Showing papers by "University of Kentucky published in 2007"

Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria

Abstract: The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid beta as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.

Does tailoring matter? Meta-analytic review of tailored print health behavior change interventions.

Abstract: Although there is a large and growing literature on tailored print health behavior change interventions, it is currently not known if or to what extent tailoring works. The current study provides a meta-analytic review of this literature, with a primary focus on the effects of tailoring. A comprehensive search strategy yielded 57 studies that met inclusion criteria. Those studies-which contained a cumulative N = 58,454-were subsequently meta-analyzed. The sample size-weighted mean effect size of the effects of tailoring on health behavior change was found to be r = .074. Variables that were found to significantly moderate the effect included (a) type of comparison condition, (b) health behavior, (c) type of participant population (both type of recruitment and country of sample), (d) type of print material, (e) number of intervention contacts, (f) length of follow-up, (g) number and type of theoretical concepts tailored on, and (h) whether demographics and/or behavior were tailored on. Implications of these results are discussed and future directions for research on tailored health messages and interventions are offered.

Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity

Abstract: At the end of the 1980s, it was clearly demonstrated that cells produce nitric oxide and that this gaseous molecule is involved in the regulation of the cardiovascular, immune and nervous systems, rather than simply being a toxic pollutant. In the CNS, nitric oxide has an array of functions, such as the regulation of synaptic plasticity, the sleep-wake cycle and hormone secretion. Particularly interesting is the role of nitric oxide as a Janus molecule in the cell death or survival mechanisms in brain cells. In fact, physiological amounts of this gas are neuroprotective, whereas higher concentrations are clearly neurotoxic.

Integration of impulsivity and positive mood to predict risky behavior: Development and validation of a measure of positive urgency.

Abstract: In 3 studies, the authors developed and began to validate a measure of the propensity to act rashly in response to positive affective states (positive urgency). In Study 1, they developed a content-valid 14-item scale, showed that the measure was unidimensional, and showed that positive urgency was distinct from impulsivity-like constructs identified in 2 models of impulsive behavior. In Study 2, they showed that positive urgency explained variance in risky behavior not explained by measures of other impulsivity-like constructs, differentially explained positive mood-based risky behavior, differentiated individuals at risk for problem gambling from those not at risk, and interacted with drinking motives and expectancies as predicted to explain problem drinking behavior. In Study 3, they confirmed the hypothesis that positive urgency differentiated alcoholics from both eating-disordered and control individuals.

Electrophoretic mobility shift assay (EMSA) for detecting protein-nucleic acid interactions.

Abstract: The gel electrophoresis mobility shift assay (EMSA) is used to detect protein complexes with nucleic acids. It is the core technology underlying a wide range of qualitative and quantitative analyses for the characterization of interacting systems. In the classical assay, solutions of protein and nucleic acid are combined and the resulting mixtures are subjected to electrophoresis under native conditions through polyacrylamide or agarose gel. After electrophoresis, the distribution of species containing nucleic acid is determined, usually by autoradiography of 32P-labeled nucleic acid. In general, protein-nucleic acid complexes migrate more slowly than the corresponding free nucleic acid. In this protocol, we identify the most important factors that determine the stabilities and electrophoretic mobilities of complexes under assay conditions. A representative protocol is provided and commonly used variants are discussed. Expected outcomes are briefly described. References to extensions of the method and a troubleshooting guide are provided.

GGE Biplot vs. AMMI Analysis of Genotype-by-Environment Data

Abstract: The use of genotype main effect (G) plus genotype-by-environment (GE) interaction (G+GE) biplot analysis by plant breeders and other agricultural researchers has increased dramatically during the past 5 yr for analyzing multi-environment trial (MET) data. Recently, however, its legitimacy was questioned by a proponent of Additive Main Effect and Multiplicative Interaction (AMMI) analysis. The objectives of this review are: (i) to compare GGE biplot analysis and AMMI analysis on three aspects of genotype-by-environment data (GED) analysis, namely mega-environment analysis, genotype evaluation, and test-environment evaluation; (ii) to discuss whether G and GE should be combined or separated in these three aspects of GED analysis; and (iii) to discuss the role and importance of model diagnosis in biplot analysis of GED. Our main conclusions are: (i) both GGE biplot analysis and AMMI analysis combine rather than separate G and GE in mega-environment analysis and genotype evaluation, (ii) the GGE biplot is superior to the AMMI1 graph in mega-environment analysis and genotype evaluation because it explains more G+GE and has the inner-product property of the biplot, (iii) the discriminating power vs. representativeness view of the GGE biplot is effective in evaluating test environments, which is not possible in AMMI analysis, and (iv) model diagnosis for each dataset is useful, but accuracy gain from model diagnosis should not be overstated.

Clinical practice guideline: Adult sinusitis

Abstract: Objective This guideline provides evidence-based recommendations on managing sinusitis, defined as symptomatic inflammation of the paranasal sinuses. Sinusitis affects 1 in 7 adults in the United States, resulting in about 31 million individuals diagnosed each year. Since sinusitis almost always involves the nasal cavity, the term rhinosinusitis is preferred. The guideline target patient is aged 18 years or older with uncomplicated rhinosinusitis, evaluated in any setting in which an adult with rhinosinusitis would be identified, monitored, or managed. This guideline is intended for all clinicians who are likely to diagnose and manage adults with sinusitis. Purpose The primary purpose of this guideline is to improve diagnostic accuracy for adult rhinosinusitis, reduce inappropriate antibiotic use, reduce inappropriate use of radiographic imaging, and promote appropriate use of ancillary tests that include nasal endoscopy, computed tomography, and testing for allergy and immune function. In creating this guideline the American Academy of Otolaryngology–Head and Neck Surgery Foundation selected a panel representing the fields of allergy, emergency medicine, family medicine, health insurance, immunology, infectious disease, internal medicine, medical informatics, nursing, otolaryngology–head and neck surgery, pulmonology, and radiology. Results The panel made strong recommendations that 1) clinicians should distinguish presumed acute bacterial rhinosinusitis (ABRS) from acute rhinosinusitis caused by viral upper respiratory infections and noninfectious conditions, and a clinician should diagnose ABRS when (a) symptoms or signs of acute rhinosinusitis are present 10 days or more beyond the onset of upper respiratory symptoms, or (b) symptoms or signs of acute rhinosinusitis worsen within 10 days after an initial improvement (double worsening), and 2) the management of ABRS should include an assessment of pain, with analgesic treatment based on the severity of pain. The panel made a recommendation against radiographic imaging for patients who meet diagnostic criteria for acute rhinosinusitis, unless a complication or alternative diagnosis is suspected. The panel made recommendations that 1) if a decision is made to treat ABRS with an antibiotic agent, the clinician should prescribe amoxicillin as first-line therapy for most adults, 2) if the patient worsens or fails to improve with the initial management option by 7 days, the clinician should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications, 3) clinicians should distinguish chronic rhinosinusitis (CRS) and recurrent acute rhinosinusitis from isolated episodes of ABRS and other causes of sinonasal symptoms, 4) clinicians should assess the patient with CRS or recurrent acute rhinosinusitis for factors that modify management, such as allergic rhinitis, cystic fibrosis, immunocompromised state, ciliary dyskinesia, and anatomic variation, 5) the clinician should corroborate a diagnosis and/or investigate for underlying causes of CRS and recurrent acute rhinosinusitis, 6) the clinician should obtain computed tomography of the paranasal sinuses in diagnosing or evaluating a patient with CRS or recurrent acute rhinosinusitis, and 7) clinicians should educate/counsel patients with CRS or recurrent acute rhinosinusitis regarding control measures. The panel offered as options that 1) clinicians may prescribe symptomatic relief in managing viral rhinosinusitis, 2) clinicians may prescribe symptomatic relief in managing ABRS, 3) observation without use of antibiotics is an option for selected adults with uncomplicated ABRS who have mild illness (mild pain and temperature <38.3°C or 101°F) and assurance of follow-up, 4) the clinician may obtain nasal endoscopy in diagnosing or evaluating a patient with CRS or recurrent acute rhinosinusitis, and 5) the clinician may obtain testing for allergy and immune function in evaluating a patient with CRS or recurrent acute rhinosinusitis. Disclaimer This clinical practice guideline is not intended as a sole source of guidance for managing adults with rhinosinusitis. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.

Plate tectonics in the classification of personality disorder: shifting to a dimensional model.

Abstract: The diagnostic categories of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders were developed in the spirit of a traditional medical model that considers mental disorders to be qualitatively distinct conditions (see, e.g., American Psychiatric Association, 2000). Work is now beginning on the fifth edition of this influential diagnostic manual. It is perhaps time to consider a fundamental shift in how psychopathology is conceptualized and diagnosed. More specifically, it may be time to consider a shift to a dimensional classification of personality disorder that would help address the failures of the existing diagnostic categories as well as contribute to an integration of the psychiatric diagnostic manual with psychology's research on general personality structure.

Spatial-Depth Super Resolution for Range Images

Abstract: We present a new post-processing step to enhance the resolution of range images. Using one or two registered and potentially high-resolution color images as reference, we iteratively refine the input low-resolution range image, in terms of both its spatial resolution and depth precision. Evaluation using the Middlebury benchmark shows across-the-board improvement for sub-pixel accuracy. We also demonstrated its effectiveness for spatial resolution enhancement up to 100 times with a single reference image.

Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide

Abstract: Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians.

Abstract: Background and Overview Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to reduce cardiac events after coronary stenting. However, many patients and health care providers prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis, myocardial infarction and death. Conclusions and Clinical Implications This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent and educating patients and health care providers about hazards of premature discontinuation. It also recommends postponing elective surgery for one year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents.

Sense of Belonging in College Freshmen at the Classroom and Campus Levels.

Abstract: The importance of students' sense of school belonging for many adaptive outcomes is becoming well established; however, few researchers have focused on college-aged populations. In this study, the authors examined associations between undergraduate students' sense of class belonging and their academic motivation in that class, their sense of class belonging and perceptions of their instructors' characteristics, and their class and campus-level sense of belonging. They distributed questionnaires to students at a southeastern university; freshmen (N = 238) completed the questionnaire. The authors found associations between (a) students' sense of class belonging and their academic self-efficacy, intrinsic motivation, and task value; (b) students' sense of class-level belonging and their perceptions of instructors' warmth and openness, encouragement of student participation, and organization; and (c) students' sense of university-level belonging and their sense of social acceptance. The authors found smaller ...

Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment

Abstract: Objective: To evaluate the total number of synapses in the stratum radiatum (str rad) of the human hippocampal CA1 subfield in individuals with mild Alzheimer disease (mAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI) and determine if synapse loss is an early event in the progression of the disease. Methods: Short postmortem autopsy tissue was obtained, and an unbiased stereologic sampling scheme coupled with transmission electron microscopy was used to directly visualize synaptic contacts. Results: Individuals with mAD had fewer synapses (55%) than the other two diagnostic groups. Individuals with MCI had a mean synaptic value that was 18% lower than the NCI group mean. The total number of synapses showed a correlation with several cognitive tests including those involving both immediate and delayed recall. Total synaptic numbers showed no relationship to the subject9s Braak stage or to APOE genotype. The volume of the str rad was reduced in mAD vs the other two diagnostic groups that were not different from each other. Conclusion: These results strongly support the concept that synapse loss is a structural correlate involved very early in cognitive decline in mild Alzheimer disease (mAD) and supports mild cognitive impairment as a transitional stage between mAD and no cognitive impairment.

Aggression and Antisocial Behavior in Youth

Abstract: This chapter reviews the literatures on the normative development of antisocial behavior and how individual differences in antisocial behavior develop across the life span. The literature can be integrated with a model that includes biological (genetic, neural, and temperament) and socialization (parenting, peer, academic, and neighborhood) factors in antisocial development. These factors operate as main effects that cumulate, interaction effects that moderate each other, and developmental processes that mediate each other and transact across time. Social information processing factors (e.g., selective attention, hostile attributional bias, incompetent social problem-solving skills, and response evaluation biases) have been found to mediate these effects. Interventions that address these factors have proven partially successful in preventing antisocial development and may be targets for future efforts. Keywords: biological factors; individual differences; intervention; normative development; social information processing; socialization factors

TP53 mutations and survival in squamous-cell carcinoma of the head and neck.

Abstract: Background The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck. Methods A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53–DNA complexes. TP53 mutational status was compared with clinical outcome. Results TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-...

The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development

Abstract: Skeletal development and turnover occur in close spatial and temporal association with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen tension and respond to hypoxia by activating the hypoxia-inducible factor alpha (HIF alpha) pathway. Here we provide evidence that HIF alpha promotes angiogenesis and osteogenesis by elevating VEGF levels in osteoblasts. Mice overexpressing HIF alpha in osteoblasts through selective deletion of the von Hippel-Lindau gene (Vhl) expressed high levels of Vegf and developed extremely dense, heavily vascularized long bones. By contrast, mice lacking Hif1a in osteoblasts had the reverse skeletal phenotype of that of the Vhl mutants: long bones were significantly thinner and less vascularized than those of controls. Loss of Vhl in osteoblasts increased endothelial sprouting from the embryonic metatarsals in vitro but had little effect on osteoblast function in the absence of blood vessels. Mice lacking both Vhl and Hif1a had a bone phenotype intermediate between those of the single mutants, suggesting overlapping functions of HIFs in bone. These studies suggest that activation of the HIF alpha pathway in developing bone increases bone modeling events through cell-nonautonomous mechanisms to coordinate the timing, direction, and degree of new blood vessel formation in bone.

Framework-catenation isomerism in metal-organic frameworks and its impact on hydrogen uptake.

Abstract: A strategy to control framework-catenation in MOFs has been presented; contributions to hydrogen uptake from interpenetration and unsaturated metal centers have been resolved.

Evolution on ecological time‐scales

Abstract: Summary 1Ecologically significant evolutionary change, occurring over tens of generations or fewer, is now widely documented in nature. These findings counter the long-standing assumption that ecological and evolutionary processes occur on different time-scales, and thus that the study of ecological processes can safely assume evolutionary stasis. Recognition that substantial evolution occurs on ecological time-scales dissolves this dichotomy and provides new opportunities for integrative approaches to pressing questions in many fields of biology. 2The goals of this special feature are twofold: to consider the factors that influence evolution on ecological time-scales – phenotypic plasticity, maternal effects, sexual selection, and gene flow – and to assess the consequences of such evolution – for population persistence, speciation, community dynamics, and ecosystem function. 3The role of evolution in ecological processes is expected to be largest for traits that change most quickly and for traits that most strongly influence ecological interactions. Understanding this fine-scale interplay of ecological and evolutionary factors will require a new class of eco-evolutionary dynamic modelling. 4Contemporary evolution occurs in a wide diversity of ecological contexts, but appears to be especially common in response to anthropogenic changes in selection and population structure. Evolutionary biology may thus offer substantial insight to many conservation issues arising from global change. 5Recent studies suggest that fluctuating selection and associated periods of contemporary evolution are the norm rather than exception throughout the history of life on earth. The consequences of contemporary evolution for population dynamics and ecological interactions are likely ubiquitous in time and space.

Metabolic changes in pregnancy.

Abstract: Maternal metabolism changes substantially during pregnancy. Early gestation can be viewed as an anabolic state in the mother with an increase in maternal fat stores and small increases in insulin sensitivity. Hence, nutrients are stored in early pregnancy to meet the feto-placental and maternal demands of late gestation and lactation. In contrast, late pregnancy is better characterized as a catabolic state with decreased insulin sensitivity (increased insulin resistance). An increase in insulin resistance results in increases in maternal glucose and free fatty acid concentrations, allowing for greater substrate availability for fetal growth.

On the validity and utility of discriminating among impulsivity-like traits.

Abstract: The ability to make precise distinctions among related personality constructs helps clarify theory and increases the utility of clinical assessment. In three studies, the authors evaluated the validity of distinctions among four impulsivity-like traits: sensation seeking, lack of planning, lack of persistence, and urgency (acting rashly when distressed). Factor analyses indicated that lack of planning and lack of persistence are two distinct facets of one broader trait, whereas urgency and sensation seeking are both very modestly related to each other and to the planning/persistence measures. The authors developed interview assessments of each, and multitrait, multimethod matrix results indicated clear convergent and discriminant validity among the constructs. The distinctions among them were useful: The traits accounted for different aspects of risky behaviors. Sensation seeking appeared to relate to the frequency of engaging in risky behaviors, and urgency appeared to relate to problem levels of involve...

Heart Rate Variability Reflects Self-Regulatory Strength, Effort, and Fatigue

Abstract: Experimental research reliably demonstrates that self-regulatory deficits are a consequence of prior self-regulatory effort. However, in naturalistic settings, although people know that they are sometimes vulnerable to saying, eating, or doing the wrong thing, they cannot accurately gauge their capacity to self-regulate at any given time. Because self-regulation and autonomic regulation colocalize in the brain, an autonomic measure, heart rate variability (HRV), could provide an index of self-regulatory strength and activity. During an experimental manipulation of self-regulation (eating carrots or cookies), HRV was elevated during high self-regulatory effort (eat carrots, resist cookies) compared with low self-regulatory effort (eat cookies, resist carrots). The experimental manipulation and higher HRV at baseline independently predicted persistence at a subsequent anagram task. HRV appears to index self-regulatory strength and effort, making it possible to study these phenomena in the field as well as the lab.

Aging of the Somatosensory System: A Translational Perspective

Abstract: Balance in the elderly population is a major concern given the often catastrophic and disabling consequences of fall-related injuries. Structural and functional declines of the somatosensory system occur with aging and potentially contribute to postural instability in older adults. The objectives of this article are: (1) to discuss the evidence regarding age-related anatomical and physiological changes that occur in the peripheral proprioceptive and cutaneous systems, (2) to relate the basic science research to the current evidence regarding clinical changes associated with normal aging, and (3) to review the evidence regarding age-related proprioceptive and cutaneous clinical changes and relate it to research examining balance performance in older adults. The article is organized by an examination of the receptors responsible for activating afferent pathways (muscle spindle, golgi tendon organ, and articular and cutaneous receptors) and the corresponding sensory afferent fibers and neurons. It integrates basic science laboratory findings with clinical evidence suggesting that advanced aging results in a decline in cutaneous sensation and proprioception. The potential relationship between postural instability and sensory impairments in older adults also is discussed. Current laboratory and clinical evidence suggests that aging results in: (1) diverse and nonuniform declines in the morphology and physiological function of the various sensory structures examined, (2) preferential loss of distal large myelinated sensory fibers and receptors, and (3) impaired distal lower-extremity proprioception, vibration and discriminative touch, and balance. These findings provide foundational knowledge that emphasizes the importance of using reliable and valid sensory testing protocols for older adults and the need for further research that clarifies the relationship between sensory impairment and balance.

The National Alzheimer's Coordinating Center (NACC) database: the Uniform Data Set.

Abstract: The National Alzheimer's Coordinating Center (NACC) is responsible for developing and maintaining a database of participant information collected from the 29 Alzheimer's Disease Centers (ADCs) funded by the National Institute on Aging (NIA). The NIA appointed the ADC Clinical Task Force to determine and define an expanded, standardized clinical data set, called the Uniform Data Set (UDS). The goal of the UDS is to provide ADC researchers a standard set of assessment procedures, collected longitudinally, to better characterize ADC participants with mild Alzheimer disease and mild cognitive impairment in comparison with nondemented controls. NACC implemented the UDS (September 2005) by developing data collection forms for initial and follow-up visits based on Clinical Task Force definitions, a relational database, and a data submission system accessible by all ADCs. The NIA requires ADCs to submit UDS data to NACC for all their Clinical Core participants. Thus, the NACC web site (https://www.alz.washington.edu) was enhanced to provide efficient and secure access data submission and retrieval systems.

Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation

Abstract: Circadian rhythms of cell and organismal physiology are controlled by an autoregulatory transcription-translation feedback loop that regulates the expression of rhythmic genes in a tissue-specific manner. Recent studies have suggested that components of the circadian pacemaker, such as the Clock and Per2 gene products, regulate a wide variety of processes, including obesity, sensitization to cocaine, cancer susceptibility, and morbidity to chemotherapeutic agents. To identify a more complete cohort of genes that are transcriptionally regulated by CLOCK and/or circadian rhythms, we used a DNA array interrogating the mouse protein-encoding transcriptome to measure gene expression in liver and skeletal muscle from WT and Clock mutant mice. In WT tissue, we found that a large percentage of expressed genes were transcription factors that were rhythmic in either muscle or liver, but not in both, suggesting that tissue-specific output of the pacemaker is regulated in part by a transcriptional cascade. In comparing tissues from WT and Clock mutant mice, we found that the Clock mutation affects the expression of many genes that are rhythmic in WT tissue, but also profoundly affects many nonrhythmic genes. In both liver and skeletal muscle, a significant number of CLOCK-regulated genes were associated with the cell cycle and cell proliferation. To determine whether the observed patterns in cell-cycle gene expression in Clock mutants resulted in functional dysregulation, we compared proliferation rates of fibroblasts derived from WT or Clock mutant embryos and found that the Clock mutation significantly inhibits cell growth and proliferation.