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Higher Groundwater Selenium exposure Is Associated with Better Memory: A Project FRONTIeR Study

Neuroscience & Medicine 2012年第1期3卷 18-25页

作者： James Hall Melissa edwards Robert Barber leigh Johnson Gordon Gong Sid e. O’Bryant Department of Neurology Texas Tech University Health Sciences Center Lubbock TX USA Department of Psychology Texas Tech University Lubbock TX USA F. Marie Hall Institute for Rural and Community Health Texas Tech Health Sciences Center Lubbock TX USA Texas Tech University Health Sciences Center Laura W Bush Institute for Women’s Health & Department of Family and Community Medicine Lubbock TX USA University of North Texas Health Science Center Department of Pharmacology and Neuroscience Ft Worth TX USA University of North Texas Health Science Center Department of Psychiatry Ft. Worth TX USA

Background: exposure to elements in groundwater (toxic or beneficial) is commonplace yet, outside of lead and mercury, little research has examined the impact of many commonly occurring exposures on mental abilities during the aging process. Selenium has antioxidant properties as part of the glutathione peroxidase system and may have protective effects on memory abilities. Objectives: To investigate the relationship of groundwater selenium exposure to neuropsychological status. Method: Analysis of data from 484 participants (148 men and 336 women) of Project FRONTIeR, a community-based participatory research study of the epidemiology of health issues of rural-dwelling adults and elders. Results: estimated selenium exposure (current and long-term) was specifically related to memory functioning without relation to other neurocognitive domains. The significant, positive link between selenium and memory (Immediate and Delayed) scores held regardless of APOe4 status as well as when the sample was restricted to only those without cognitive dysfunction. Current selenium was also associated with significantly reduced risk of cognitive decline prospectively. Conclusions: Higher selenium levels were associated with better memory functioning as well as reduced risk of cognitive decline among this community-based sample. Given the antioxidant properties of selenium, and the well-documented link between oxidative stress and the development of cognitive dysfunction and Alzheimer’s disease, additional research is necessary to determine the utility of groundwater selenium monitoring as a potential population-wide prevention effort against Alzheimer’s disease.

关键词： environmental exposure Cognition APOe4 Selenium Groundwater

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Medication beliefs predict medication adherence in ambulatory patients with decompensated cirrhosis

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World Journal of Gastroenterology 2017年第40期23卷 7321-7331页

作者： Kelly L Hayward Patricia C Valery Jennifer H Martin Antara Karmakar Preya J Patel leigh U Horsfall Caroline J Tallis Katherine A Stuart Penny L Wright David D Smith Katharine M Irvine elizabeth e Powell W Neil Cottrell Pharmacy Department Princess Al-exandra Hospital The Centre for Liver Disease Research Translational Research Institute The University of Queensland Cancer and Chronic Disease Research Group QIMR Berghofer Medical Research Institute School of Medicine and Public Health The University of Newcastle The Centre for Liver Disease Research Translational Research Institute The University of Queensland Department of Gastroenterology and Hepatology Princess Alexandra Hospital The Centre for Liver Disease Research Translational Research Institute The University of Queensland Department of Gastroenterology and Hepatology Princess Alexandra Hospital Statistics Unit QIMR Berghofer Medical Research Institute School of Pharmacy The University of Queensland

AIM To investigate the impact of medication beliefs, illness perceptions and quality of life on medication adherence in people with decompensated *** One hundred adults with decompensated cirrhosis completed a structured questionnaire when they attended for routine outpatient hepatology review. Measures of self-reported medication adherence(Morisky Medication Adherence Scale), beliefs surrounding medications(Beliefs about Medicines Questionnaire), perceptions of illness and medicines(Brief Illness Perception Questionnaire), and quality of life(Chronic Liver Disease Questionnaire) were examined. Clinical data were obtained via patient history and review of medical records. Least absolute shrinkage and selection operator and stepwise backwards regression techniques were used to construct the multivariable logistic regression model. Statistical significance was set at alpha = *** Medication adherence was " High " in 42 % o f participants, "Medium" in 37%, and "Low" in 21%. Compared to patients with "High" adherence, those with "Medium" or "Low" adherence were more likely to report difficulty affording their medications(P er perception of treatment helpfulness(P = 0.003) and stronger medication concerns relative to medication necessity beliefs(P = 0.003). People with "Low" adherence also experienced greater symptom burden and poorer quality of life, including more frequent abdominal pain(P = 0.023), shortness of breath(P = 0.030), and emotional disturbances(P = 0.050). Multivariable analysis identified having stronger medication concerns relative to necessity beliefs(Necessity-Concerns Differential ≤ 5, OR = 3.66, 95%CI: 1.18-11.40) and more frequent shortness of breath(shortness of breath score ≤ 3, OR = 3.87,95%CI: 1.22-12.25) as independent predictors of "Low"*** The association between "Low" adherence and patients having strong concerns or doubting the necessity or helpfulness of their medications should be explor

关键词： Medication adherence Medication beliefs Illness perceptions Quality of life Liver cirrhosis

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Depression and Brain-derived Neurotrophic Factor Levels in Alzheimer's Disease

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Neuroscience & Medicine 2011年第1期2卷 43-47页

作者： James R. Hall Sid e. O'Bryant leigh Johnson Robert C. Barber 不详

Background: Depression is often viewed as a risk factor for the development of Alzheimer's disease (AD), however little is known regarding the underlying biological mechanisms linking these two diseases. Brain-derived neurotrophic factor (BDNF) has been linked to both cognitive impairment and depression in past research;however few studies have ex-amined this relation in a sample of Alzheimer's patients. The present study sought to address this gap in the literature by examining the relation between serum BDNF levels and depression assessed by the Geriatric Depression Scale (GDS) in a group of patients diagnosed with probable Alzheimer's disease. Methods: Participants included 169 individuals diagnosed with Probable AD enrolled in the TARC Longitudinal Research Cohort with available BDNF levels and GDS scores. The participants were divided into Depressed (N = 20) and Not Depressed (N = 149) based on GDS scores. Re-sults: BDNF levels significantly predicted level (High vs. Low) of depression (β = 0.066, Se = 0.031, p = 0.034). BDNF levels for the Depressed group were significantly higher than those observed in the Not Depressed group (p. > 0.036). Conclusions: These findings suggest that an upregulation of BDNF possibly exists among depressed AD patients as a response to the chronic inflammatory processes that occur in depression. This upregulation of BDNF appears to persist at least into early stages of Alzheimer's.

关键词： Alzheimer's Disease Depression BDNF Depression Severity

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Clinical Observations on the effects of a Dietary Supplement (GI Regenerate<sup>TM</sup>) on Patients’ Gastrointestinal Symptoms and Quality of Life Assessments

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International Journal of Clinical Medicine 2020年第5期11卷 303-315页

作者： leigh e. Connealy Robert Settineri Ariel Causey Ashley Athanas Kathleen McCall-Smith Jason Clark Christine e. McLaren Garth L. Nicolson Center for New Medicine Irvine USA Sierra Productions Research Irvine USA Statistical Unit Department of Medicine University of California Irvine School of Medicine Irvine USA Department of Molecular Pathology The Institute for Molecular Medicine Huntington Beach USA

Background: Different treatments have been developed and used to control symptoms and improve quality of life in patients with digestive diseases and disorders. Although the use of drugs or alternative approaches has improved symptom severity in some but not all patients, often these improvements were not sustainable. Objectives: An open label clinical study was initiated to determine if oral capsules containing a dietary supplement of herbs and oils (GI RegenerateTM) could reduce self-reported gastrointestinal symptoms and improve quality of life (QOL) indicators in patients with gastrointestinal conditions. Methods: Participants included 50 patients (40 females and 10 males) of mean age of 51.1 ± 12.7 years (range, 24 - 77 years) with a diagnosis of a gastrointestinal disorder or gastrointestinal symptoms. These patients consumed five soft-gels containing the test supplement 30 minutes before each meal for 90 days. Symptoms were evaluated by medical staff, and patient health status was self-reported using a validated quality of life questionnaire (Quality of Life Digestive Survey) designed for functional digestive disorders. exit interviews (Patient Global Impression of Change, PGIC) were conducted by the medical staff. Results: Participants in the study responded with improved symptom severities and QOL scores to the test dietary supplement within the 90 day period;most improvements occurred within 20 days on the test dietary supplement. By the end of the study there were significant overall global improvements in the symptoms and QOL health surveys (p = 0.0183), with significant improvements in symptom discomfort (p = 0.0004), daily activities (p = 0.029) and anxiety (p = 0.018). In contrast, there were insignificant improvements in diet (p = 0.398), sleep (p = 0.136), health perception (p = 0.686), coping with the disease (p = 0.309) and impact of stress (p = 0.785). Using the PGIC exit interview that measured each patient’s impression of overall global change

关键词： Gastrointestinal Symptoms Quality of Life Dietary Supplement Digestive Disorders Herbal Remedies Dietary Oils

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High-throughput calculations of charged point defect properties with semi-local density functional theory— performance benchmarks for materials screening applications

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npj Computational Materials 2023年第1期9卷 1628-1639页

作者： Danny Broberg Kyle Bystrom Shivani Srivastava Diana Dahliah Benjamin A.D.Williamson leigh Weston David O.Scanlon Gian-Marco Rignanese Shyam Dwaraknath Joel Varley Kristin A.Persson Mark Asta Geoffroy Hautier Materials Sciences Division Lawrence Berkeley National Laboratory1 Cyclotron RoadBerkeleyCA 94720USA Department of Materials Science and engineering University of CaliforniaBerkeleyCA 94720USA John A.Paulson School of engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA Department of Physics An-Najah National UniversityNablusPalestine Institute of Condensed Matter and Nanosciences UniversitéCatholique de LouvainChemin desÉtoiles 8B-1348 Louvain-la-NeuveBelgium Department of Materials Science and engineering NTNU Norwegian University of Science and TechnologyTrondheimNorway energy Technologies Area Lawrence Berkeley National Laboratory1 Cyclotron RoadBerkeleyCA 94720USA Department of Chemistry University College London20 Gordon StreetLondon WC1H 0AJUK Thomas Young Centre University College LondonGower StreetLondon WC1E 6BTUK Diamond Light Source Ltd. Diamond HouseHarwell Science and Innovation CampusDidcotOxfordshire OX110DEUK Lawrence Livermore National Laboratory LivermoreCA 94550USA Molecular Foundry Lawrence Berkeley National Laboratory1 Cyclotron RoadBerkeleyCA 94720USA Thayer School of engineering Dartmouth CollegeHanoverNH 03755USA

Calculations of point defect energetics with Density Functional Theory(DFT)can provide valuable insight into several optoelectronic,thermodynamic,and kinetic *** calculations commonly use methods ranging from semi-local functionals with a-posteriori corrections to more computationally intensive hybrid functional *** applications of DFT-based high-throughput computation for data-driven materials discovery,point defect properties are of interest,yet are currently excluded from available materials *** work presents a benchmark analysis of automated,semi-local point defect calculations with a-posteriori corrections,compared to 245“gold standard”hybrid calculations previously *** consider three different a-posteriori correction sets implemented in an automated workflow,and evaluate the qualitative and quantitative differences among four different categories of defect information:thermodynamic transition levels,formation energies,Fermi levels,and dopability *** highlight qualitative information that can be extracted from high-throughput calculations based on semi-local DFT methods,while also demonstrating the limits of quantitative accuracy.

关键词： properties defect correction

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Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop via NRF2 in cancer therapeutic resistance

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1871-1884页

作者： Hong Wang Qianqian Wang Guodi Cai Zhijian Duan Zoann Nugent Jie Huang Jianwei Zheng Alexander D.Borowsky Jian Jian Li Peiqing Liu Hsing-Jien Kung leigh Murphy Hong-Wu Chen Junjian Wang School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Department of Biochemistry and Molecular Medicine University of CaliforniaDavisSacramentoCA 95817USA Research Institute in Oncology and Hematology University of Manitoba and CancerCare ManitobaWinnipeg R3E 0V9Canada Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital and Guangdong Academy of Medical SciencesGuangzhou 510080China Department of Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCA 95817USA Department of Radiation Oncology University of CaliforniaDavisSacramentoCA 95817USA National-Local Joint engineering Laboratory of Druggability and New Drugs evaluation Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510006China UC Davis Comprehensive Cancer Center School of MedicineUniversity of CaliforniaDavisSacramentoCA 95817USA

Metabolic and epigenetic reprogramming play important roles in cancer therapeutic ***,their interplays are poorly *** report here that elevated TIGAR(TP53-induced glycolysis and apoptosis regulator),an antioxidant and glucose metabolic regulator and a target of oncogenic histone methyltransferase NSD2(nuclear receptor binding SeT domain protein 2),is mainly localized in the nucleus of therapeutic resistant tumor cells where it stimulates NSD2 expression and elevates global H3K36me2 ***,TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2,H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new(NSD2)and established(NQO1/2,PRDX1 and GSTM4)targets of NRF2,independent of its enzymatic *** TIGAR confers cancer cell resistance to chemotherapy and hormonal therapy in vitro and in tumors through effective maintenance of redox *** addition,nuclear accumulation of TIGAR is positively associated with NSD2 expression in clinical tumors and strongly correlated with poor *** findings define a nuclear TIGAR-mediated epigenetic autoregulatory loop in redox rebalance for tumor therapeutic resistance.

关键词： TIGAR NSD2 NRF2 Metabolism Oxidative stress epigenetic reprogramming Therapeutic resistance Redox homeostasis

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Biomarkers and Depressive Symptoms in a Sample of Cognitively Intact and Alzheimer’s Disease elderly Males

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Neuroscience & Medicine 2011年第4期2卷 306-312页

作者： James R. Hall Hoa T. Vo leigh A. Johnson Scott Winter Robert C. Barber Sid e. O’Bryant 不详

Serum-based biomarkers and GDS-30 score and subscales of depressive symptoms were examined in a cross-sectional sample of 81 elderly men drawn from the TARCC cohort. Measurements included neuropsychological assessment and serum. Thirty three patients met consensus diagnosis for probable AD and forty eight were cognitively intact. Although initial regression analysis of all subjects showed significant relationships between depression and specific biomarkers, analyses based on diagnosis indicated that none of the biomarkers were significantly associated with depression among the controls. Among AD males MIF was significantly associated with total GDS scores and subscales of dysphoria, meaninglessness, and cognitive impairment. TNF-α was significantly associated with the apathy in AD males. Higher levels of MIF were associated with less depression in AD men. TNF-α was positively associated with degree of apathy. This study suggests the importance of cognitive status, gender and subtypes of depression when investigating biomarkers and depression in the elderly.

关键词： Depression Biomarkers Alzheimer’s

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Biomarkers and Depressive Symptoms in Older Women with and without Cognitive Impairment

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Journal of Behavioral and Brain Science 2012年第2期2卷 276-281页

作者： James R. Hall leigh A. Johnson Hoa T. Vo Robert C. Barber A. Scott Winter Sid e. O’Bryant Department of Internal Medicine University of North Texas Health Sciences Center Fort Worth USA Department of Pharmacology and Neuroscience University of North Texas Health Sciences Center Fort Worth USA Department of Psychiatry Behavioral Health and Neuroscience University of North Texas Health Sciences Center Fort Worth USA Institute of Aging and Alzheimer’s Disease Research University of North Texas Health Sciences Center Fort Worth USA

A number of biological markers have been implicated in late life depression with inconsistent results. The present study examined the relationship between several serum based biomarkers and symptoms of depression in a sample of elderly women with AD or cognitively intact. Methods 171 females (58 with AD and 113 cognitively intact) were recruited from the Longitudinal Research Cohort of the Texas Alzheimer’s Research and Consortium (TARC). Stepwise regressions were conducted with GDS total and subscales and a panel of biomarkers (CRP, IL-10, IL-1α, TNF-α, ICAM-1, BDNF, and MIF). Apoe4 status was coded (carrier or non-carrier), and the results were analyzed by cognitive status (AD or controls). Results: None of the biomarkers significantly predicted total GDS score for AD cases, controls or sample as a whole. For the Controls, ICAM significantly predicted Dysphoria and level of Apathy. Among AD patients, MIF, ICAM, and CRP, were significantly associated with Apathy. MIF and ICAM were inversely associated with reported Apathy. CRP was positively associated with Apathy. CRP was also positively related to level of perceived Cognitive Impairment. Conclusions: The present study was one of the first to examine biomarkers related to depression symptoms in elderly women with AD and normal controls. For Controls ICAM alone predicted level of apathy. In the AD group, MIF, CRP, and ICAM were significantly associated with apathy. More research examining the relationship between biomarkers and depression is needed in older patients with and without cognitive impairment across genders.

关键词： Biomarkers Depression Alzheimer’s Disease Gender

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Complex Molecular Knots and Links

Complex Molecular Knots and Links

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全国第十六届大环化学暨第八届超分子化学学术讨论会

作者： Jean-Francois Ayme Jonathon e.Beves David A.leigh Kari Rissanen Roy M.McBumey David Schultz Key State Laboratory for Coordination Chemistry School of Chemistry and Chemical EngineeringNanjing University Department of Chemistry Nanoscience CenterUniversity of Jyvskyl

＜正＞The presence of knots and links in biological systems（proteins and other biopolymers） has been shown to be crucial to their stability and ***,in synthetic systems the entanglements of polymers significantly alters their properties both through mechanical cross linking,and also though strand weakening by the presence of knotted ***,the molecular level challenge to form precise topologies remains unconquered by chemists! Supramolecular strategies lie at the forefront of methods towards this goal,by allowing the templating of crossing points and the means to control the formation of

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源于香港的H_5N_1型禽流感病毒对鸸鹋、鹅、鸭和鸽子的致病性

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山东家禽 2002年第12期15卷 45-46页

作者：王友信 Laura e.leigh Perkins David e.suayne 山东农业大学动科院泰安271018

A型禽流感病毒(AIV)天然存在于各种水鸟,并可通过各种水鸟周期性地传播到其它鸟类和哺乳动物,包括人类中.

关键词：症状病理变化抗原分布人工接种鸡 H5N1型禽流感病毒鸸鹋鹅鸭鸽子致病性

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