strongly induces SUM02 conjugation, which directs FXR ubiquitination and proteasome-dependent degradation. We also determine that such SUMOylation-dependent ubiquitination of FXR is mediated by the E3 ubiquitin ligase RNF4, which is required to achieve maximal induction of FXR and optimal up- or downregulation of responsive genes involved in bile acid homeostasis and liver regeneration. Our findings identify a highly regulated atypical SUMO conjugation motif that serves to coordinate FXR transcriptional compe- tence, thereby expanding the intricate dynamics of the SUMOylation process used by incoming signals to govern metabolic gene regulation.

关键词： farnesoid receptor SUMOylation ubiquitination 26S proteasome bile acid

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Caring for the breast cancer survivor's health and wellbeing

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World Journal of Clinical Oncology 2014年第4期5卷 693-704页

作者： Petra M Casey stephanie S Faubion Kathy l Mac laughlin Margaret E long Sandhya Pruthi Department of Obstetrics and Gynecology Mayo Clinic Rochester MN 55905 United States Women’s Health Clinic Department of Internal Medicine Mayo Clinic Rochester MN 55905 United States Department of Family Medicine Mayo Clinic Rochester MN 55905 United States Department of Internal Medicine and Breast Clinic Mayo Clinic Rochester MN 55905 United States

The breast cancer care continuum entails detection, diagnosis, treatment, and survivorship. During this time, focus on the whole woman and medical concerns beyond the breast cancer diagnosis itself is essential. In this comprehensive review, we critically review and evaluate recent evidence regarding several topics pertinent to and specific for the woman living with a prior history of breast cancer. More specifically, we discuss the most recent recommendations for contraceptive options including long-acting reversible contraception and emergency contraception, fertility and pregnancy considerations during and after breast cancer treatment, management of menopausal vasomotors symptomsand vulvovaginal atrophy which often occurs even in young women during treatment for breast cancer. The need to directly query the patient about these concerns is emphasized. Our focus is on non-systemic hormones and non-hormonal options. Our holistic approach to the care of the breast cancer survivor includes such preventive health issues as sexual and bone health,which are important in optimizing quality of life. We also discuss strategies for breast cancer recurrence surveillance in the setting of a prior breast cancer diagnosis. This review is intended for primary care practitioners as well as specialists caring for female breast cancer survivors and includes key points for evidence-based best practice recommendations.

关键词： Breast cancer Contraception Vasomotor symptoms Vulvovaginal atrophy Sexual health Osteopenia Osteoporosis Breast cancer recurrence Breast cancer surveillance

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Fused-core particle technology in high-performance liquid chromatography: An overview

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Journal of Pharmaceutical Analysis 2013年第5期3卷 303-312页

作者： Joseph J.Kirkland stephanie A.Schuster William l.Johnson Barry E.Boyes Advanced Materials Technology Inc. Complex Carbohydrate Research Center

The advent of superficially porous particles （SPPs） for packed HPlC columns has changed the way that many practitioners have approached the problem of developing needed separations. The very high efficiency of such columns, combined with convenient operating conditions, modest back pressures and the ability to use conventional HPlC instruments has resulted in intense basic studies of SPP technology, and widespread applications in many sciences. This report contains an overview of the SPP technology first developed in 2006 by Advanced Materials Technology, Inc., for sub-3-11m particles, then expanded into a family of SPP products with different particle sizes, pore sizes and other physical parameters. This approach was designed so that each particle of the family could be optimized for separating a particular group of compounds, usually based on solute size.

关键词： Superfcially porous particles Fused-core particles Core–shell particles Peptides Proteins Drug separations

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The effect of self-employment on health, access to care, and health behavior

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Health 2013年第12期5卷 2116-2127页

作者： Jangho Yoon stephanie l. Bernell Health Management and Policy Program College of Public Health and Human Sciences Oregon State University Corvallis USA

The focus of this paper is to investigate the role self-employment conceptualized as a lifestyle factor on health, access to health care, and health behaviors. We analyze rich data on 13,435 working adults in the US, who are either selfemployed or salaried workers. Outcomes include physical and mental health perception, validated indexes of physical and mental health, and medical conditions;access-to-care measures such as a barrier to obtaining necessary health care;and health behaviors such as smoking, physical activity and body mass index. Instrumental variables methods are used to correct for selection into self-employment. We find that self-employment is positively associated with perceived physical health, and is negatively associated with having diabetes, high blood pressure, high cholesterol and arthritis. No mental health outcome is significantly associated with self-employment. There is no significant difference between self-employed and wage-earning individuals with regard to access to care. Self-employed individuals are less likely to smoke, and are more likely to participate in physical activity and have normal-weight. We conclude that despite lack of health insurance, self-employed persons in the US are as healthy as wage-earners, do not experience a greater barrier to access to care, and are more likely to engage in healthy behavior.

关键词： Self-Employment Health Health Behavior Access to Care Health Determinant

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Evaluation of Sensory Properties of Probiotic Yogurt Containing Food Products with Prebiotic Fibresin Mwanza, Tanzania

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Food and Nutrition Sciences 2011年第5期2卷 434-439页

作者： stephanie l. Irvine Sharareh Hekmat 不详

Yogurt becomes a functional food upon incorporating probiotics-live microorganisms which when adequately administered confer health benefits. Prebiotics are fermentable fibres that nourish beneficial gastrointestinal microflora enhance the functionality of probiotics. This research aimed to improve the acceptability and functionality of probiotic yogurt produced in Mwanza, Tanzania by incorporating probiotic food ingredients. The probiotic culture lactobacillus rhamnosus GR-1 and standard yogurt cultures lactobacillus delbrueckii bulgaricus and Steptococcus thermophilus were used to manufacture yogurt, then locally available prebiotic food ingredients containing fructooligosaccha- ride/inulin were incorporated. A nine-point facial hedonic scale was used to evaluate five yogurt samples. A mean score between one and three indicated that the sample product was well accepted. Probiotic yogurt containing onions, garlic and sweet potato received a score of 1.6 ± 0.84 (p 0.90), and plantains, 5.3 ± 2.56 (p > 0.90) were not well accepted. Sweet, mildly flavored prebiotic ingredients were most successfully incorpo- rated into probiotic yogurt in Mwanza.

关键词： Probiotics Prebiotics Yogurt Functional Food

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Inflammation-associated microsatellite alterations:Mechanisms and significance in the prognosis of patients with colorectal cancer

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World Journal of Gastrointestinal Oncology 2018年第1期10卷 1-14页

作者： Minoru Koi stephanie S Tseng-Rogenski John M Carethers Department of Internal Medicine and Comprehensive Cancer Center University of MichiganAnn ArborMI 48109-5368United States

Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MlH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic nonMSI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as MSIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-l/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.

关键词： Microsatellite instability Microsatellite stable Elevated microsatellite alterations at selected tetranucleotide repeats Colorectal cancer Mismatch repair Inflammation MSH3

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Expression of the human TSPY gene in the brains of transgenic mice suggests a potential role of this Y chromosome gene in neural functions

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Journal of Genetics and Genomics 2011年第5期38卷 181-191页

作者： Tatsuo Kido stephanie Schubert Jrg Schmidtke Yun-Fai Chris lau Division of Cell and Developmental Genetics Department of MedicineVA Medical Centerand Institute for Human GeneticsUniversity of California Institute of Human Genetics Hannover Medical School

The testis specific protein Y-encoded （TSPY） is a member of TSPY/SET/NAP1 superfamily, encoded within the gonadoblastoma locus on the Y chromosome. TSPY shares a highly conserved SET/NAP-domain responsible for protein--protein interaction among TSPY/SET/NAP 1 proteins. Accumulating data, so far, support the role of TSPYas the gonadoblastoma gene, involved in germ cell tumorigenesis. The X-chromosome homolog of TSPY, TSPX is expressed in various tissues at both fetal and adult stages, including the brain, and is capable of interacting with the multi-domain adapter protein CASK, thereby influencing the synaptic and transcriptional functions and developmental regulation of CASK in the brain and other neural tissues. Similar to TSPX, we demonstrated that TSPY could interact with CASK at its SET/NAP-domain in cultured cells. Transgenic mice harboring a human TSPYgene and flanking sequences showed specific expression of the human TSPYtransgene in both testis and brain. The neural expression pattern of the human TSPYgene overlapped with those of the endogenous mouse Cask and Tspx gene. Similarly with TSPX, TSPY was co-localized with CASK in neuronal axon fibers in the brain, suggesting a potential role（s） of TSPY in development and/or physiology of the nervous system.

关键词： TSPY TSPX CASK Y chromosome Neuron Testis

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FC-DIRECTED ANTIBODY CONJUGATION OF MAGNETIC NANOPARTIClES FOR ENHANCED MOlECUlAR TARGETING

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 387-396页

作者： ROBABEH REZAEIPOOR RENU JOHN STEVEN G.ADIE ERIC J.CHANEY MARINA MARJANOVIC AMY l.OlDENBURG stephanie A.RINNE STEPHEN A.BOPPART Biophotonics Imaging laboratory Beckman Institute for Advanced Science and Technology University of Illinois at Urbana-Champaign UrbanaILUSA Departments of Electrical and Computer Engineering Bioengineeringand Internal Medicine University of Illinois at Urbana-Champaign UrbanaILUSA

In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs)functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody totarget the tumor antigen HER2. The Fc-directed conjugation of antibodies to the MNPs aidstheir efficient immunospecific targeting through free Fab portions. The directional specificity ofconjugation was verified on a macrophage cell line. Immunofluorescence studies on macrophagestreated with functionalized MNPs and free anti-HER2 antibody revealed that the antibodymolecules bind to the MNPs predominantly through their Fc portion. Different cell lines with different HER2 expression levels were used to test the specificity of our functionalized nanoprobe formolecular targeting applications. The results of cell line targeting demonstrate that these engineered MNPs are able to differentiate between cell lines with different levels of HER2 expression.

关键词： Nanoprobe molecular imaging cancer

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