Sample records for early lifestage diseases

  1. EARLY LIFESTAGE EFFECTS OF PAH PHOTOACTIVATED TOXICITY IN MEDAKA (ORYZIAS LATIPES)

    EPA Science Inventory

    Two critical questions have yet to be sufficiently addressed for risk assessments of photoactived PAH toxicity to be completed. These include standrdized methods for quantifying the dose of activating radiation received by target organisms, and the potential for early lifestage e...

  2. Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

    EPA Science Inventory

    Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

  3. Chromium Toxicity Test for Fall Chinook Salmon (Oncorhynchus tshawytscha) Using Hanford Site Groundwater: Onsite Early Life-Stage Toxicity Evaluation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patton, Gregory W; Dauble, Dennis D; Chamness, Mickie A

    The objective of this study was to evaluate site-specific effects for early life-stage (eyed eggs to free swimming juveniles) fall chinook salmon that might be exposed to hexavalent chromium from Hanford groundwater sources. Our exposure conditions included hexavalent chromium obtained from Hanford groundwater wells near the Columbia River, Columbia River water as the diluent, and locally adapted populations of fall chinook salmon. This report describes both a 96-hr pretest using rainbow trout eggs and an early life-stage test beginning with chinook salmon eggs.

  4. Ocean Acidification Effects on the Early Life-Stages of Commercially Important Flatfish of the Northeast USA

    NASA Astrophysics Data System (ADS)

    Chambers, R. C.; Habeck, E. A.; Candelmo, A. C.; Poach, M.; Wieczorek, D.; Phelan, B.; Caldarone, E.; Cooper, K. R.

    2012-12-01

    The limited available evidence about effects on finfish of high CO2 levels and acidification of our oceans suggests that effects will differ across fish species, be subtle, and interact with other stressors. A carefully planned, experimental framework was developed to cast an extensive yet strategic inferential net. Three key elements of our approach are the use of 1) multiple marine finfish species of relevance to the northeastern USA that differ in their ecologies including spawning season and habitat of early life-stages; 2) a wide yet realistic range of environmental conditions (i.e., concurrent manipulation of CO2 levels and water temperatures), and 3) a diverse set of response variables related to fish sensitivity to elevated CO2 levels, water temperatures, and their interactions. The response variable set reflects fish condition, fitness, and likelihood of recruitment, and includes measures of viability, physiology, histopathology, growth, development, and behavior expressed during fish early life-stages (i.e., gametes, embryos, and larvae). Early life-stages were chosen due to the anticipation of their vulnerability to acid-base challenges in their environment. To date, factorial experiments have been implemented on summer flounder (Paralichthys dentatus) and winter flounder (Pseudopleuronectes americanus). Initial results reveal survival of summer flounder embryos is compromised by pH < 7.7 (CO2 > 790 ppm). These results were similar across offspring groups (i.e., embryos from different parents). Winter flounder are larger at hatching when exposed to high CO2 levels in the coolest environment implemented in our experiments (range 4 to 10 ○C). Further responses of advanced larvae of both flounder species are currently being assessed for evidence of other whole body, component organ, and biochemical impairment. This study will aid researchers and resource managers in identifying species types, life-stages, and biotic responses that are most sensitive to

  5. Discovering and annotating fish early life-stage (FELS) adverse outcome pathways: Putting the research strategy into practice

    EPA Science Inventory

    In May 2012, a HESI-sponsored expert workshop yielded a proposed research strategy for systematically discovering, characterizing, and annotating fish early life-stage (FELS) adverse outcome pathways (AOPs) as well as prioritizing AOP development in light of current restrictions ...

  6. Investigating Alternatives to the Fish Early Life-Stage Test: A Strategy for Discovering and Annotating Adverse Outcome Pathways for Early Fish Development

    EPA Science Inventory

    The fish early life-stage (FELS) test (OECD Test Guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an on-going effort to develop efficient and cost-effec...

  7. Development of an alternative testing strategy for the fish early life-stage (FELS) test using the AOP framework

    EPA Science Inventory

    Currently, the fish early life-stage (FELS) test (OECD 210) is the primary guideline used to estimate chronic toxicity of regulated chemicals. Although already more cost-efficient than adult fish tests, the FELS test has some important drawbacks. Both industry and regulatory inst...

  8. Effects of tributyltin on early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes).

    PubMed

    Horie, Yoshifumi; Yamagishi, Takahiro; Shintaku, Yoko; Iguchi, Taisen; Tatarazako, Norihisa

    2018-07-01

    Tributyltin, an organotin compound, was used worldwide as an antifouling agent in aquatic environments and there has been much concern about the toxicological and ecotoxicological properties of organotin compounds. Even though it has been prohibited worldwide, tributyltin is still detected at low concentrations in aquatic environments. Here we investigated the effects of tributyltin on the early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes). In adults, exposure to tributyltin at 3.82 μg/L suppressed fecundity and fertility and increased mortality. At 10.48 μg/L all medaka died by the sixth day of exposure. Exposure to tributyltin during early life-stages induced no significant differences in mortality or embryonic development, but growth was suppressed in groups exposed to 0.13 and 0.68 μg/L. Furthermore, there was no abnormal gonadal development in Japanese medaka exposed to tributyltin. These results provide evidence of the negative effects of tributyltin on reproduction in a teleost fish. Tributyltin did not affect gonadal sex differentiation in Japanese medaka, but fecundity and fertility were suppressed, although it is not clear whether this suppression resulted from the endocrine-disrupting action of tributyltin or its toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Life-stage, not climate change, explains observed tree range shifts

    PubMed Central

    Máliš, František; Kopecký, Martin; Petřík, Petr; Vladovič, Jozef; Merganič, Ján; Vida, Tomáš

    2017-01-01

    Ongoing climate change is expected to shift tree species distribution and therefore affect forest biodiversity and ecosystem services. To assess and project tree distributional shifts, researchers may compare the distribution of juvenile and adult trees under the assumption that differences between tree life-stages reflect distributional shifts triggered by climate change. However, the distribution of tree life-stages could differ within the lifespan of trees, therefore we hypothesize that currently observed distributional differences could represent shifts over ontogeny as opposed to climatically driven changes. Here we test this hypothesis with data from 1435 plots resurveyed after more than three decades across the Western Carpathians. We compared seedling, sapling and adult distribution of 12 tree species along elevation, temperature and precipitation gradients. We analyzed i) temporal shifts between the surveys and ii) distributional differences between tree life-stages within both surveys. Despite climate warming, tree species distribution of any life-stage did not shift directionally upward along elevation between the surveys. Temporal elevational shifts were species-specific and an order of magnitude lower than differences among tree life-stages within the surveys. Our results show that the observed range shifts among tree life-stages are more consistent with ontogenetic differences in the species’ environmental requirements than with responses to recent climate change. The distribution of seedlings substantially differed from saplings and adults, while the distribution of saplings did not differ from adults, indicating a critical transition between seedling and sapling tree life-stages. Future research has to take ontogenetic differences among life-stages into account as we found that distributional differences recently observed worldwide may not reflect climate change but rather the different environmental requirements of tree life-stages. PMID:26725258

  10. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) ...

    EPA Pesticide Factsheets

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. Adverse outcome pathways (AOPs), in this case endocrine disruption during development, provide a biologically-based framework for linking molecular initiating events triggered by chemical exposures to key events leading to adverse outcomes. The application of AOPs to human health risk assessment requires extrapolation of in vitro HTS toxicity data to in vivo exposures (IVIVE) in humans, which can be achieved through the use of a PBPK/PD model. Exposure scenarios for chemicals in the PBPK/PD model will consider both placental and lactational transfer of chemicals, with a focus on age dependent dosimetry during fetal development and after birth for a nursing infant. This talk proposes a universal life-stage computational model that incorporates changing physiological parameters to link environmental exposures to in vitro levels of HTS assays related to a developmental toxicological AOP for vascular disruption. In vitro toxicity endpoints discussed are based on two mechanisms: 1) Fetal vascular disruption, and 2) Neurodevelopmental toxicity induced by altering thyroid hormone levels in neonates via inhibition of thyroperoxidase in the thyroid gland. Application of our Life-stage computati

  11. Ocean acidification effects in the early life-stages of summer flounder, Paralichthys dentatus

    NASA Astrophysics Data System (ADS)

    Chambers, R. C.; Candelmo, A. C.; Habeck, E. A.; Poach, M. E.; Wieczorek, D.; Cooper, K. R.; Greenfield, C. E.; Phelan, B. A.

    2013-08-01

    -facial features were affected by CO2 levels that changed with ages of larvae. Skeletal elements of larvae from ambient CO2 environments were comparable or smaller than those from elevated CO2 environments when younger (14 d and 21 d post-hatching) but larger at older ages (28 d). The degree of impairment in the early life-stages of summer flounder due to elevated CO2 levels suggests that this species will be challenged by ocean acidification in the near future. Further experimental comparative studies on marine fish are warranted in order to identify the species, life-stages, ecologies, and responses that are most sensitive to increased levels of CO2 and acidity in near-future ocean waters, and a strategy is proposed for achieving these goals.

  12. Innovative curriculum: Integrating the bio-behavioral and social science principles across the LifeStages in basic science years.

    PubMed

    Lele Mookerjee, Anuradha; Fischer, Bradford D; Cavanaugh, Susan; Rajput, Vijay

    2018-05-20

    Behavioral and social science integration in clinical practice improves health outcomes across the life stages. The medical school curriculum requires an integration of the behavioral and social science principles in early medical education. We developed and delivered a four-week course entitled "LifeStages" to the first year medical students. The learning objectives of the bio-behavioral and social science principles along with the cultural, economic, political, and ethical parameters were integrated across the lifespan in the curriculum matrix. We focused on the following major domains: Growth and Brain Development; Sexuality, Hormones and Gender; Sleep; Cognitive and Emotional Development; Mobility, Exercise, Injury and Safety; Nutrition, Diet and Lifestyle; Stress and coping skills, Domestic Violence; Substance Use Disorders; Pain, Illness and Suffering; End of Life, Ethics and Death along with Intergenerational issues and Family Dynamics. Collaboration from the clinical and biomedical science departments led to the dynamic delivery of the course learning objectives and content. The faculty developed and led a scholarly discussion, using the case of a multi-racial, multi-generational family during Active Learning Group (ALG) sessions. The assessment in the LifeStages course involved multiple assessment tools: including the holistic assessment by the faculty facilitator inside ALGs, a Team-Based Learning (TBL) exercise, multiple choice questions and Team Work Assessment during which the students had to create a clinical case on a LifeStages domain along with the facilitators guide and learning objectives.

  13. Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards

    EPA Science Inventory

    A Life-stage Physiologically-Based Pharmacokinetic (PBPK) model was developed to include descriptions of several life-stage events such as pregnancy, fetal development, the neonate and child growth. The overall modeling strategy was used for in vitro to in vivo (IVIVE) extrapolat...

  14. Early Life Stages

    EPA Pesticide Factsheets

    Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

  15. Species-environment relationships and vegetation patterns: Effects of spatial scale and tree life-stage

    USGS Publications Warehouse

    Stohlgren, T.J.; Bachand, R.R.; Onami, Y.; Binkley, Dan

    1998-01-01

    Do relationships between species and environmental gradients strengthen or weaken with tree life-stage (i.e., small seedlings, large seedlings, saplings, and mature trees)? Strengthened relationships may lead to distinct forest type boundaries, or weakening connections could lead to gradual ecotones and heterogeneous forest landscapes. We quantified the changes in forest dominance (basal area of tree species by life-stage) and environmental factors (elevation, slope, aspect, intercepted photosynthetically active radiation (PAR), summer soil moisture, and soil depth and texture) across 14 forest ecotones (n = 584, 10 m x 10 m plots) in Rocky Mountain National Park, Colorado, U.S.A. Local, ecotone-specific species-environment relationships, based on multiple regression techniques, generally strengthened from the small seedling stage (multiple R2 ranged from 0.00 to 0.26) to the tree stage (multiple R2 ranged from 0.20 to 0.61). At the landscape scale, combined canonical correspondence analysis (CCA) among species and for all tree life-stages suggested that the seedlings of most species became established in lower-elevation, drier sites than where mature trees of the same species dominated. However, conflicting evidence showed that species-environment relationships may weaken with tree life-stage. Seedlings were only found in a subset of plots (habitats) occupied by mature trees of the same species. At the landscape scale, CCA results showed that species-environment relationships weakened somewhat from the small seedling stage (86.4% of the variance explained by the first two axes) to the tree stage (76.6% of variance explained). The basal area of tree species co-occurring with Pinus contorta Doug. ex. Loud declined more gradually than P. contorta basal area declined across ecotones, resulting in less-distinct forest type boundaries. We conclude that broad, gradual ecotones and heterogeneous forest landscapes are created and maintained by: (1) sporadic establishment

  16. Black-White Disparity in Young Adults' Disease Risk: An Investigation of Variation in the Vulnerability of Black Young Adults to Early and Later Adversity.

    PubMed

    Wickrama, Kandauda A S; Bae, Dayoung; O'Neal, Catherine Walker

    2016-08-01

    Socioeconomic adversity in early years and young adulthood are risk factors for poor health in young adulthood. Population differences in exposure to stressful socioeconomic conditions partly explain the higher prevalence of disease among black young adults. Another plausible mechanism is that blacks are differentially vulnerable to socioeconomic adversity (differential vulnerability hypothesis), which has not been adequately investigated in previous research. The present study investigated variation in the vulnerability of black young adults leading to cardiometabolic (CM) disease risk. We used a nationally representative sample of 8,824 adolescents who participated in the Add Health study. Early and later adversity was measured using a cumulative index of social and material adversity in adolescence and young adulthood. CM disease risk was assessed using nine biomarkers. Path analysis within a structural equation modeling framework was used. The findings indicated that both early and later socioeconomic adversity act as stressors with independent additive influences on young adults' CM disease risk, consistent with the differential exposure hypothesis. Moreover, the results showed that black youth are less vulnerable to early socioeconomic adversity than whites, but they are more vulnerable to later adversity. The findings provide support for the unique and additive influences of early and later socioeconomic adversity on CM disease risk contributing to the black-white health disparity in young adulthood. The results also suggest that vulnerability to adversity varies depending on the life stage, which highlights the need for life-stage specific interventions to mitigate the existing black-white disparity in young adults' physical health. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  17. Etiology of Early Lifestage Diseases, Project 84-44, 1985 Final Report.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sauter, R.W.

    1986-10-01

    Each year hatcheries experience loss of eggs, fry and fingerlings due to a group of poorly defined diseases called White Spot and Coagulated Yolk. Samples of maternal blood and ovarian fluid (coelomic fluid), as well as unfertilized eggs, were collected at spawning and subsequently tested for the presence of bacteria. Our tests reveal that there is a wide range in mortality rates experienced by the progeny of different brood salmon. Microbiologic tests revealed that these eggs contained a variety of both Gram positive and Gram negative bacteria within their yolk and that the fluids from the females who produced thesemore » lots were contaminated with a variety of bacteria. In contrast the eggs and maternal fluids from the six egg lots which experienced the lowest mortalities did not contain high numbers of Gram positive bacteria and contributed only 5% of the total mortalities observed within the 30 egg lots tested. From the 60 egg lots tested over two brood years we have isolated 18 different bacterial genera containing 32 different species from within the yolk surface sterilized, unfertilized eggs. Our tests suggest that Aeromonas hydrophila, Pseudomonas (3 species) Staphylococcus aureus, Vibrio sp., Corynebacterium hoffmanii, Listeria sp. and Bacillus sp. when detected within the yolk of eggs sampled from egg lots prior to fertilization will be associated with higher than normal mortality rates when the remainder of the egg lots containing these bacteria are incubated and reared. 36 refs., 16 figs.« less

  18. EVALUATION OF BIOACCUMULATION AND PHOTOINDUCED TOXICITY OF FLUORANTHENE IN LARVAL AND ADULT LIFE-STAGES OF CHIRONOMUS TENTANS

    EPA Science Inventory

    Laboratory sediment tests were conducted to evaluate the bioaccumulation and photoinduced toxicity of fluoranthene in larval and adult life-stages of Chironomus tentans. In the first of two experiments, fourth-instar and adult C. tentans exposed to spiked sediments were collected...

  19. Evaluation of Endocrine Effects in Birds: A Case for a Targeted, Life-stage and Endpoint Specific Approach

    EPA Science Inventory

    The EFSA "Scientific Opinion on the Science Behind the Guidance" document on risk assessment for birds and mammals has a chapter on risk assessment of substances with endocrine-disrupting properties in birds. It discusses that targeted partial life-cycle or critical life-stage te...

  20. A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

    PubMed

    Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

    2014-08-01

    Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Treatment of early Parkinson's disease.

    PubMed

    Pahwa, Rajesh; Lyons, Kelly E

    2014-08-01

    This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

  2. Utilizing ToxCast Data and Lifestage Physiologically-Based Pharmacokinetic (PBPK) models to Drive Adverse Outcome Pathways (AOPs)-Based Margin of Exposures (ABME) to Chemicals.

    EPA Science Inventory

    Utilizing ToxCast Data and Lifestage Physiologically-Based Pharmacokinetic (PBPK) models to Drive Adverse Outcome Pathways (AOPs)-Based Margin of Exposures (ABME) to Chemicals. Hisham A. El-Masri1, Nicole C. Klienstreur2, Linda Adams1, Tamara Tal1, Stephanie Padilla1, Kristin I...

  3. Fetal Origins of Life Stage Disease: A Zebrafish Model for the ...

    EPA Pesticide Factsheets

    In the U.S., childhood obesity has more than doubled in children and quadrupled in adolescents in the past 30 years, affects 35% of adults, and costs the U.S. healthcare industry >$200 billion annually. The chemical environment in the womb may cause susceptibility to different life-stage and life-long metabolic diseases including obesity. The challenge is to understand if exposures during developmentally sensitive windows impact life-stage disease, such as obesity, by increasing adipose tissue mass. In vitro models lack the integrated systems approach needed to assess adipose development, while mammalian models are impractical in a screen of thousands of chemicals. Therefore, an obesogen screening method was developed to interrogate bioactivity using a full systems approach, in a vertebrate zebrafish model with complete metabolic activity, at a time when the full signaling repertoire is expressed and active, to optimally examine how chemical dose and duration impact life-stage adipose mass. A time-line for adipose depot formation was mapped in zebrafish 6−14 days post fertilization (dpf) using the lipophilic dye, Nile Red, in combination with fluorescent microscopy. Those time points were then used to investigate the impact of embryonic tributyltin chloride (TBT, a known obesogen) exposure (10nM daily renewal, 0−5dpf) on adipose mass. Fluorescent microscopy revealed adipose depots that were larger and appeared 2 days earlier in TBT treated compared to contro

  4. Four Models Including Fish, Seafood, Red Meat and Enriched Foods to Achieve Australian Dietary Recommendations for n-3 LCPUFA for All Life-Stages

    PubMed Central

    Fayet-Moore, Flavia; Baghurst, Katrine; Meyer, Barbara J.

    2015-01-01

    Populations are not meeting recommended intakes of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). The aim was (i) to develop a database on n-3 LCPUFA enriched products; (ii) to undertake dietary modelling exercise using four dietary approaches to meet the recommendations and (iii) to determine the cost of the models. Six n-3 LCPUFA enriched foods were identified. Fish was categorised by n-3 LCPUFA content (mg/100 g categories as “excellent” “good” and “moderate”). The four models to meet recommended n-3 LCPUFA intakes were (i) fish only; (ii) moderate fish (with red meat and enriched foods); (iii) fish avoiders (red meat and enriched foods only); and (iv) lacto-ovo vegetarian diet (enriched foods only). Diets were modelled using the NUTTAB2010 database and n-3 LCPUFA were calculated and compared to the Suggested Dietary Targets (SDT). The cost of meeting these recommendations was calculated per 100 mg n-3 LCPUFA. The SDT were achieved for all life-stages with all four models. The weekly food intake in number of serves to meet the n-3 LCPUFA SDT for all life-stages for each dietary model were: (i) 2 “excellent” fish; (ii) 1 “excellent” and 1 “good” fish, and depending on life-stage, 3–4 lean red meat, 0–2 eggs and 3–26 enriched foods; (iii) 4 lean red meat, and 20–59 enriched foods; (iv) 37–66 enriched foods. Recommended intakes of n-3 LCPUFA were easily met by the consumption of fish, which was the cheapest source of n-3 LCPUFA. Other strategies may be required to achieve the recommendations including modifying the current food supply through feeding practices, novel plant sources and more enriched foods. PMID:26492269

  5. Buffering and Amplifying Interactions among OAW (Ocean Acidification & Warming) and Nutrient Enrichment on Early Life-Stage Fucus vesiculosus L. (Phaeophyceae) and Their Carry Over Effects to Hypoxia Impact.

    PubMed

    Al-Janabi, Balsam; Kruse, Inken; Graiff, Angelika; Winde, Vera; Lenz, Mark; Wahl, Martin

    2016-01-01

    Ocean acidification and warming (OAW) are occurring globally. Additionally, at a more local scale the spreading of hypoxic conditions is promoted by eutrophication and warming. In the semi-enclosed brackish Baltic Sea, occasional upwelling in late summer and autumn may expose even shallow-water communities including the macroalga Fucus vesiculosus to particularly acidified, nutrient-rich and oxygen-poor water bodies. During summer 2014 (July-September) sibling groups of early life-stage F. vesiculosus were exposed to OAW in the presence and absence of enhanced nutrient levels and, subsequently to a single upwelling event in a near-natural scenario which included all environmental fluctuations in the Kiel Fjord, southwestern Baltic Sea, Germany (54°27 ´N, 10°11 ´W). We strove to elucidate the single and combined impacts of these potential stressors, and how stress sensitivity varies among genetically different sibling groups. Enhanced by a circumstantial natural heat wave, warming and acidification increased mortalities and reduced growth in F. vesiculosus germlings. This impact, however, was mitigated by enhanced nutrient conditions. Survival under OAW conditions strongly varied among sibling groups hinting at a substantial adaptive potential of the natural Fucus populations in the Western Baltic. A three-day experimental upwelling caused severe mortality of Fucus germlings, which was substantially more severe in those sibling groups which previously had been exposed to OAW. Our results show that global (OAW), regional (nutrient enrichment) and local pressures (upwelling), both alone and co-occurring may have synergistic and antagonistic effects on survival and/or growth of Fucus germlings. This result emphasizes the need to consider combined stress effects.

  6. The role of dissolved organic carbon concentration and composition on nickel toxicity to early life-stages of the blue mussel Mytilus edulis and purple sea urchin Strongylocentrotus purpuratus.

    PubMed

    Blewett, Tamzin A; Dow, Elissa M; Wood, Chris M; McGeer, James C; Smith, D Scott

    2018-05-24

    Nickel (Ni) emissions resulting from production and transportation raise concerns about the impact of Ni exposure to marine ecosystems. Ni bioavailability models are established for FW systems, but the influence of chemical parameters (e.g. dissolved organic carbon (DOC)) on Ni toxicity within marine systems is less well understood. To examine the effects of DOC concentration and composition on Ni toxicity, acute toxicity tests were conducted on early life-stages of blue mussels (Mytilus edulis) and sea urchin embryos (Strongylocentrotus purpuratus) in full strength sea water (32 ppt). Nine different field collected samples of water with varying concentration (up to 4.5 mg C/L) and composition of DOC were collected from the east coast of the United States. Organic matter compositional analysis included molecular fluorescence and absorbance spectroscopy. The different DOC sources had different protective effects against embryo toxicity. The control (no DOC) Ni 48 h-EC 50 for Mytilus embryos was 133 µg/L (95% confidence interval (C.I.) of 123-144 µg/L), while Strongylocentrotus embryos displayed control 96-h EC 50 values of 207 µg/L (167-247 µg/L). The most significantly protective sample had high humic acid concentrations (as determined from fluorescence spectroscopy), which yielded an EC 50 of 195 µg/L (169-222 µg/L) for Mytilus, and an EC 50 of 394 µg/L (369-419 µg/L) for S. purpuratus. Among all samples, protection was related to both DOC quantity and quality, with fluorescence-resolved humic and fulvic acid concentrations showing the strongest correlations with protection for both species. These data suggest that DOC is protective against Ni toxicity in M. edulis and S. purpuratus, and that accounting for a DOC quality factor will improve predictive toxicity models such as the biotic ligand model. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Kidney Disease: Early Detection and Treatment

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Kidney Disease: Early Detection and Treatment Past Issues / Winter ... called a "urine albumin-to-creatinine ratio." Treating Kidney Disease Kidney disease is usually a progressive disease, ...

  8. Risk of early surgery for Crohn's disease: implications for early treatment strategies.

    PubMed

    Sands, Bruce E; Arsenault, Joanne E; Rosen, Michael J; Alsahli, Mazen; Bailen, Laurence; Banks, Peter; Bensen, Steven; Bousvaros, Athos; Cave, David; Cooley, Jeffrey S; Cooper, Herbert L; Edwards, Susan T; Farrell, Richard J; Griffin, Michael J; Hay, David W; John, Alex; Lidofsky, Sheldon; Olans, Lori B; Peppercorn, Mark A; Rothstein, Richard I; Roy, Michael A; Saletta, Michael J; Shah, Samir A; Warner, Andrew S; Wolf, Jacqueline L; Vecchio, James; Winter, Harland S; Zawacki, John K

    2003-12-01

    In this study we aimed to define the rate of early surgery for Crohn's disease and to identify risk factors associated with early surgery as a basis for subsequent studies of early intervention in Crohn's disease. We assembled a retrospective cohort of patients with Crohn's disease diagnosed between 1991 and 1997 and followed for at least 3 yr, who were identified in 16 community and referral-based practices in New England. Chart review was performed for each patient. Details of baseline demographic and disease features were recorded. Surgical history including date of surgery, indication, and procedure were also noted. Risk factors for early surgery (defined as major surgery for Crohn's disease within 3 yr of diagnosis, exclusive of major surgery at time of diagnosis) were identified by univariate analysis. Multiple logistic regression was used to identify independent risk factors. Of 345 eligible patients, 69 (20.1%) required surgery within 3 yr of diagnosis, excluding the 14 patients (4.1%) who had major surgery at the time of diagnosis. Overall, the interval between diagnosis and surgery was short; one half of all patients who required surgery underwent operation within 6 months of diagnosis. Risk factors identified by univariate analysis as significantly associated with early surgery included the following: smoking; disease of small bowel without colonic involvement; nausea and vomiting or abdominal pain on presentation; neutrophil count; and steroid use in the first 6 months. Disease localized to the colon only, blood in the stool, use of 5-aminosalicylate, and lymphocyte count were inversely associated with risk of early surgery. Logistic regression confirmed independent associations with smoking as a positive risk factor and involvement of colon without small bowel as a negative risk factor for early surgery. The rate of surgery is high in the first 3 yr after diagnosis of Crohn's disease, particularly in the first 6 months. These results suggest that

  9. Unusual early-onset Huntingtons disease.

    PubMed

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  10. Early diagnosis of Parkinson's disease.

    PubMed

    Becker, Georg; Müller, Antje; Braune, Stefan; Büttner, Thomas; Benecke, Reiner; Greulich, Wolfgang; Klein, Wolfgang; Mark, Günter; Rieke, Jürgen; Thümler, Reiner

    2002-10-01

    In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an 'advanced stage' of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection. The discovery of several genetic mutations associated with IPD raises the possibility that these, or other biomarkers, of the disease may help to identify persons at risk of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related to an increased iron load of the substantia nigra. In the early clinical phase, a number of motor and particularly non-motor signs emerge, which can be identified by the patients and physicians years before the diagnosis is made, notably olfactory dysfunction, depression, or 'soft' motor signs such as changes in handwriting, speech or reduced ambulatory arm motion. These signs of the early, prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer tests. As one single instrument will not be sensitive enough, a battery of tests has to be composed measuring independent parameters of the incipient disease. Subjects with abnormal findings in this test battery should than be submitted to nuclear medicine examinations to quantify the extent of dopaminergic injury and to reach the goal of a reliable, early diagnosis.

  11. Early vitrectomy effective for Norrie disease.

    PubMed

    Walsh, Mark K; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

    2010-04-01

    To review our experience with Norrie disease to determine if early vitrectomy abrogates the natural history of this rare disease; namely, bilateral no light perception visual acuity and phthisis bulbi. We retrospectively reviewed the medical records of all patients seen in our tertiary care pediatric retinal clinical practice from 1988 through 2008 with a potential diagnosis of Norrie disease. Inclusion required not only clinical findings consistent with Norrie disease but also genetics and/or a family history consistent with Norrie disease. Medical record review revealed 14 boys with clinically diagnosed Norrie disease and either Norrie disease gene (NDP) mutations noted on genetic testing (13 patients) and/or a clear family history consistent with Norrie disease (4 patients). All 14 boys with definite Norrie disease had vitrectomy with or without lensectomy in at least 1 eye prior to 12 months of age. Of the 14 boys with definite Norrie disease, 7 maintained at least light perception visual acuity in 1 eye and 3 had no light perception visual acuity bilaterally; visual acuity data were not available for 4 patients. Only 2 of 24 (8%) eyes became phthisical. Historically, no treatment has been offered to mitigate the dismal natural history of Norrie disease. We recommend consideration of early vitrectomy in Norrie disease.

  12. Evidence for early disease-modifying drugs in rheumatoid arthritis

    PubMed Central

    Scott, David L

    2004-01-01

    Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated. PMID:14979927

  13. Mortality sensitivity in life-stage simulation analysis: A case study of southern sea otters

    USGS Publications Warehouse

    Gerber, L.R.; Tinker, M.T.; Doak, D.F.; Estes, J.A.; Jessup, David A.

    2004-01-01

    Currently, there are no generally recognized approaches for linking detailed mortality and pathology data to population-level analyses of extinction risk. We used a combination of analytical and simulation-based analyses to examine 20 years of age- and sex-specific mortality data for southern sea otters (Enhydra lutris), and we applied results to project the efficacy of alternative conservation strategies. Population recovery of the southern sea otter has been slow (rate of population increase ?? = 1.05) compared to other recovering populations (?? = 1.17-1.20), and the population declined (?? = 0.975) between 1995 and 1999. Age-based Leslie matrices were developed to explore explanations for the slow recovery and recent decline in the southern sea other population. An elasticity analysis was performed to predict effects of proportional changes in stage-specific reproductive or survival rates on the rate of population increase. A life-stage simulation analysis (LSA) was developed to evaluate the impact of changing age- and cause-specific mortality rates on ??. The information used to develop these models was derived from death assemblage, pathology, and live population census data to examine the sensitivity of sea otter population growth to different sources of mortality (e.g., disease and starvation, direct human take [fisheries, gun shot, boat strike, oil pollution], mating trauma and intraspecific aggression, shark bites, and unknown). We used resampling simulations to generate random combinations of vital rates for a large number of matrix replicates and drew on these to estimate potential effects of mortality sources on population growth (??). Our analyses suggest management actions that are likely and unlikely to promote recovery of the southern sea otter and more broadly indicate a methodology to better utilize cause-of-death data in conservation decision-making.

  14. The Intestinal Microbiome in Early Life: Health and Disease

    PubMed Central

    Arrieta, Marie-Claire; Stiemsma, Leah T.; Amenyogbe, Nelly; Brown, Eric M.; Finlay, Brett

    2014-01-01

    Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about 3 years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their health status as well as their immune system. An ever-expanding number of articles associate several diseases with early-life imbalances of the gut microbiota, also referred to as gut microbial dysbiosis. Whether early-life dysbiosis precedes and plays a role in disease pathogenesis, or simply originates from the disease process itself is a question that is beginning to be answered in a few diseases, including IBD, obesity, and asthma. This review describes the gut microbiome structure and function during the formative first years of life, as well as the environmental factors that determine its composition. It also aims to discuss the recent advances in understanding the role of the early-life gut microbiota in the development of immune-mediated, metabolic, and neurological diseases. A greater understanding of how the early-life gut microbiota impacts our immune development could potentially lead to novel microbial-derived therapies that target disease prevention at an early age. PMID:25250028

  15. Realizing the Potential of Adolescence to Prevent Transgenerational Conditioning of Noncommunicable Disease Risk: Multi-Sectoral Design Frameworks

    PubMed Central

    Bay, Jacquie L.; Morton, Susan M.; Vickers, Mark H.

    2016-01-01

    Evidence from the field of Developmental Origins of Health and Disease (DOHaD) demonstrates that early life environmental exposures impact later-life risk of non-communicable diseases (NCDs). This has revealed the transgenerational nature of NCD risk, thus demonstrating that interventions to improve environmental exposures during early life offer important potential for primary prevention of DOHaD-related NCDs. Based on this evidence, the prospect of multi-sectoral approaches to enable primary NCD risk reduction has been highlighted in major international reports. It is agreed that pregnancy, lactation and early childhood offer significant intervention opportunities. However, the importance of interventions that establish positive behaviors impacting nutritional and non-nutritional environmental exposures in the pre-conceptual period in both males and females, thus capturing the full potential of DOHaD, must not be overlooked. Adolescence, a period where life-long health-related behaviors are established, is therefore an important life-stage for DOHaD-informed intervention. DOHaD evidence underpinning this potential is well documented. However, there is a gap in the literature with respect to combined application of theoretical evidence from science, education and public health to inform intervention design. This paper addresses this gap, presenting a review of evidence informing theoretical frameworks for adolescent DOHaD interventions that is accessible collectively to all relevant sectors. PMID:27417627

  16. Development of a Metabolic Biosignature for Detection of Early Lyme Disease

    PubMed Central

    Molins, Claudia R.; Ashton, Laura V.; Wormser, Gary P.; Hess, Ann M.; Delorey, Mark J.; Mahapatra, Sebabrata; Schriefer, Martin E.; Belisle, John T.

    2015-01-01

    Background. Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%–40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Methods. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Results. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%–95%), and a specificity of 95% (90%–100%). Importantly, the metabolic biosignature correctly classified 77%–95% of the of serology negative Lyme disease patients. Conclusions. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P < .0001) diagnostic sensitivity than current 2-tier serology, while retaining high specificity. PMID:25761869

  17. Development of a metabolic biosignature for detection of early Lyme disease.

    PubMed

    Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Hess, Ann M; Delorey, Mark J; Mahapatra, Sebabrata; Schriefer, Martin E; Belisle, John T

    2015-06-15

    Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%-40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%-95%), and a specificity of 95% (90%-100%). Importantly, the metabolic biosignature correctly classified 77%-95% of the of serology negative Lyme disease patients. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P < .0001) diagnostic sensitivity than current 2-tier serology, while retaining high specificity. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Early detection of contagious diseases

    DOEpatents

    Colston, Jr., Billy W.; Milanovich, Fred P [Lafayette, CA; Estacio, Pedro [Mission San Jose, CA; Chang, John [Walnut Creek, CA

    2011-08-09

    This invention provides an electronic proximity apparatus and a surveillance method using such an apparatus for alerting individuals that are exposed to a contagious disease. When a person becomes symptomatic and is diagnosed as positive for a given contagious agent, individuals that have recently maintained a threshold proximity with respect to an infected individual are notified and advised to seek immediate medial care. Treatment of individuals in the very early phases of infection (pre-symptomatic) significantly reduces contagiousness of the infected population first exposed to the contagious disease, thus preventing spread of the disease throughout the general population.

  19. Nanomedicine for Early Disease Detection and Treatment

    DTIC Science & Technology

    2013-09-01

    AD_________________ Award Number: W81XWH-11-1-0442 TITLE: Nanomedicine for early disease ...been developed to report and cure diseases . ESNM is prepared with multiple layers of polyelectrolytes, sequentially assembled on an inert gold...molecular characteristics of the patient and his/her specific diseased tissues with the treatment. In order to maximize therapeutic effects and

  20. Early childhood poverty, immune-mediated disease processes, and adult productivity.

    PubMed

    Ziol-Guest, Kathleen M; Duncan, Greg J; Kalil, Ariel; Boyce, W Thomas

    2012-10-16

    This study seeks to understand whether poverty very early in life is associated with early-onset adult conditions related to immune-mediated chronic diseases. It also tests the role that these immune-mediated chronic diseases may play in accounting for the associations between early poverty and adult productivity. Data (n = 1,070) come from the US Panel Study of Income Dynamics and include economic conditions in utero and throughout childhood and adolescence coupled with adult (age 30-41 y) self-reports of health and economic productivity. Results show that low income, particularly in very early childhood (between the prenatal and second year of life), is associated with increases in early-adult hypertension, arthritis, and limitations on activities of daily living. Moreover, these relationships and particularly arthritis partially account for the associations between early childhood poverty and adult productivity as measured by adult work hours and earnings. The results suggest that the associations between early childhood poverty and these adult disease states may be immune-mediated.

  1. Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases.

    PubMed

    Okazawa, Hitoshi

    2017-01-01

    The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.

  2. Chemical defense of early life stages of benthic marine invertebrates.

    PubMed

    Lindquist, Niels

    2002-10-01

    Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

  3. Glaucoma as an early complication of Hurler's disease.

    PubMed Central

    Nowaczyk, M J; Clarke, J T; Morin, J D

    1988-01-01

    We report three cases of Hurler's disease in which glaucoma developed in early childhood. We draw attention to the fact that glaucoma may be a commonly unrecognised early complication of this condition. PMID:3140740

  4. Pathologic features of early inflammatory bowel disease.

    PubMed

    Finkelstein, Sydney D; Sasatomi, Eizaburo; Regueiro, Miguel

    2002-03-01

    Often the pathologic changes of IBD are subtle and may not be present in a proportion of biopsy specimens. In cases of early disease, the changes may be missed, and additional specimens should be taken after a period of time. Modifying factors, such as prebiopsy treatment and coexisting disease, should be considered. A forum to review cases and allow for communication between gastroenterologists and pathologists is especially useful for clinicopathologic correlation and assignment of a working diagnosis to each case. Careful attention to the pathologic features of early UC and CD would be most useful when evaluating new therapies for IBD.

  5. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2015-04-01

    autosomal recessive early-onset Parkinson’s disease and juvenile Parkinson disease , Parkin has been shown to promote intracellular Abeta1–42 clearance [15... Parkinsonism . Conclusions Mutations were found in 6/50 families. The presence of an APOE-4 allele may account for disease status in one affected non...AD_________________ Award Number: W81XWH-12-1-0013 TITLE: Whole Exome Analysis of Early Onset Alzheimer’s Disease PRINCIPAL INVESTIGATOR

  6. Biomarker for early renal microvascular and diabetic kidney diseases.

    PubMed

    Futrakul, Narisa; Futrakul, Prasit

    2017-11-01

    Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

  7. Biomarkers for early detection of Alzheimer disease.

    PubMed

    Barber, Robert C

    2010-09-01

    The existence of an effective biomarker for early detection of Alzheimer disease would facilitate improved diagnosis and stimulate therapeutic trials. Multidisciplinary clinical diagnosis of Alzheimer disease is time consuming and expensive and relies on experts who are rarely available outside of specialty clinics. Thus, many patients do not receive proper diagnosis until the disease has progressed beyond stages in which treatments are maximally effective. In the clinical trial setting, rapid, cost-effective screening of patients for Alzheimer disease is of paramount importance for the development of new treatments. Neuroimaging of cortical amyloid burden and volumetric changes in the brain and assessment of protein concentrations (eg, β-amyloid 1-42, total tau, phosphorylated tau) in cerebrospinal fluid are diagnostic tools that are not widely available. Known genetic markers do not provide sufficient discriminatory power between different forms of dementia to be useful in isolation. Recent studies using panels of biomarkers for diagnosis of Alzheimer disease or mild cognitive impairment have been promising, though no such studies have been cross-validated in independent samples of subjects. The ideal biomarker enabling early detection of Alzheimer disease has not yet been identified.

  8. The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

    PubMed Central

    Goetz, Christopher G.

    2011-01-01

    Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease. PMID:22229124

  9. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    ClinicalTrials.gov

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

  10. Chronic granulomatous disease mimicking early-onset Crohn's disease with cutaneous manifestations.

    PubMed

    Barbato, Maria; Ragusa, Giovanni; Civitelli, Fortunata; Marcheggiano, Adriana; Di Nardo, Giovanni; Iacobini, Metello; Melengu, Taulant; Cucchiara, Salvatore; Duse, Marzia

    2014-06-20

    Chronic granulomatous disease is a rare inherited disorder of the innate immune system. In patients with a clinical history of recurrent or persistent infections, especially infections caused by uncommon species, chronic granulomatous disease should be considered. We report the case of a 5-year-old boy with a presumptive diagnosis of Crohn's disease with extraintestinal manifestations. Chronic granulomatous disease was suspected in this case after Serratia marcescens was isolated from a skin ulcer culture. Granulomas were confirmed on histology and chronic granulomatous disease was diagnosed. This case emphasizes the importance of high clinical suspicion of an alternative diagnosis of immune deficiency in patients with presumed inflammatory bowel disease and opportunistic infections, especially when disease occurs in early life.

  11. Office-based spirometry for early detection of obstructive lung disease.

    PubMed

    Wallace, Laura D; Troy, Kenneth E

    2006-09-01

    To review the research-based evidence supporting smoking cessation as the only proven method to reduce chronic obstructive pulmonary disease (COPD) progression and to show that early detection of disease with office-based spirometry can lead to therapeutic intervention before physiologic symptoms arise. Extensive review of national and international scientific literature supplemented with drawings and algorithms. Early detection of COPD with spirometry, along with smoking cessation, and aggressive intervention can alter the insidious course of this highly preventable disease. It is imperative that nurse practitioners utilize this simple and inexpensive procedure to identify COPD in its earliest stages, so treatment can reduce individual and community disease burden, reduce morbidity and mortality, and help reduce healthcare costs. Determination of early airflow obstruction supports smoking cessation education, provides objective data for patient motivation, thereby doubling patient compliance and reducing further disease burden.

  12. Peripheral Synucleinopathy in Early Parkinson’s Disease: Submandibular Gland Needle Biopsy Findings

    PubMed Central

    Adler, Charles H.; Dugger, Brittany N.; Hentz, Joseph G.; Hinni, Michael L.; Lott, David G.; Driver-Dunckley, Erika; Mehta, Shyamal; Serrano, Geidy; Sue, Lucia I.; Duffy, Amy; Intorcia, Anthony; Filon, Jessica; Pullen, Joel; Walker, Douglas G.; Beach, Thomas G.

    2015-01-01

    Background Finding a peripheral tissue biopsy site to diagnose early Parkinson’s disease would be of value for clinical care, biomarker validation, and as research enrollment criteria. While autopsy and advanced Parkinson’s disease studies suggest submandibular gland is an important biopsy site, there are no studies in early Parkinson’s disease. Objectives Determine whether needle biopsy of the submandibular gland reveals Lewy type α-synucleinopathy in early Parkinson’s disease. Methods Twenty-five early Parkinson’s disease (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated α-synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive. Results Mean (Standard Deviation) age 69.5 (8.3) for Parkinson’s disease group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six Parkinson’s disease and one control subject had inadequate glandular tissue. Positive staining was found in 14/19 (74%) Parkinson’s disease and 2/9 (22%) control subjects. Parkinson’s disease positive and negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient. Conclusions Submandibular gland needle biopsies identified phosphorylated α-synuclein staining in 74% of early Parkinson’s disease subjects. False positives may be true false positives or may represent prodromal Parkinson’s disease. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early Parkinson’s disease may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation. PMID:26799362

  13. Metabolic Differentiation of Early Lyme Disease from Southern Tick-Associated Rash Illness (STARI)

    PubMed Central

    Molins, C. R.; Ashton, L. V.; Wormser, G. P.; Andre, B. G.; Hess, A. M.; Delorey, M. J.; Pilgard, M. A.; Johnson, B. J.; Webb, K.; Islam, M. N.; Pegalajar-Jurado, A; Molla, I.; Jewett, M. W.; Belisle, J. T.

    2017-01-01

    Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is co-prevalent with Lyme disease in portions of the Eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N-acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. More importantly, development of classification models with the 261 MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to objectively distinguish early Lyme disease from an illness with nearly identical symptoms. PMID:28814545

  14. Early recognition of Cushing's disease: a case study.

    PubMed

    Iuliano, Sherry L; Laws, Edward R

    2013-08-01

    To present a case study of a 34-year-old woman with Cushing's disease and provide nurse practitioners (NPs) with the understanding of the clinical presentation needed for early recognition and treatment of the disease. A comprehensive review of published literature on Cushing's disease. Findings from history, physical examination, and diagnostic studies of a woman presenting to primary care NPs, physicians and other healthcare providers with multiple symptoms of Cushing's disease. Cushing's disease is the result of the pituitary gland producing excess amounts of adrenocorticotropic hormone (ACTH) causing the overproduction of cortisol. The disease is fairly rare and is seen mostly in women. Common chief complaints include increased facial hair, weight gain, amenorrhea, changes in the face, neck, and abdomen, with muscle wasting of the lower extremities. Untreated, diabetes mellitus and hypertension can occur and increase the patient's morbidity and mortality. Early recognition and appropriate referral can reverse the signs and symptoms over time and lead to a significantly improved quality of life. This case presented the challenges faced by NPs and physicians in diagnosing patients with Cushing's disease. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

  15. Early bronchopulmonary involvement in Crohn disease: a case report

    PubMed Central

    Valletta, Enrico; Bertini, Marina; Sette, Luciano; Braggion, Cesare; Pradal, Ugo; Zannoni, Marina

    2001-01-01

    Background Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. Case presentation A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. Conclusions Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD. PMID:11734067

  16. Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease.

    PubMed

    Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

    2009-07-28

    To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 +/- 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 +/- 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

  17. Urine biomarkers in the early stages of diseases: current status and perspective.

    PubMed

    Jing, Jian; Gao, Youhe

    2018-02-01

    As a noninvasive and easily available biological fluid, the urine is becoming an important source for disease biomarker study. Change is essential for the usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate more changes, especially in the early stages of diseases. In this review, we summarize current status and discuss perspectives on the discovery of urine biomarkers in the early stages of diseases. We emphasize the advantages of urine biomarkers compared to plasma biomarkers for the diagnosis of diseases at early stages, propose a urine biomarker research roadmap, and highlight a novel membrane storage technique that enables large-scale urine sample collection and storage efficiently and economically. It is anticipated that urine biomarker studies will greatly promote early diagnosis, prevention, treatment, and prognosis of a variety of diseases, and provide strong support for translational and precision medicine.

  18. ASSESSING SUSCEPTIBILITY FROM EARLY-LIFE EXPOSURE TO CARCINOGENS

    EPA Science Inventory

    Cancer risks from childhood exposures to chemicals are generally analyzed using methods based upon exposure from adults, which assumes chemicals are equally potent for inducing risks at these different lifestages. Published literature was evaluated to determine whether there was...

  19. Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).

    PubMed

    Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Andre, Barbara G; Hess, Ann M; Delorey, Mark J; Pilgard, Mark A; Johnson, Barbara J; Webb, Kristofor; Islam, M Nurul; Pegalajar-Jurado, Adoracion; Molla, Irida; Jewett, Mollie W; Belisle, John T

    2017-08-16

    Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N -acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  20. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

    PubMed

    Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

    2012-04-15

    Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

  1. Urinary Biomarkers at Early ADPKD Disease Stage

    PubMed Central

    Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

    2015-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

  2. Confidence interval estimation of the difference between two sensitivities to the early disease stage.

    PubMed

    Dong, Tuochuan; Kang, Le; Hutson, Alan; Xiong, Chengjie; Tian, Lili

    2014-03-01

    Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Limbic grey matter changes in early Parkinson's disease.

    PubMed

    Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

    2017-05-02

    The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The

  4. Early-Life Nutritional Programming of Health and Disease in The Gambia.

    PubMed

    Moore, Sophie E

    2017-01-01

    Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality. © 2017 S. Karger AG, Basel.

  5. Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

    PubMed Central

    Pohl, Calvin S.; Medland, Julia E.

    2015-01-01

    Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

  6. The design of composite monitoring scheme for multilevel information in crop early diseases

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Meng, Qinglong; Shang, Jing

    2018-02-01

    It is difficult to monitor and predict the crops early diseases in that the crop disease monitoring is usually monitored by visible light images and the availabilities in early warning are poor at present. The features of common nondestructive testing technology applied to the crop diseases were analyzed in this paper. Based on the changeable characteristics of the virus from the incubation period to the onset period of crop activities, the multilevel composite information monitoring scheme were designed by applying infrared thermal imaging, visible near infrared hyperspectral imaging, micro-imaging technology to the monitoring of multilevel information of crop disease infection comprehensively. The early warning process and key monitoring parameters of compound monitoring scheme are given by taking the temperature, color, structure and texture of crops as the key monitoring characteristics of disease. With overcoming the deficiency that the conventional monitoring scheme is only suitable for the observation of diseases with naked eyes, the monitoring and early warning of the incubation and early onset of the infection crops can be realized by the composite monitoring program as mentioned in this paper.

  7. Destructive bone disease in early syphilis.

    PubMed

    Dismukes, W E; Delgado, D G; Mallernee, S V; Myers, T C

    1976-12-06

    Although destructive bone disease is a well-known complication of tertiary syphilis, osteitis or osteomyelitis are not commonly recognized as complications of early (primary or secondary) syphillis. A patient with secondary syphilis characterized by generalized lymphadenopathy, perianal condyloma lata, and positive rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS) tests also complained of headache, right should pain, and right anterior chest pain and swelling. Roentgenograms showed mottled osteolytic lesions consistent with previously described luetic bone disease. Biopsy confirmed the diagnosis of syphilitic osteomyelitis, and treatment with penicillin resulted in prompt resolution of symptoms.

  8. Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

    PubMed

    Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

    2012-12-01

    Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Magnetic resonance imaging for diagnosis of early Alzheimer's disease.

    PubMed

    Colliot, O; Hamelin, L; Sarazin, M

    2013-10-01

    A major challenge for neuroimaging is to contribute to the early diagnosis of Alzheimer's disease (AD). In particular, magnetic resonance imaging (MRI) allows detecting different types of structural and functional abnormalities at an early stage of the disease. Anatomical MRI is the most widely used technique and provides local and global measures of atrophy. The recent diagnostic criteria of "mild cognitive impairment due to AD" include hippocampal atrophy, which is considered a marker of neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in the hippocampus and throughout the whole brain. Recent modalities such as diffusion-tensor imaging and resting-state functional MRI provide additional measures that could contribute to the early diagnosis but require further validation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

    PubMed

    Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

    2018-01-01

    To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn’s disease

    PubMed Central

    Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

    2009-01-01

    AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn’s disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients. PMID:19630105

  12. Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

    PubMed

    Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

    2015-12-15

    Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

  13. Chlorophyll as a biomarker for early disease diagnosis

    NASA Astrophysics Data System (ADS)

    Manzoor Atta, Babar; Saleem, M.; Ali, Hina; Arshad, Hafiz Muhammad Imran; Ahmed, M.

    2018-06-01

    The current study was designed to identify the stage for the diagnosis of disease before visible symptoms appeared. Fluorescence spectroscopy has been employed to identify disease signatures for its early diagnosis in rice plant leaves. Bacterial leaf blight (BLB) diseased and healthy leaf samples were collected from the rice fields in September, 2017 which were then used to record spectra using an excitation wavelength at 410 nm. The spectral range of emission was set from 420 to 800 nm which covers the blue–green and the chlorophyll bands. It was found that diseased leaves have a narrower ‘chlorophyll a’ band than healthy ones, and furthermore, that the emission band at 730 nm was either declined or depleted in the sample with high infection symptoms. In contrast, the blue–green region was observed to increase due to the emergence of disease. As the band intensity of chlorophyll decreases during infection, this decrease in chlorophyll content and increase in the blue–green spectral region could provide a new approach for predicting BLB at an early stage. The important finding was that the chlorophyll degradation and rise in the blue–green region take place in leaves with BLB or during BLB infection. Principal component analysis has been applied to spectral data which successfully separated diseased samples from healthy ones even with very small spectral variations.

  14. Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson's Disease.

    PubMed

    San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B; Lipton, Richard B; Pullman, Seth; Saunders-Pullman, Rachel

    2016-01-01

    Pre-clinical markers of Parkinson's Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD.

  15. Early rheumatoid disease. II. Patterns of joint involvement.

    PubMed Central

    Fleming, A; Benn, R T; Corbett, M; Wood, P H

    1976-01-01

    Data from the first research clinic visit (Fleming and others, 1976) have been subjected to factor analysis to identify early patterns of joint involvement. Nine patterns emerged. Two patterns, if present early, were found to have prognostic significance. An eventually more severe disease was associated with a pattern of large joint involvement (shoulder, elbow, wrist, knee) and a pattern based on metatarsophalangeal joints I and III. PMID:970995

  16. Orthostatic hypotension predicts motor decline in early Parkinson disease.

    PubMed

    Kotagal, Vikas; Lineback, Christina; Bohnen, Nicolaas I; Albin, Roger L

    2016-11-01

    Orthostatic hypotension is increasingly reported as a risk factor for development of late-stage disease features in Parkinson disease (PD). Less is known about its significance in individuals with early PD who are often targeted for neuroprotective trials. Using data from the CALM-PD trial (n = 275), we explored whether early orthostatic hypotension predicts a decline in the Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living) or UDPRS III (motor) score after 102 weeks. We also explored risk factors for worsening orthostatic hypotension over a nearly 2-year period. After controlling for age, disease duration, gender, study drug, change in mini-mental status exam score, levodopa equivalent dose, and baseline UPDRS II or III score respectively, the degree of orthostatic hypotension at enrollment associated with a worsening in UPDRS motor score (t = 2.40, p = 0.017) at week 102 but not with UPDRS ADL score (t = 0.83, p = 0.409). Worsening in orthostatic hypotension during the study associated with longer disease duration (t = 2.37, p = 0.019) and lower body mass index (BMI) (t = -2.96, p = 0.003). Baseline orthostatic hypotension is a predictor of UPDRS motor decline in individuals with early PD and should be accounted for in clinical trial design. Low BMI may predict orthostatic hypotension in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The die is cast - Arsenic exposure in early life and disease susceptibility

    EPA Science Inventory

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  18. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

    PubMed Central

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

  19. Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

    2015-01-01

    One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

  20. Computer keyboard interaction as an indicator of early Parkinson's disease.

    PubMed

    Giancardo, L; Sánchez-Ferro, A; Arroyo-Gallego, T; Butterworth, I; Mendoza, C S; Montero, P; Matarazzo, M; Obeso, J A; Gray, M L; Estépar, R San José

    2016-10-05

    Parkinson's disease (PD) is a slowly progressing neurodegenerative disease with early manifestation of motor signs. Objective measurements of motor signs are of vital importance for diagnosing, monitoring and developing disease modifying therapies, particularly for the early stages of the disease when putative neuroprotective treatments could stop neurodegeneration. Current medical practice has limited tools to routinely monitor PD motor signs with enough frequency and without undue burden for patients and the healthcare system. In this paper, we present data indicating that the routine interaction with computer keyboards can be used to detect motor signs in the early stages of PD. We explore a solution that measures the key hold times (the time required to press and release a key) during the normal use of a computer without any change in hardware and converts it to a PD motor index. This is achieved by the automatic discovery of patterns in the time series of key hold times using an ensemble regression algorithm. This new approach discriminated early PD groups from controls with an AUC = 0.81 (n = 42/43; mean age = 59.0/60.1; women = 43%/60%;PD/controls). The performance was comparable or better than two other quantitative motor performance tests used clinically: alternating finger tapping (AUC = 0.75) and single key tapping (AUC = 0.61).

  1. Early life nutritional programming of health and disease in The Gambia.

    PubMed

    Moore, S E

    2016-04-01

    Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The 'Developmental Origins of Health and Disease' (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a 'mismatch' between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the 'experiment of nature' that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs.

  2. Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

    PubMed Central

    Tain, You-Lin; Hsu, Chien-Ning

    2017-01-01

    Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

  3. Byler disease: early natural history.

    PubMed

    Morris, Amy L; Bukauskas, Kathryn; Sada, Rachel E; Shneider, Benjamin L

    2015-04-01

    Byler disease, originally described in Amish kindred, results from mutations in ATPase Class I Type 8b Member 1 (ATP8b1). Specific clinical reports of Amish Byler disease were last published 40 years ago. These investigations were directed at the present detailed clinical understanding of the early course of hepatic manifestations of Byler disease. This study analyzed routine clinical practice and outcomes of children with Byler disease (defined by homozygous c.923G>T mutation in ATP8b1), who initially presented to Children's Hospital of Pittsburgh of UPMC between January 2007 and October 2014. Data were analyzed to the earlier of 24 months of age or partial external biliary diversion. Six children presented between 1 and 135 days of life: 2 presented with newborn direct hyperbilirubinemia, 2 had complications of coagulopathy, 1 had failure to thrive and rickets, and 1 sibling was identified by newborn genetic testing. Intensive fat-soluble vitamin supplementation was required to prevent insufficiencies in vitamins D, E, and K. Hyperbilirubinemia was variable both over time and between children. Serum bile acid levels were elevated, whereas γ-glutamyltranspeptidase levels were low normal. Scratching behavior (pruritus) was intractable in 4 of 6 children with onset between 6 and 12 months of age. Features of portal hypertension were not observed. Partial external biliary diversion was used during the second year of life in 4 children. Detailed analysis of Byler disease revealed varied disease presentation and course. Nutritional issues and pruritus dominated the clinical picture in the first 2 years of life.

  4. Cavallin et al 2015

    EPA Pesticide Factsheets

    This study demonstrates the potential of whole-mount in situ hybridization (WISH), in conjunction with quantitative real-time polymerase chain reaction (QPCR) assays, to examine the mechanistic basis of the effects of toxicants on early-lifestage fathead minnows. Specifically, fathead minnow embryos were exposed to the environmentally-relevant estrogen receptor agonist, estrone, and the data show that: (1) the estrogen-responsive gene transcripts esr1, vtg, and cyp19b can be up-regulated in very early-lifestages of the fathead minnow, (2) WISH methods developed for zebrafish can also be applied successfully to fathead minnows, and (3) WISH has potential to be a useful tool for toxicological studies pertaining to early-lifestage development in the fathead minnow. This type of mechanistic information relative to spatial distribution of gene expression is important in determining potential biological pathways that may be impacted by targeted chemicals and the development of associated adverse outcome pathways.This dataset is associated with the following publication:Cavallin, J., A. Schroeder, K. Jensen , D. Villeneuve , B. Blackwell, K. Carlson, M. Kahl , C. LaLone , E. Randolph , and G. Ankley. Evaluation of whole-mount in situ hybridization as a tool for pathway-based toxicological research with early-life stage fathead minnows. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 169: 19-26, (2015).

  5. Diagnostic challenges of early Lyme disease: Lessons from a community case series

    PubMed Central

    2009-01-01

    Background Lyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown. Methods A retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments. Results The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease. Conclusion For community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations. PMID:19486523

  6. Operational Thought in Alzheimer's Disease Early Onset and SDAT.

    ERIC Educational Resources Information Center

    Emery, Olga B.; Breslau, Lawrence D.

    For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

  7. Development of the Paris definition of early Crohn's disease for disease-modification trials: results of an international expert opinion process.

    PubMed

    Peyrin-Biroulet, Laurent; Billioud, Vincent; D'Haens, Geert; Panaccione, Remo; Feagan, Brian; Panés, Julian; Danese, Silvio; Schreiber, Stefan; Ogata, Haruhiko; Hibi, Toshifumi; Higgins, Peter D R; Beaugerie, Laurent; Chowers, Yehuda; Louis, Edouard; Steinwurz, Flávio; Reinisch, Walter; Rutgeerts, Paul; Colombel, Jean-Frédéric; Travis, Simon; Sandborn, William J

    2012-12-01

    We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen experts on inflammatory bowel diseases held an international expert opinion meeting to discuss and agree on a definition for early CD to be used in disease-modification trials. The process included literature searches for the relevant basic-science and clinical evidence. A published preliminary definition of early CD was used as the basis for development of a proposed definition that was discussed at the expert opinion meeting. The participants then derived a final definition, based on best current knowledge, that it is hoped will be of practical use in disease-modification trials in CD.

  8. Association of rheumatic diseases with early exit from paid employment in Portugal.

    PubMed

    Laires, Pedro A; Gouveia, Miguel

    2014-04-01

    To examine the association between rheumatic diseases (RD) and other chronic morbidity with early exit from paid employment in the Portuguese population. The study population consisted of all people between 50 and 64 years of age (3,762 men and 4,241 women) who participated in the Portuguese National Health Survey, conducted in 2005/2006. Data were collected on demographics, ill-health, lifestyle, and socioeconomic factors. Logistic regression was used to estimate the isolated effect of rheumatic diseases and other chronic diseases on the likelihood of exit from paid employment. At the time of the survey, 45.1 % of the Portuguese population with ages between 50 and 64 years old were not employed. In the nonemployed population, 31.6 % self-reported "poor" to "very poor" health, whereas 16.4 % did so in the employed population. A larger average number of major chronic diseases per capita were also found in those not employed (1.9 vs. 1.4, p < 0.001). In the multivariate models, chronic diseases were associated with early exit from paid employment. In particular, rheumatic diseases were more prevalent (43.4 vs. 32.1 %) and associated with early exit from work (OR 1.31; CI 1.12-1.52, p = 0.001). This study suggests an association between RD and other major chronic diseases with early exit from paid employment in Portugal. Thus, health and social protection policies should target these chronic disorders in order to better address sustainability issues and social protection effectiveness.

  9. Informativeness of Early Huntington Disease Signs about Gene Status.

    PubMed

    Oster, Emily; Eberly, Shirley W; Dorsey, E Ray; Kayson-Rubin, Elise; Oakes, David; Shoulson, Ira

    2015-01-01

    The cohort-level risk of Huntington disease (HD) is related to the age and symptom level of the cohort, but this relationship has not been made precise. To predict the evolving likelihood of carrying the Huntington disease (HD) gene for at-risk adults using age and sign level. Using data from adults with early signs and symptoms of HD linked to information on genetic status, we use Bayes' theorem to calculate the probability that an undiagnosed individual of a certain age and sign level has an expanded CAG repeat. Both age and sign levels have substantial influence on the likelihood of HD onset, and the probability of eventual diagnosis changes as those at risk age and exhibit (or fail to exhibit) symptoms. For example, our data suggest that in a cohort of individuals age 26 with a Unified Huntington's Disease Rating Scale (UHDRS) motor score of 7-10 70% of them will carry the HD mutation. For individuals age 56, the same motor score suggests only a 40% chance of carrying the mutation. Early motor signs of HD, overall and the chorea subscore, were highly predictive of disease onset at any age. However, body mass index (BMI) and cognitive performance scores were not as highly predictive. These results suggest that if researchers or clinicians are looking for early clues of HD, it may be more foretelling to look at motor rather than cognitive signs. Application of similar approaches could be used with other adult-onset genetic conditions.

  10. Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer's Disease.

    PubMed

    Cheng, Bo; Liu, Mingxia; Shen, Dinggang; Li, Zuoyong; Zhang, Daoqiang

    2017-04-01

    Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer's Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multi-domain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods.

  11. Bone density and brain atrophy in early Alzheimer's disease.

    PubMed

    Loskutova, Natalia; Honea, Robyn A; Vidoni, Eric D; Brooks, William M; Burns, Jeffrey M

    2009-01-01

    Studies suggest a link between bone loss and Alzheimer's disease. To examine bone mineral density (BMD) in early Alzheimer's disease (AD) and its relationship to brain structure and cognition, we evaluated 71 patients with early stage AD (Clinical Dementia Rating (CDR) 0.5 and 1) and 69 non-demented elderly control participants (CDR 0). Measures included whole body BMD by dual energy x-ray absorptiometry (DXA) and normalized whole brain volumes computed from structural MRI scans. Cognition was assessed with a standard neuropsychological test battery. Mean BMD was lower in the early AD group (1.11 +/- 0.13) compared to the non-demented control group (1.16 +/- 0.12, p = 0.02), independent of age, gender, habitual physical activity, smoking, depression, estrogen replacement, and apolipoprotein E4 carrier status. In the early AD group, BMD was related to whole brain volume (b = 0.18, p = 0.03). BMD was also associated with cognitive performance, primarily in tests of memory (logical memory [b = 0.15, p = 0.04], delayed logical memory [b = 0.16, p = 0.02], and the selective reminding task - free recall [b = 0.18, p = 0.009]). BMD is reduced in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early AD.

  12. Computer keyboard interaction as an indicator of early Parkinson’s disease

    PubMed Central

    Giancardo, L.; Sánchez-Ferro, A.; Arroyo-Gallego, T.; Butterworth, I.; Mendoza, C. S.; Montero, P.; Matarazzo, M.; Obeso, J. A.; Gray, M. L.; Estépar, R. San José

    2016-01-01

    Parkinson’s disease (PD) is a slowly progressing neurodegenerative disease with early manifestation of motor signs. Objective measurements of motor signs are of vital importance for diagnosing, monitoring and developing disease modifying therapies, particularly for the early stages of the disease when putative neuroprotective treatments could stop neurodegeneration. Current medical practice has limited tools to routinely monitor PD motor signs with enough frequency and without undue burden for patients and the healthcare system. In this paper, we present data indicating that the routine interaction with computer keyboards can be used to detect motor signs in the early stages of PD. We explore a solution that measures the key hold times (the time required to press and release a key) during the normal use of a computer without any change in hardware and converts it to a PD motor index. This is achieved by the automatic discovery of patterns in the time series of key hold times using an ensemble regression algorithm. This new approach discriminated early PD groups from controls with an AUC = 0.81 (n = 42/43; mean age = 59.0/60.1; women = 43%/60%;PD/controls). The performance was comparable or better than two other quantitative motor performance tests used clinically: alternating finger tapping (AUC = 0.75) and single key tapping (AUC = 0.61). PMID:27703257

  13. Computer keyboard interaction as an indicator of early Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Giancardo, L.; Sánchez-Ferro, A.; Arroyo-Gallego, T.; Butterworth, I.; Mendoza, C. S.; Montero, P.; Matarazzo, M.; Obeso, J. A.; Gray, M. L.; Estépar, R. San José

    2016-10-01

    Parkinson’s disease (PD) is a slowly progressing neurodegenerative disease with early manifestation of motor signs. Objective measurements of motor signs are of vital importance for diagnosing, monitoring and developing disease modifying therapies, particularly for the early stages of the disease when putative neuroprotective treatments could stop neurodegeneration. Current medical practice has limited tools to routinely monitor PD motor signs with enough frequency and without undue burden for patients and the healthcare system. In this paper, we present data indicating that the routine interaction with computer keyboards can be used to detect motor signs in the early stages of PD. We explore a solution that measures the key hold times (the time required to press and release a key) during the normal use of a computer without any change in hardware and converts it to a PD motor index. This is achieved by the automatic discovery of patterns in the time series of key hold times using an ensemble regression algorithm. This new approach discriminated early PD groups from controls with an AUC = 0.81 (n = 42/43 mean age = 59.0/60.1 women = 43%/60%PD/controls). The performance was comparable or better than two other quantitative motor performance tests used clinically: alternating finger tapping (AUC = 0.75) and single key tapping (AUC = 0.61).

  14. Classification of Rhinoentomophthoromycosis into Atypical, Early, Intermediate, and Late Disease: A Proposal

    PubMed Central

    Blumentrath, Christian G.; Grobusch, Martin P.; Matsiégui, Pierre-Blaise; Pahlke, Friedrich; Zoleko-Manego, Rella; Nzenze-Aféne, Solange; Mabicka, Barthélemy; Sanguinetti, Maurizio; Kremsner, Peter G.; Schaumburg, Frieder

    2015-01-01

    Background Rhinoentomophthoromycosis, or rhino-facial conidiobolomycosis, is a rare, grossly disfiguring disease due to an infection with entomophthoralean fungi. We report a case of rhinoentomophthoromycosis from Gabon and suggest a staging system, which provides information on the prognosis and duration of antifungal therapy. Methods We present a case of rhinoentomophthoromycosis including the histopathology, mycology, and course of disease. For the suggested staging system, all cases on confirmed rhinoentomophthoromycosis published in the literature without language restriction were eligible. Exclusion criteria were missing data on (i) duration of disease before correct diagnosis, (ii) outcome, and (iii) confirmation of entomophthoralean fungus infection by histopathology and/or mycology. We classified cases into atypical (orbital cellulitis, severe pain, fever, dissemination), early, intermediate, and late disease based on the duration of symptoms before diagnosis. The outcome was evaluated for each stage of disease. Findings The literature search of the Medpilot database was conducted on January 13, 2014, (updated on January 18, 2015). The search yielded 8,333 results including 198 cases from 117 papers; of these, 145 met our inclusion criteria and were included in the final analysis. Median duration of treatment was 4, 3, 4, and 5 months in atypical, early, intermediate, and late disease, respectively. Cure rates were clearly associated with stage of disease and were 57%, 100%, 82%, and 43% in atypical, early, intermediate, and late disease, respectively. Conclusion We suggest a clinical staging system that underlines the benefit of early case detection and may guide the duration of antifungal treatment. The scientific value of this classification is its capacity to structure and harmonize the clinical and research approach towards rhinoentomophthoromycosis. PMID:26426120

  15. Psychometric evaluation of a new instrument to measure disease self-management of the early stage chronic kidney disease patients.

    PubMed

    Lin, Chiu-Chu; Wu, Chia-Chen; Wu, Li-Min; Chen, Hsing-Mei; Chang, Shu-Chen

    2013-04-01

    This study aims to develop a valid and reliable chronic kidney disease self-management instrument (CKD-SM) for assessing early stage chronic kidney disease patients' self-management behaviours. Enhancing early stage chronic kidney disease patients' self-management plays a key role in delaying the progression of chronic kidney disease. Healthcare provider understanding of early stage chronic kidney disease patients' self-management behaviours can help develop effective interventions. A valid and reliable instrument for measuring chronic kidney disease patients' self-management behaviours is needed. A cross-sectional descriptive study collected data for principal components analysis with oblique rotation. Mandarin- or Taiwanese-speaking adults with chronic kidney disease (n=252) from two medical centres and one regional hospital in Southern Taiwan completed the CKD-SM. Construct validity was evaluated by exploratory factor analysis. Internal consistency and test-retest reliability were estimated by Cronbach's alpha and Pearson correlation coefficients. Four factors were extracted and labelled self-integration, problem-solving, seeking social support and adherence to recommended regimen. The four factors accounted for 60.51% of the total variance. Each factor showed acceptable internal reliability with Cronbach's alpha from 0.77-0.92. The test-retest correlations for the CKD-SM was 0.72. The psychometric quality of the CKD-SM instrument was satisfactory. Research to conduct a confirmatory factor analysis to further validate this new instrument's construct validity is recommended. The CKD-SM instrument is useful for clinicians who wish to identify the problems with self-management among chronic kidney disease patients early. Self-management assessment will be helpful to develop intervention tailored to the needs of the chronic kidney disease population. © 2013 Blackwell Publishing Ltd.

  16. Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay

    2012-10-01

    Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if self-reported early menopause (menopause at an age <46 y) identifies women as at risk for future coronary heart disease or stroke. The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46 y) and future coronary heart disease and stroke was assessed in 2,509 women (ages 45-84 y; 987 white, 331 Chinese, 641 black, and 550 Hispanic) from the Multi-ethnic Study Atherosclerosis who were free of cardiovascular disease at baseline. Of 2,509 women, 693 (28%) reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank P = 0.008 and P = 0.0158). In models adjusted for age, race/ethnicity, Multi-ethnic Study Atherosclerosis site, and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (hazard ratio, 2.08; 95% CI, 1.17-3.70; and hazard ratio, 2.19; 95% CI, 1.11-4.32, respectively). Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors.

  17. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xia, Jing; Rocke, David M.; Perry, George

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  18. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    DOE PAGES

    Xia, Jing; Rocke, David M.; Perry, George; ...

    2014-01-01

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  19. Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson’s Disease

    PubMed Central

    San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A.; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B.; Lipton, Richard B.; Pullman, Seth; Saunders-Pullman, Rachel

    2016-01-01

    Introduction Pre-clinical markers of Parkinson’s Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. Methods 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. Results All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Conclusion Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD. PMID:27732597

  20. Can early host responses to mycobacterial infection predict eventual disease outcomes?

    PubMed

    de Silva, Kumudika; Begg, Douglas J; Plain, Karren M; Purdie, Auriol C; Kawaji, Satoko; Dhand, Navneet K; Whittington, Richard J

    2013-11-01

    Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Prototype early warning system for heart disease detection using Android Application.

    PubMed

    Zennifa, Fadilla; Fitrilina; Kamil, Husnil; Iramina, Keiji

    2014-01-01

    Heart Disease affects approximately 70 million people worldwide where most people do not even know the symptoms. This research examines the prototype of early warning system for heart disease by android application. It aims to facilitate users to early detect heart disease which can be used independently. To build the application in android phone, variable centered intelligence rule system (VCIRS) as decision makers and pulse sensor - Arduino as heart rate detector were applied in this study. Moreover, in Arduino, the heart rate will become an input for symptoms in Android Application. The output of this system is the conclusion statement of users diagnosed with either coronary heart disease, hypertension heart disease, rheumatic heart disease or do not get any kind of heart disease. The result of diagnosis followed by analysis of the value of usage variable rate (VUR) rule usage rate (RUR) and node usage rate (NUR) that shows the value of the rule that will increase when the symptoms frequently appear. This application was compared with the medical analysis from 35 cases of heart disease and it showed concordance between diagnosis from android application and expert diagnosis of the doctors.

  2. Children Are Not Little Adults!

    EPA Pesticide Factsheets

    They are often more likely to be at risk from environmental hazards because of unique activity patterns/behavior, physiological differences, and windows of susceptibility during early lifestages including fetal development and puberty.

  3. Malaria: An Early Indicator of Later Disease and Work Level

    PubMed Central

    Hong, Sok Chul

    2014-01-01

    This study investigates the effect of early-life exposure to malaria on disease and work level in old age over the past one and a half centuries. Using longitudinal lifetime records of Union Army veterans, I first estimate that exposure to a malarial environment in early life (c.1840) substantially increased the likelihood of having various chronic diseases and not working in old age (c.1900). Second, from data on US cohorts born between 1891 and 1960, I find that those exposed to a higher level of the anti-malaria campaign, which began in 1921, had lower levels of work disability in old age. Third, I seek the same implications for the modern period by linking WHO's country statistics on DALYs among older populations in 2004 to country-level malaria risk in pre-eradication era. In the paper, I discuss possible mechanisms and propose the significance of malaria eradication and early-life conditions from a long-term perspective. PMID:23584052

  4. Best practices in the treatment of early cystic fibrosis lung disease.

    PubMed

    Proesmans, Marijke

    2017-02-01

    For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

  5. Disease evolution in late-onset and early-onset systemic lupus erythematosus.

    PubMed

    Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

    2017-10-01

    Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

  6. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia.

    PubMed

    Mourani, Peter M; Sontag, Marci K; Younoszai, Adel; Miller, Joshua I; Kinsella, John P; Baker, Christopher D; Poindexter, Brenda B; Ingram, David A; Abman, Steven H

    2015-01-01

    Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of pulmonary vascular disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown. To prospectively evaluate the relationship of early echocardiogram signs of pulmonary vascular disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA). Prospectively enrolled preterm infants with birthweights 500-1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH. A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% of infants, and 14% were diagnosed with late PH. Early PH was a risk factor for increased BPD severity (relative risk, 1.12; 95% confidence interval, 1.03-1.23) and late PH (relative risk, 2.85; 95% confidence interval, 1.28-6.33). Infants with late PH had greater duration of oxygen therapy and increased mortality in the first year of life (P < 0.05). Early pulmonary vascular disease is associated with the development of BPD and with late PH in preterm infants. Echocardiograms at 7 days of age may be a useful tool to identify infants at high risk for BPD and PH.

  7. The die is cast: arsenic exposure in early life and disease susceptibility.

    PubMed

    Thomas, David J

    2013-12-16

    Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

  8. Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer's disease.

    PubMed

    Schöll, Michael; Ossenkoppele, Rik; Strandberg, Olof; Palmqvist, Sebastian; Jögi, Jonas; Ohlsson, Tomas; Smith, Ruben; Hansson, Oskar

    2017-09-01

    Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease. © The Author (2017). Published by Oxford

  9. Early Menopause Predicts Future Coronary Heart Disease and Stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay

    2012-01-01

    Objective Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if a self-reported early menopause (menopause at an age <46) identifies women as at risk for future coronary heart disease or stroke. Methods The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000–2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46) and future coronary heart disease and stroke was assessed in 2509 women (ages 45–84, 987 White, 331 Chinese, 641 Black, 550 Hispanic) from the Multi-Ethnic Study Atherosclerosis, who were free of cardiovascular disease at baseline. Results 693/2509 (28%) of women reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank p=<0.008 and 0.0158). In models adjusted for age, race/ethnicity, Multi-Ethnic Study Atherosclerosis site and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (HR 2.08, 95% CI 1.17, 3.70 and 2.19, 95% CI 1.11, 4.32, respectively). Conclusions Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors. PMID:22692332

  10. [Early episodic memory impairments in Alzheimer's disease].

    PubMed

    Ergis, A-M; Eusop-Roussel, E

    2008-05-01

    Patients with Alzheimer's disease (AD) show early episodic memory impairments. Such deficits reflect specific impairments affecting one or several stages of encoding, storage and retrieval processes. However, AD patients not only have great difficulty retrieving memories and information but also suffer from distortions of memory, as intrusions and false recognitions. Intrusions can be defined as the unintentional recall of inappropriate information in a laboratory-learning tasks such as word-list recall and story recall. False recognition refers to the erroneous recognition of information that was not previously presented. The first objective of this review is to present studies from the literature that allowed a better understanding of the nature of episodic memory deficits in AD, and to examine recent research on false memories. The second part of this review is aimed at presenting recent research conducted on prospective memory (PM) in Alzheimer's disease. Prospective memory situations involve forming intentions and then realizing those intentions at some appropriate time in the future. Everyday examples of prospective memory include remembering to buy bread on the way home from work, remembering to give friends a message upon next encountering them, and remembering to take medication. Patients suffering from AD show difficulties in performing prospective tasks in daily life, according to the complaints of their care givers, and these difficulties are massively present at the first stages of the disease. Nevertheless, very few studies have been dedicated to this subject, although the evaluation of PM could be helpful for the early diagnosis of AD.

  11. Surveillance and early warning systems of infectious disease in China: From 2012 to 2014.

    PubMed

    Zhang, Honglong; Wang, Liping; Lai, Shengjie; Li, Zhongjie; Sun, Qiao; Zhang, Peng

    2017-07-01

    Appropriate surveillance and early warning of infectious diseases have very useful roles in disease control and prevention. In 2004, China established the National Notifiable Infectious Disease Surveillance System and the Public Health Emergency Event Surveillance System to report disease surveillance and events on the basis of data sources from the National Notifiable Infectious Disease Surveillance System, China Infectious Disease Automated-alert and Response System in this country. This study provided a descriptive summary and a data analysis, from 2012 to 2014, of these 3 key surveillance and early warning systems of infectious disease in China with the intent to provide suggestions for system improvement and perfection. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-12-1-0138 TITLE: Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT PRINCIPAL INVESTIGATOR...NUMBER W81XWH-12-1-0138 Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...method for early detection of amyloid plaque in Alzheimer’s disease , with three Specific Aims: #1 Develop and optimize an x-ray PCCT to explore the

  13. Early, asymptomatic stage of degenerative joint disease in canine hip joints.

    PubMed

    Lust, G; Summers, B A

    1981-11-01

    The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

  14. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    PubMed

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

  15. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2016-04-01

    Early Onset Alzheimer’s Disease 5a. CONTRACT NUMBER W81XWH-12-1-0013 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Margaret A. Pericak...relationship between SORL1, AD, and Parkinsonism . 16 Appendix V: ABCA7 Frameshift Deletion Associated with Alzheimer’s Disease in African Americans...onset Alzheimer disease identified using whole-exome sequencing G. W. Beecham1, B. W. Kunkle1, B. Vardarajan2, P. L. Whitehead1, S . Rolati1, E. R

  16. Endoscopic fluorescence imaging for early assessment of anastomotic recurrence of Crohn's disease

    NASA Astrophysics Data System (ADS)

    Mordon, Serge R.; Maunoury, Vincent; Geboes, K.; Klein, Olivier; Desreumaux, P.; Debaert, A.; Colombel, Jean-Frederic

    1999-02-01

    Crohn's disease is an inflammatory bowel disease of unknown etiology. The mechanism of the initial mucosal alterations is still unclear: ulcerations overlying lymphoid follicles and/or vasculitis have been proposed as the early lesions. We have developed a new and original method combining endoscopy of fluorescence angiography for identifying the early pathological lesions, occurring in the neo-terminal ileum after right ileocolonic resection. The patient population consisted of 10 subjects enrolled in a prospective protocol of endoscopic follow-up at 3 and 12 months after surgery. Fluorescence imaging showed small spots giving a bright fluorescence distributed singly in mucosa which appeared normal in routine endoscopy. Histopathological examination demonstrated that the fluorescence of small spots originated from small, usually superficial, erosive lesions. In several cases, these erosive lesions occurred over lymphoid follicles. Endoscopic fluorescence imaging provides a suitable means of investigating the initial aspect of the Crohn's disease process in displaying some correlative findings between fluorescent aspects and early pathological mucosal alterations.

  17. First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features

    PubMed Central

    Spencer, Michael D; Knight, Richard S G; Will, Robert G

    2002-01-01

    Objective To describe the early psychiatric and neurological features of variant Creutzfeldt-Jakob disease. Design Cohort study. Setting National surveillance system for Creutzfeldt-Jakob disease in the United Kingdom. Participants The first 100 cases of variant Creutzfeldt-Jakob disease identified in the United Kingdom. Main outcome measures The timing and nature of early psychiatric and neurological symptoms in variant Creutzfeldt-Jakob disease. Results The early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptoms, but neurological symptoms precede psychiatric symptoms in 15% of cases and are present in combination with psychiatric symptoms in 22% of cases from the onset of disease. Common early psychiatric features include dysphoria, withdrawal, anxiety, insomnia, and loss of interest. No common early neurological features exist, but a significant proportion of patients do exhibit neurological symptoms within 4 months of clinical onset, including poor memory, pain, sensory symptoms, unsteadiness of gait, and dysarthria. Conclusions Although the diagnosis of variant Creutzfeldt-Jakob disease may be impossible in the early stages of the illness, particular combinations of psychiatric and neurological features may allow early diagnosis in an appreciable proportion of patients. What is already known on this topicThe early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptomatologySome patients have early neurological features that might suggest the presence of an underlying neurological disorderWhat this study addsThis study provides a comprehensive description of the evolution of psychiatric and neurological features in variant Creutzfeldt-Jakob diseaseAn appreciable proportion of patients have early neurological symptomsA high proportion of patients have a combination of psychiatric and neurological features within four months of clinical onset that suggest the diagnosis of variant Creutzfeldt-Jakob disease

  18. 78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

    ...] Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... ``Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease.'' This guidance outlines FDA...

  19. Early retirement and income loss in patients with early and advanced Parkinson's disease.

    PubMed

    Johnson, Scott; Davis, Matthew; Kaltenboeck, Anna; Birnbaum, Howard; Grubb, Elizabeth; Tarrants, Marcy; Siderowf, Andrew

    2011-11-01

    The indirect costs of Parkinson's disease (PD) may be larger than direct healthcare costs, and the largest component of indirect costs is income loss related to early retirement. No recent retrospective analysis details PD-related early retirement and income loss in the US. We used an observational, matched cohort to study wages and labour force participation over 4 years and to simulate lifetime income losses conditional on being newly diagnosed with PD (naive) or having evidence of increasing disability. Actively employed primary beneficiaries of private insurance policies aged 18-64 years with more than two PD diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 332.x) or one diagnosis and a prescription of an antiparkinsonian drug were selected from a privately insured claims database. Continuous health coverage during analysis periods was required. Naive patients were defined as having no claims history indicative of PD during the year prior to first diagnosis or prescription use. A PD with ambulatory assistance devices (PDAAD) cohort was also followed from the date of first evidence of a wheelchair or walker. Controls without PD were matched on age, sex and region. Survival analysis and Wilcoxon rank sum tests were used to compare rates of early retirement and income loss. A simulation of projected economic loss was conducted for PD cohorts diagnosed at different ages using Bureau of Labor Statistics labour force participation and income data. Naive PD patients (n = 278) and PDAAD patients (n = 28) were on average aged 53 years and had significantly higher rates of co-morbidities at baseline versus controls. Conditional on being employed, there was no statistical difference in earnings. However, the hazard of early retirement associated with PD was 2.08 (p < 0.001) for the naive cohort and 5.01 (p < 0.001) for the PDAAD cohort. From age 40 to 79 years, earnings losses in year 2009 values were

  20. Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer’s Disease

    PubMed Central

    Cheng, Bo; Liu, Mingxia; Li, Zuoyong

    2017-01-01

    Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer’s Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multidomain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods. PMID:27928657

  1. Linguistic ability in early life and the neuropathology of Alzheimer's disease and cerebrovascular disease. Findings from the Nun Study.

    PubMed

    Snowdon, D A; Greiner, L H; Markesbery, W R

    2000-04-01

    Findings from the Nun Study indicate that low linguistic ability in early life has a strong association with dementia and premature death in late life. In the present study, we investigated the relationship of linguistic ability in early life to the neuropathology of Alzheimer's disease and cerebrovascular disease. The analyses were done on a subset of 74 participants in the Nun Study for whom we had handwritten autobiographies completed some time between the ages of 19 and 37 (mean = 23 years). An average of 62 years after writing the autobiographies, when the participants were 78 to 97 years old, they died and their brains were removed for our neuropathologic studies. Linguistic ability in early life was measured by the idea (proposition) density of the autobiographies, i.e., a standard measure of the content of ideas in text samples. Idea density scores from early life had strong inverse correlations with the severity of Alzheimer's disease pathology in the neocortex: Correlations between idea density scores and neurofibrillary tangle counts were -0.59 for the frontal lobe, -0.48 for the temporal lobe, and -0.49 for the parietal lobe (all p values < 0.0001). Idea density scores were unrelated to the severity of atherosclerosis of the major arteries at the base of the brain and to the presence of lacunar and large brain infarcts. Low linguistic ability in early life may reflect suboptimal neurological and cognitive development, which might increase susceptibility to the development of Alzheimer's disease pathology in late life.

  2. Prototype early warning systems for vector-borne diseases in Europe.

    PubMed

    Semenza, Jan C

    2015-06-02

    Globalization and environmental change, social and demographic determinants and health system capacity are significant drivers of infectious diseases which can also act as epidemic precursors. Thus, monitoring changes in these drivers can help anticipate, or even forecast, an upsurge of infectious diseases. The European Environment and Epidemiology (E3) Network has been built for this purpose and applied to three early warning case studies: (1) The environmental suitability of malaria transmission in Greece was mapped in order to target epidemiological and entomological surveillance and vector control activities. Malaria transmission in these areas was interrupted in 2013 through such integrated preparedness and response activities. (2) Since 2010, recurrent West Nile fever outbreaks have ensued in South/eastern Europe. Temperature deviations from a thirty year average proved to be associated with the 2010 outbreak. Drivers of subsequent outbreaks were computed through multivariate logistic regression models and included monthly temperature anomalies for July and a normalized water index. (3) Dengue is a tropical disease but sustained transmission has recently emerged in Madeira. Autochthonous transmission has also occurred repeatedly in France and in Croatia mainly due to travel importation. The risk of dengue importation into Europe in 2010 was computed with the volume of international travelers from dengue affected areas worldwide.These prototype early warning systems indicate that monitoring drivers of infectious diseases can help predict vector-borne disease threats.

  3. Prototype Early Warning Systems for Vector-Borne Diseases in Europe

    PubMed Central

    Semenza, Jan C.

    2015-01-01

    Globalization and environmental change, social and demographic determinants and health system capacity are significant drivers of infectious diseases which can also act as epidemic precursors. Thus, monitoring changes in these drivers can help anticipate, or even forecast, an upsurge of infectious diseases. The European Environment and Epidemiology (E3) Network has been built for this purpose and applied to three early warning case studies: (1) The environmental suitability of malaria transmission in Greece was mapped in order to target epidemiological and entomological surveillance and vector control activities. Malaria transmission in these areas was interrupted in 2013 through such integrated preparedness and response activities. (2) Since 2010, recurrent West Nile fever outbreaks have ensued in South/eastern Europe. Temperature deviations from a thirty year average proved to be associated with the 2010 outbreak. Drivers of subsequent outbreaks were computed through multivariate logistic regression models and included monthly temperature anomalies for July and a normalized water index. (3) Dengue is a tropical disease but sustained transmission has recently emerged in Madeira. Autochthonous transmission has also occurred repeatedly in France and in Croatia mainly due to travel importation. The risk of dengue importation into Europe in 2010 was computed with the volume of international travelers from dengue affected areas worldwide.These prototype early warning systems indicate that monitoring drivers of infectious diseases can help predict vector-borne disease threats. PMID:26042370

  4. Genetic architecture of evolved tolerance to PCBs in the estuarine fish Fundulus heteroclitus

    EPA Science Inventory

    Populations of Atlantic killifish (F. heteroclitus) resident to coastal estuarine habitats contaminated with halogenated aromatic hydrocarbons (HAHs) exhibit heritable resistance to the early life-stage toxicity associated with these compounds. Beyond our knowledge of the aryl hy...

  5. Loss of corticospinal tract integrity in early MS disease stages

    PubMed Central

    Neumann, Jens; Kaufmann, Jörn; Heidel, Jan; Stadler, Erhard; Sweeney-Reed, Catherine; Sailer, Michael; Schreiber, Stefanie

    2017-01-01

    Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages. Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study. Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified. Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy. PMID:28959706

  6. Early changes in cytokine expression in peste des petits ruminants disease.

    PubMed

    Baron, Jana; Bin-Tarif, Abdelghani; Herbert, Rebecca; Frost, Lorraine; Taylor, Geraldine; Baron, Michael D

    2014-02-22

    Peste des petits ruminants is a viral disease of sheep and goats that has spread through most of Africa as well as the Middle East and the Indian subcontinent. Although, the spread of the disease and its economic impact has made it a focus of international concern, relatively little is known about the nature of the disease itself. We have studied the early stages of pathogenesis in goats infected with six different isolates of Peste des petits ruminants virus representing all four known lineages of the virus. No lineage-specific difference in the pathogenicity of the virus isolates was observed, although there was evidence that even small numbers of cell culture passages could affect the degree of pathogenicity of an isolate. A consistent reduction in CD4+ T cells was observed at 4 days post infection (dpi). Measurement of the expression of various cytokines showed elements of a classic inflammatory response but also a relatively early induction of interleukin 10, which may be contributing to the observed disease.

  7. Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

    PubMed Central

    Panas, Michael W.; Mao, Rong; Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.; Rebman, Alison W.; Montoya, Jose G.; Soloski, Mark J.; Steere, Allen C.; Dattwyler, Raymond J.; Arnaboldi, Paul M.; Aucott, John N.

    2015-01-01

    The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. PMID:26447113

  8. The role of monogenic disease in children with very early onset inflammatory bowel disease.

    PubMed

    Kelsen, Judith R; Baldassano, Robert N

    2017-10-01

    Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. Patients diagnosed with IBD occurring before the age of 5 are a unique population, known as very early onset (VEO)-IBD and can be phenotypically and genetically distinct from older-onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to genomic drivers of disease that may impact our therapeutic decisions. VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression and poor response to most conventional therapies. This article will review the advances in sequencing technology that have led to identification of novel gene variants associated with disease and potentially new targeted therapeutic options. Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. Identification of the causal gene or pathways, these children may allow for true precision medicine with targeted therapy and improved disease course.

  9. Early-life sexual segregation: ontogeny of isotopic niche differentiation in the Antarctic fur seal

    NASA Astrophysics Data System (ADS)

    Kernaléguen, L.; Arnould, J. P. Y.; Guinet, C.; Cazelles, B.; Richard, P.; Cherel, Y.

    2016-09-01

    Investigating the ontogeny of niche differentiation enables to determine at which life-stages sexual segregation arises, providing insights into the main factors driving resource partitioning. We investigated the ontogeny of foraging ecology in Antarctic fur seals (Arctocephalus gazella), a highly dimorphic species with contrasting breeding strategies between sexes. Sequential δ13C and δ15N values of whiskers provided a longitudinal proxy of the foraging niche throughout the whole life of seals, from weaning, when size dimorphism is minimal to the age of 5. Females exhibited an early-life ontogenetic shift, from a total segregation during their first year at-sea, to a similar isotopic niche as breeding females as early as age 2. In contrast, males showed a progressive change in isotopic niche throughout their development such that 5-year-old males did not share the same niche as territorial bulls. Interestingly, males and females segregated straight after weaning with males appearing to feed in more southerly habitats than females. This spatial segregation was of similar amplitude as observed in breeding adults and was maintained throughout development. Such early-life niche differentiation is an unusual pattern and indicates size dimorphism and breeding constraints do not directly drive sexual segregation contrary to what has been assumed in otariid seals.

  10. The airway microbiota in early cystic fibrosis lung disease.

    PubMed

    Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

    2017-11-01

    Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

  11. DIRECT AND PHOTOACTIVATED TOXICITY OF A COMPLEX PETROLEUM MIXTURE: A COMPARISON OF SOLUBILIZATION METHODS

    EPA Science Inventory

    This work addresses several issues associated with the toxicity of a complex petroleum mixture (combined kerosene/diesel and crude oil), including developmental effects and early lifestage mortality, method of solubilization, and potential photo-activated and photo-modified toxic...

  12. Early diagnosis of mild cognitive impairment and Alzheimer's disease based on salivary lactoferrin.

    PubMed

    Carro, Eva; Bartolomé, Fernando; Bermejo-Pareja, Félix; Villarejo-Galende, Alberto; Molina, José Antonio; Ortiz, Pablo; Calero, Miguel; Rabano, Alberto; Cantero, José Luis; Orive, Gorka

    2017-01-01

    The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid β (Aβ) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity. Here, we show a novel, straight-forward, and noninvasive approach for assessment of early stages of cognitive decline. Salivary samples from cases of amnestic mild cognitive impairment (aMCI) and AD, and neurology controls were analyzed. We have discovered and validated a new single saliva biomarker, lactoferrin, which in our cross-sectional investigation perfectly discriminates clinically diagnosed aMCI and AD patients from a cognitively healthy control group. The accuracy for AD diagnosis shown by salivary lactoferrin was greater than that obtained from core cerebrospinal fluid (CSF) biomarkers, including total tau and CSF Aβ 42 . Furthermore, salivary lactoferrin can be used for population screening and for identifying those underdiagnosed subjects with very early stages of mild cognitive impairment and AD. This biomarker may offer new insights in the early diagnostics for AD.

  13. Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease

    PubMed Central

    Unschuld, Paul G.; Edden, Richard A. E.; Carass, Aaron; Liu, Xinyang; Shanahan, Megan; Wang, Xin; Oishi, Kenichi; Brandt, Jason; Bassett, Susan S.; Redgrave, Graham W.; Margolis, Russell L.; van Zijl, Peter C. M.; Barker, Peter B.; Ross, Christopher A.

    2012-01-01

    Background Huntington’s Disease (HD) is a neurodegenerative disorder characterized by early cognitive decline, which progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aims to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high field strength magnetic-resonance-spectroscopy at 7-Tesla. Methods Twelve individuals with the HD-mutation in premanifest or early stage of disease versus twelve healthy controls underwent 1H magnetic-resonance-spectroscopy (7.2ml voxel in the posterior cingulate cortex) at 7-Tesla, and also T1-weighted structural magnetic-resonance-imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning. Results Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (−9.6%, p=0.02) and glutamate levels (−10.1%, p=0.02) than controls. By contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r2=0.50, p=0.01) and glutamate (r2=0.64, p=0.002) in HD subjects. Conclusions Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in early stages of HD. N-acetylaspartate and glutamate magnetic-resonance-spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural

  14. Common variants at five new loci associated with early-onset inflammatory bowel disease.

    PubMed

    Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

    2009-12-01

    The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

  15. Accumulation of murine amyloid-β mimics early Alzheimer's disease.

    PubMed

    Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

    2015-08-01

    Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for <1% of all patients with Alzheimer's disease. The inherited form is even regarded a 'rare' disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer's disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows

  16. Assessing Contaminant Sensitivity of Endangered and Threatened Aquatic Species: Part I. Acute Toxicity of Five Chemicals

    EPA Science Inventory

    Early life-stage toxicity tests with copper and pentachlorophenol (PCP) were conducted with two species listed under the U.S. Endangered Species Act (fountain darter, Etheostoma fonticola, and spotfin chub, Cyprinella monacha) and two surrogate species (fathead minnow, Pimephales...

  17. Early Huntington's Disease Affects Movements in Transformed Sensorimotor Mappings

    ERIC Educational Resources Information Center

    Boulet, C.; Lemay, M.; Bedard, M.A.; Chouinard, M.J.; Chouinard, S.; Richer, F.

    2005-01-01

    This study examined the effect of transformed visual feedback on movement control in Huntington's disease (HD). Patients in the early stages of HD and controls performed aiming movements towards peripheral targets on a digitizing tablet and emphasizing precision. In a baseline condition, HD patients were slower but showed few precision problems in…

  18. Pathways of Prion Spread during Early Chronic Wasting Disease in Deer.

    PubMed

    Hoover, Clare E; Davenport, Kristen A; Henderson, Davin M; Denkers, Nathaniel D; Mathiason, Candace K; Soto, Claudio; Zabel, Mark D; Hoover, Edward A

    2017-05-15

    Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrP CWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrP CWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrP CWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrP CWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrP CWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrP CWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion

  19. Pathways of Prion Spread during Early Chronic Wasting Disease in Deer

    PubMed Central

    Hoover, Clare E.; Davenport, Kristen A.; Henderson, Davin M.; Denkers, Nathaniel D.; Mathiason, Candace K.; Soto, Claudio; Zabel, Mark D.

    2017-01-01

    ABSTRACT Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion

  20. Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report.

    PubMed

    Tumminello, Richard; Glaspey, Lindsey; Bhamidipati, Anita; Sheehan, Patrick; Patel, Sundip

    2017-12-01

    Disseminated Lyme disease can be difficult to diagnose, as it begins with nonspecific signs and symptoms, which, if not treated correctly, can lead to atrioventricular conduction blocks and meningitis. In addition, the diagnosis can be further complicated by potentially false-positive test results. We report a case of early-disseminated Lyme disease presenting with Borrelia meningitis and concomitant Lyme carditis, which was misdiagnosed as mononucleosis. A young, previously healthy patient had been hiking in the woods of upstate New York and 4 weeks later developed fever, night sweats, and myalgias. He was diagnosed with mononucleosis via a positive rapid heterophile agglutination antibody test to the Epstein-Barr virus at a walk-in clinic and was started on medications, but then subsequently developed left hip pain, a facial droop, and a very long first-degree atrioventricular conduction block. He went to the Emergency Department, where he had testing that confirmed disseminated Lyme disease. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the difficulty in early diagnosis of disseminated Lyme disease and how a potentially false-positive laboratory test can lead to the complications of Borrelia meningitis and Lyme carditis in untreated young healthy patients. Emergency physicians need to consider Lyme disease in patients with nonspecific signs and symptoms, especially if they have been outdoors for prolonged periods of time in Lyme-endemic areas. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. [Evaluation and analysis of monitoring and early warning functions of the occupational disease reporting system in China].

    PubMed

    Zhu, Xiaojun; Li, Tao; Liu, Mengxuan

    2015-06-01

    To evaluate the monitoring and early warning functions of the occupational disease reporting system right now in China, and to analyze their influencing factors. An improved audit tool (ODIT) was used to score the monitoring and early warning functions with a total score of 10. The nine indices were completeness of information on the reporting form, coverage of the reporting system, accessibility of criteria or guidelines for diagnosis, education and training for physicians, completeness of the reporting system, statistical methods, investigation of special cases, release of monitoring information, and release of early warning information. According to the evaluation, the occupational disease reporting system in China had a score of 5.5 in monitoring existing occupational diseases with a low score for release of monitoring information; the reporting system had a score of 6.5 in early warning of newly occurring occupational diseases with low scores for education and training for physicians as well as completeness of the reporting system. The occupational disease reporting system in China still does not have full function in monitoring and early warning. It is the education and participation of physicians from general hospitals in the diagnosis and treatment of occupational diseases and suspected occupational diseases that need to be enhanced. In addition, the problem of monitoring the incidence of occupational diseases needs to be solved as soon as possible.

  2. Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease.

    PubMed

    Rehkopf, David H; Eisen, Ellen A; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F; Slade, Martin D; Cullen, Mark R

    2015-08-01

    We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

  3. Body weight and dysautonomia in early Parkinson's disease.

    PubMed

    Umehara, T; Nakahara, A; Matsuno, H; Toyoda, C; Oka, H

    2017-05-01

    Patients with Parkinson's disease (PD) begin to lose weight several years before diagnosis, which suggests weight variation is associated with some factor(s) that precede the onset of motor symptoms. This study aimed to investigate the association of autonomic nervous system with body weight in patients with PD. The subjects were 90 patients with early de novo PD. We examined the associations of body mass index (BMI) with sympathetic nervous activity reflected in orthostatic intolerance or cardiac uptake of 123 I-metaiodobenzylguanidine and parasympathetic nervous activity reflected in constipation or heart rate variability (HRV). Twelve patients (13.3%) were overweight (BMI>25 kg/m 2 ), 62 patients (68.9%) were normal-weight (18.5≦BMI<25 kg/m 2 ), and 16 patients (17.8%) were underweight (BMI<18.5 kg/m 2 ). Underweight patients had greater disease severity and decrease in blood pressure on head-up tilt-table testing, higher cardiac washout ratio of 123 I-metaiodobenzylguanidine, and lower HRV and complained of constipation more often than those with normal-weight or overweight patients. On multiple regression analyses, the correlation of these variables with BMI maintained statistical significance after adjustment for age, sex, symptom duration, and motor subtype. Dysautonomia and disease severity are closely related to body weight independently of age, sex, symptom duration, and motor subtype. Dysautonomia may play a partial role on weight variation in the early stage of PD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. GUIDANCE ON SELECTING AGE GROUPS FOR MONITORING AND ASSESSING CHILDHOOD EXPOSURES TO ENVIRONMENTAL CONTAMINANTS

    EPA Science Inventory

    This guidance document provides a set of early-lifestage age groups for Environmental Protection Agency scientists to consider when assessing children’s exposure to environmental contaminants and the resultant potential dose. These recommended age groups are based on current und...

  5. Dental Hygienist-Led Chronic Disease Management System to Control Early Childhood Caries.

    PubMed

    Ng, Man Wai; Fida, Zameera

    2016-06-01

    Management of the complex chronic disease of early childhood caries requires a system of coordinated health care interventions which can be led by a dental hygienist and where patient self-care efforts are paramount. Even after receiving costly surgical treatment under general anesthesia in the operating room, many children develop new and recurrent caries after only 6-12 months, a sequela that can be prevented. This article describes the chronic disease management (CDM) of dental caries, a science-based approach that can prevent and control caries. In this article, we (1) introduce the concept of CDM of dental caries, (2) provide evidence that CDM improves oral health outcomes, and (3) propose a dental hygienist-led team-based oral health care approach to CDM. Although we will be describing the CDM approach for early childhood caries, CDM of caries is applicable in children, adolescents, and adults. Early childhood caries disease control requires meaningful engagement of patients and parents by the oral health care team to assist them with making behavioral changes in the unique context of their families and communities. The traditional dentist/hygienist/assistant model needs to evolve to a collaborative partnership between care providers and patients/families. This partnership will be focused on systematic risk assessment and behaviorally based management of the disease itself, with sensitivity toward the familial environment. Early pilot study results demonstrate reductions in the rates of new caries, dental pain, and referral to the operating room compared with baseline rates. Dental hygienists are the appropriate team members to lead this approach because of their expertise in behavior change and prevention. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Opportunity cost for early treatment of Chagas disease in Mexico.

    PubMed

    Ramsey, Janine M; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

    2014-04-01

    Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life.

  7. Opportunity Cost for Early Treatment of Chagas Disease in Mexico

    PubMed Central

    Ramsey, Janine M.; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

    2014-01-01

    Background Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. Methodology/Principal Findings A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. Conclusions/Significance In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life. PMID:24743112

  8. Changes in spontaneous brain activity in early Parkinson's disease.

    PubMed

    Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

    2013-08-09

    Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0

  9. Is early limited surgery associated with a more benign disease course in Crohn’s disease?

    PubMed Central

    Golovics, Petra Anna; Lakatos, Laszlo; Nagy, Attila; Pandur, Tunde; Szita, Istvan; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Lovasz, Barbara Dorottya; Mandel, Michael; Veres, Gabor; Kiss, Lajos S; Vegh, Zsuzsanna; Lakatos, Peter Laszlo

    2013-01-01

    AIM: To analyze the difference in disease course and need for surgery in patients with Crohn’s disease (CD). METHODS: Data of 506 patients with incident CD were analyzed (age at diagnosis: 31.5 ± 13.8 years). Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which includes incident CD patients diagnosed between January 1, 1977 and December 31, 2008. Follow-up data were collected until December 31, 2009. All patients included had at least 1 year of follow-up available. Patients with indeterminate colitis at diagnosis were excluded from the analysis. RESULTS: Overall, 73 patients (14.4%) required resective surgery within 1 year of diagnosis. Steroid exposure and need for biological therapy were lower in patients with early limited surgery (P < 0.001 and P = 0.09). In addition, surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores (P < 0.001, HR = 0.23). The need for reoperation was also lower in patients with early limited resective surgery (P = 0.038, HR = 0.42) in a Kaplan-Meier and multivariate Cox regression (P = 0.04) analysis. However, this advantage was not observed after matching on propensity scores (PLogrank = 0.656, PBreslow = 0.498). CONCLUSION: Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery, but reoperation rates did not differ. PMID:24282358

  10. Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

    PubMed Central

    Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

    2013-01-01

    Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

  11. Early Environmental Origins of Neurodegenerative Disease in Later Life

    PubMed Central

    Landrigan, Philip J.; Sonawane, Babasaheb; Butler, Robert N.; Trasande, Leonardo; Callan, Richard; Droller, Daniel

    2005-01-01

    Parkinson disease (PD) and Alzheimer disease (AD), the two most common neurodegenerative disorders in American adults, are of purely genetic origin in a minority of cases and appear in most instances to arise through interactions among genetic and environmental factors. In this article we hypothesize that environmental exposures in early life may be of particular etiologic importance and review evidence for the early environmental origins of neurodegeneration. For PD the first recognized environmental cause, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), was identified in epidemiologic studies of drug abusers. Chemicals experimentally linked to PD include the insecticide rotenone and the herbicides paraquat and maneb; interaction has been observed between paraquat and maneb. In epidemiologic studies, manganese has been linked to parkinsonism. In dementia, lead is associated with increased risk in chronically exposed workers. Exposures of children in early life to lead, polychlorinated biphenyls, and methylmercury have been followed by persistent decrements in intelligence that may presage dementia. To discover new environmental causes of AD and PD, and to characterize relevant gene–environment interactions, we recommend that a large, prospective genetic and epidemiologic study be undertaken that will follow thousands of children from conception (or before) to old age. Additional approaches to etiologic discovery include establishing incidence registries for AD and PD, conducting targeted investigations in high-risk populations, and improving testing of the potential neurologic toxicity of chemicals. PMID:16140633

  12. Measuring Disease Progression in Early Parkinson Disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience

    PubMed Central

    Parashos, Sotirios A.; Luo, Sheng; Biglan, Kevin M.; -Wollner, Ivan Bodis; He, Bo; Liang, Grace S.; Ross, G. Webster; Tilley, Barbara C.; Shulman, Lisa M.

    2014-01-01

    Importance Optimizing assessments of rate of progression in Parkinson Disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. Objective To examine the value of measures of impairment, disability, and quality of life in assessing progression in early Parkinson disease. Design, Setting, and Participants Inception cohort analysis of data from 413 early, untreated PD patients, who were enrolled in two multicenter, randomized, double-blind clinical trials. Intervention Participants were randomized into five treatments: 67 received creatine, 66 minocycline, 71 Coenzyme Q10, 71 GPI-1485, and 138 placebo. We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Main Outcome Measure Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. Results After adjusting for baseline confounding variables Unified Parkinson Disease Rating Scale (UPDRS) II, UPDRS III, modified Rankin score (mRS), level of education, and treatment group, the rate of change of the following measurements was assessed: UPDRS II, UPDRS III, Schwab and England ADL (S&E), Total Functional Capacity (TFC), Parkinson’s Disease Quality of Life Questionnaire – 39 (PDQ39) ADL and Summary Index (SI), Short Form -12v2 Health Survey (SF12) Physical Summary (PS), and SF12 Mental Summary (MS). Variables reaching statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid worsening of UPDRS II (HR 1.15, 95% C.I. 1.08 – 1.22 for 1 scale unit change per 6 months), UPDRS III (HR 1.09; 95% C.I. 1.06 – 1.13 for 1 scale unit change per 6 months), and S&E (HR 1.29 95% C.I. 1.12 – 1.48 for 5 percentage point change per 6 months), was

  13. Varenicline improves motor and cognitive symptoms in early Huntington’s disease

    PubMed Central

    McGregor, Ailsa L; Dysart, Jo; Tingle, Malcolm D; Russell, Bruce R; Kydd, Rob R; Finucane, Gregory

    2016-01-01

    The aim of this study was to describe the effects of varenicline, a smoking cessation aid that acts as a nicotinic agonist, on cognitive function in patients with early clinical Huntington’s disease (HD) who were current smokers. Three gene-positive patients transitioning to symptomatic HD were evaluated using the Unified Huntington’s Disease Rating Scale part I and III (motor and behavioral subscales) at baseline and after 4 weeks of treatment. Cognitive function was assessed using a touch screen computer-based neurocognitive test battery (IntegNeuro®). Varenicline (1 mg twice daily) significantly improved performance in executive function and emotional recognition tasks. Our case reports describe no clinically significant adverse effects and suggest that varenicline improves aspects of cognitive function in patients with early HD. A randomized controlled study is now underway. PMID:27695336

  14. Early detection of Alzheimer disease: methods, markers, and misgivings.

    PubMed

    Green, R C; Clarke, V C; Thompson, N J; Woodard, J L; Letz, R

    1997-01-01

    There is at present no reliable predictive test for most forms of Alzheimer disease (AD). Although some information about future risk for disease is available in theory through ApoE genotyping, it is of limited accuracy and utility. Once neuroprotective treatments are available for AD, reliable early detection will become a key component of the treatment strategy. We recently conducted a pilot survey eliciting attitudes and beliefs toward an unspecified and hypothetical predictive test for AD. The survey was completed by a convenience sample of 176 individuals, aged 22-77, which was 75% female, 30% African-American, and of which 33% had a family member with AD. The survey revealed that 69% of this sample would elect to obtain predictive testing for AD if the test were 100% accurate. Individuals were more likely to desire predictive testing if they had an a priori belief that they would develop AD (p = 0.0001), had a lower educational level (p = 0.003), were worried that they would develop AD (p = 0.02), had a self-defined history of depression (p = 0.04), and had a family member with AD (p = 0.04). However, the desire for predictive testing was not significantly associated with age, gender, ethnicity, or income. The desire to obtain predictive testing for AD decreased as the assumed accuracy of the hypothetical test decreased. A better short-term strategy for early detection of AD may be computer-based neuropsychological screening of at-risk (older aged) individuals to identify very early cognitive impairment. Individuals identified in this manner could be referred for diagnostic evaluation and early cases of AD could be identified and treated. A new self-administered, touch-screen, computer-based, neuropsychological screening instrument called Neurobehavioral Evaluation System-3 is described, which may facilitate this type of screening.

  15. A 3R compliant testing strategy to predict chronic fish toxicity

    EPA Science Inventory

    To ensure an ecologically relevant basis for environmental quality standards, whole-organism vertebrate tests are considered most suitable. Currently, the fish early life-stage (FELS) test (OECD 210), which involves an exposure up to one - two months, is used to estimate chronic ...

  16. TOXICITY OF PENTACHLOROPHENOL TO ENDANGERED AND SURROGATE FISH SPECIES

    EPA Science Inventory

    Water quality criteria (WQC) generally are based on the responses of easily cultured and tested surrogate species. Little is known about the relative sensitivity of surrogate and endangered species. The objective of this study was to compare acute and chronic (early life-stage) ...

  17. Early events of citrus greening (Huanglongbing) disease development at the ultrastructural level.

    PubMed

    Folimonova, Svetlana Y; Achor, Diann S

    2010-09-01

    Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus Liberibacter asiaticus'. Understanding of the early events in HLB infection is critical for the development of effective measures to control the disease. In this work, we conducted cytopathological studies by following the development of the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing material under greenhouse conditions to examine the correlation between ultrastructural changes and symptom production, with the main objective of characterizing the early events of infection. Based on our observations, one of the first degenerative changes induced upon invasion of the pathogen appears to be swelling of middle lamella between cell walls surrounding sieve elements. This anatomical aberration was often observed in samples from newly growing flushes in inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage of HLB infection. Development of symptoms and their progression correlated with an increasing degree of microscopic aberrations. Remarkably, the ability to observe the bacterium in the infected tissue also correlated with the degree of the disease progression. Large numbers of bacterial cells were found in phloem sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we did not observe the bacteria in highly symptomatic leaf samples, suggesting a possibility that, at more advanced stages of the disease, a major proportion of 'Ca. L. asiaticus' is present in a nonviable state. We trust that observations reported here advance our understanding of how 'Ca. L. asiaticus' causes disease. Furthermore, they may be an important aid in answering a question: when and where within an infected tree the tissue serves as a better inoculum source for acquisition and transmission of the bacterium by its psyllid vector.

  18. Hyperspectral remote sensing for advanced detection of early blight (Alternaria solani) disease in potato (Solanum tuberosum) plants

    NASA Astrophysics Data System (ADS)

    Atherton, Daniel

    Early detection of disease and insect infestation within crops and precise application of pesticides can help reduce potential production losses, reduce environmental risk, and reduce the cost of farming. The goal of this study was the advanced detection of early blight (Alternaria solani) in potato (Solanum tuberosum) plants using hyperspectral remote sensing data captured with a handheld spectroradiometer. Hyperspectral reflectance spectra were captured 10 times over five weeks from plants grown to the vegetative and tuber bulking growth stages. The spectra were analyzed using principal component analysis (PCA), spectral change (ratio) analysis, partial least squares (PLS), cluster analysis, and vegetative indices. PCA successfully distinguished more heavily diseased plants from healthy and minimally diseased plants using two principal components. Spectral change (ratio) analysis provided wavelengths (490-510, 640, 665-670, 690, 740-750, and 935 nm) most sensitive to early blight infection followed by ANOVA results indicating a highly significant difference (p < 0.0001) between disease rating group means. In the majority of the experiments, comparisons of diseased plants with healthy plants using Fisher's LSD revealed more heavily diseased plants were significantly different from healthy plants. PLS analysis demonstrated the feasibility of detecting early blight infected plants, finding four optimal factors for raw spectra with the predictor variation explained ranging from 93.4% to 94.6% and the response variation explained ranging from 42.7% to 64.7%. Cluster analysis successfully distinguished healthy plants from all diseased plants except for the most mildly diseased plants, showing clustering analysis was an effective method for detection of early blight. Analysis of the reflectance spectra using the simple ratio (SR) and the normalized difference vegetative index (NDVI) was effective at differentiating all diseased plants from healthy plants, except for the

  19. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.

    PubMed

    2004-04-01

    Treatment with rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, improves symptoms of early Parkinson disease (PD). Preclinical studies suggest that this compound may also modify the progression of PD. To compare the effects of early and later initiation of rasagiline on progression of disability in patients with PD. Double-blind, parallel-group, randomized, delayed-start clinical trial. Four hundred four subjects with early PD, not requiring dopaminergic therapy, enrolled at 32 sites in the United States and Canada. Subjects were randomized to receive rasagiline, 1 or 2 mg/d, for 1 year or placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months. Change in total Unified Parkinson's Disease Rating Scale score from baseline to 12 months. Three hundred seventy-one subjects were included in the 1-year efficacy analysis. Subjects treated with rasagiline, 2 mg/d, for 1 year had a 2.29-unit smaller increase in mean adjusted total Unified Parkinson's Disease Rating Scale score compared with subjects treated with placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months (P =.01). The mean adjusted difference between the placebo/rasagiline, 2 mg/d, group and those receiving rasagiline, 1 mg/d, for 1 year was -1.82 unit on the Unified Parkinson's Disease Rating Scale score (P =.05). Subjects treated with rasagiline, 2 and 1 mg/d, for 12 months showed less functional decline than subjects whose treatment was delayed for 6 months.

  20. Investigations of remote sensing techniques for early detection of Dutch elm disease

    NASA Technical Reports Server (NTRS)

    Hammerschlag, R. S.; Sopstyle, W. J.

    1975-01-01

    Several forms of aerial photography were pursued in quest of a technique which could provide early detection of Dutch elm disease. The two most promising techniques tested were multispectral photography with object enhancement and biband ratioing coupled with scanning microdensitometry. For practical purposes the multispectral system has the advantage of providing a readily interpretable image in a relatively short time. Laboratory studies indicated that less emphasis should be placed on the use of a red filter or the near infrared beyond 750 mm for early detection of stress within a single plant species. Color infrared film would be optimal when used for a long term detection of loss of plant vigor which results in a physical change in a plant canopy, but should find minimal practicality for early detection of specific sources of plant stress such as Dutch elm disease. Considerable discretion should be used when interpreting imagery on copy film because of loss of resolution and color definition.

  1. Early Motor Unit Disease Masquerading as Psychogenic Breathy Dysphonia: A Clinical Case Presentation

    ERIC Educational Resources Information Center

    Aronson, Arnold E.

    1971-01-01

    Presented is a study of a 20-year-old girl with mild, breathy dysphonia, previously diagnosed as psychogenic. In actuality, her voice change was a sign of early myasthenia gravis. It is pointed out that voice changes can be a first and only sign of early neurologic disease. (Author/KW)

  2. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    PubMed

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

    PubMed

    Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

    2014-07-01

    Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Changes in insomnia subtypes in early Parkinson disease.

    PubMed

    Tholfsen, Lena K; Larsen, Jan P; Schulz, Jörn; Tysnes, Ole-Bjørn; Gjerstad, Michaela D

    2017-01-24

    To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD. © 2016 American Academy of Neurology.

  5. Early neurovascular dysfunction in a transgenic rat model of Alzheimer's disease.

    PubMed

    Joo, Illsung L; Lai, Aaron Y; Bazzigaluppi, Paolo; Koletar, Margaret M; Dorr, Adrienne; Brown, Mary E; Thomason, Lynsie A M; Sled, John G; McLaurin, JoAnne; Stefanovic, Bojana

    2017-04-12

    Alzheimer's disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans.

  6. Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

    PubMed Central

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-01-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

  7. Biomechanical and morphological multi-parameter photoacoustic endoscope for identification of early esophageal disease

    NASA Astrophysics Data System (ADS)

    Jin, Dayang; Yang, Fen; Chen, Zhongjiang; Yang, Sihua; Xing, Da

    2017-09-01

    The combination of phase-sensitive photoacoustic (PA) imaging of tissue viscoelasticity with the esophagus-adaptive PA endoscope (PAE) technique allows the characterization of the biomechanical and morphological changes in the early stage of esophageal disease with high accuracy. In this system, the tissue biomechanics and morphology are obtained by detecting the PA phase and PA amplitude information, respectively. The PAE has a transverse resolution of approximately 37 μm and an outer diameter of 1.2 mm, which is suitable for detecting rabbit esophagus. Here, an in-situ biomechanical and morphological study of normal and diseased rabbit esophagus (tumors of esophagus and reflux esophagitis) was performed. The in-situ findings were highly consistent with those observed by histology. In summary, we demonstrated the potential application of PAE for early clinical detection of esophageal diseases.

  8. Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

    PubMed

    Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

    2014-06-01

    Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. A SHORT-TERM REPRODUCTIVE TEST WITH THE FATHEAD MINNOW (PIMEPHALES PROMELAS)

    EPA Science Inventory

    Due to the time and expense associated with full life-cycle testing, most current toxicity tests with fish do not explicity consider reproductive output as an endpoint but, rather, focus on early life-stage survival and development. However, there are classes of chemicals that co...

  10. A SHORT-TERM REPRODUCTION TEST WITH THE FATHEAD MINNOW (PIMEPHALES PROMELAS): L METHODS DESCRIPTION

    EPA Science Inventory

    Due to the time and expense associated with full life-cycle testing, most current toxicity tests with fish do not explicity consider reproductive output as an endpoint but, rather, focus on early life-stage survival and development. However, there are classes of chemicals that co...

  11. RED Alert – Early warning or detection of global re-emerging infectious disease (RED)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Deshpande, Alina

    This is the PDF of a presentation for a webinar given by Los Alamos National Laboratory (LANL) on the early warning or detection of global re-emerging infectious disease (RED). First, there is an overview of LANL biosurveillance tools. Then, information is given about RED Alert. Next, a demonstration is given of a component prototype. RED Alert is an analysis tool that can provide early warning or detection of the re-emergence of an infectious disease at the global level, but through a local lens.

  12. Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

    PubMed Central

    Hanson, M. A.; Gluckman, P. D.

    2014-01-01

    Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

  13. The management of patients with early Parkinson's disease.

    PubMed

    Rascol, O; Payoux, P; Ferreira, J; Brefel-Courbon, C

    2002-10-01

    A major problem in the management of early Parkinson's disease is to choose the first medication to prescribe. This decision should rely on the level of available clinical evidence, largely based, at least for efficacy, on the results of randomised clinical trials. Safety and costs are also crucial to consider. Other factors like for example pathophysiological concepts, individual experience, marketing pressure, socio-economical environment, patients needs and expectations have, however, also their own influence. Levodopa is efficacious and cheap, but induces long-term motor complications. The early use of dopamine agonists is more and more frequently promoted, because large prospective L-dopa-controlled trials demonstrated that this strategy reduces the risk of such long-term complications. Integrating individual clinical expertise to the best available external clinical evidence (evidence-based medicine) is the best strategy in making decisions about the care of individual patients. Copyright 2002 Elsevier Science Ltd.

  14. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    PubMed

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

  15. Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience.

    PubMed

    Parashos, Sotirios A; Luo, Sheng; Biglan, Kevin M; Bodis-Wollner, Ivan; He, Bo; Liang, Grace S; Ross, G Webster; Tilley, Barbara C; Shulman, Lisa M

    2014-06-01

    Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD. Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials. Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95

  16. Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker discovery

    PubMed Central

    Lin, Xiangmin; Shi, Min; Gunasingh Masilamoni, Jeyaraj; Dator, Romel; Movius, James; Aro, Patrick; Smith, Yoland; Zhang, Jing

    2015-01-01

    Identification of reliable and robust biomarkers is crucial to enable early diagnosis of Parkinson disease (PD) and monitoring disease progression. While imperfect, the slow, chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced non-human primate animal model system of parkinsonism is an abundant source of pre-motor or early stage PD biomarker discovery. Here, we present a study of a MPTP rhesus monkey model of PD that utilizes complementary quantitative iTRAQ-based proteomic, glycoproteomics and phosphoproteomics approaches. We compared the glycoprotein, non-glycoprotein, and phosphoprotein profiles in the putamen of asymptomatic and symptomatic MPTP-treated monkeys as well as saline injected controls. We identified 86 glycoproteins, 163 non-glycoproteins, and 71 phosphoproteins differentially expressed in the MPTP-treated groups. Functional analysis of the data sets inferred the biological processes and pathways that link to neurodegeneration in PD and related disorders. Several potential biomarkers identified in this study have already been translated for their usefulness in PD diagnosis in human subjects and further validation investigations are currently under way. In addition to providing potential early PD biomarkers, this comprehensive quantitative proteomic study may also shed insights regarding the mechanisms underlying early PD development. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology. PMID:25617661

  17. Organochlorine pesticides and thiamine in eggs of largemouth bass and American alligators and their relationship with early life-stage mortality

    USGS Publications Warehouse

    Sepulveda, M.S.; Wiebe, J.J.; Honeyfield, D.C.; Rauschenberger, H.R.; Hinterkopf, J.P.; Johnson, W.E.; Gross, T.S.

    2004-01-01

    Thiamine deficiency has been linked to early mortality syndrome in salmonids in the Great Lakes. This study was conducted to compare thiamine concentrations in American alligators (Alligator mississippiensis) and Florida largemouth bass (Micropterus salmoides floridanus) eggs from sites with high embryo mortality and high exposure to organochlorine pesticides (OCPs) (Lakes Apopka and Griffin, and Emeralda Marsh, Florida, USA) to those from sites that have historically exhibited low embryo mortality and low OCPs (Lakes Woodruff and Orange, Florida). During June-July 2000, 20 alligator clutches were collected from these sites, artificially incubated, and monitored for embryo mortality. Thiamine and OCPs were measured in one egg/clutch. During February 2002, 10 adult female bass were collected from Emeralda Marsh and Lake Woodruff and mature ovaries analyzed for thiamine and OCP concentrations. Although ovaries from the Emeralda Marsh bass contained almost 1,000-fold more OCPs compared with the reference site, Lake Woodruff, there were no differences in thiamine concentrations between sites (11,710 vs. 11,857 pmol/g). In contrast, alligator eggs from the reference site had five times the amount of thiamine compared with the contaminated sites (3,123 vs. 617 pmol/g). Similarly, clutches with > 55% hatch rates had significantly higher concentrations of thiamine compared with clutches with <54% hatch rates (1,119 vs. 201 pmol/g). These results suggest that thiamine deficiency might be playing an important role in alligator embryo survival but not in reproductive failure and recruitment of largemouth bass. The cause(s) of this thiamine deficiency are unknown but might be related to differences in the nutritional value of prey items across the sites studied and/or to the presence of high concentration of contaminants in eggs. ?? Wildlife Disease Association 2004.

  18. Verbal and visual memory in patients with early Parkinson's disease: effect of levodopa.

    PubMed

    Singh, Sumit; Behari, Madhuri

    2006-03-01

    The effect of initiation of levodopa therapy on the memory functions in patients with Parkinson's disease remains poorly understood. To evaluate the effect of initiation of levodopa therapy on memory, in patients with early Parkinson's disease. Prospective case control study. Seventeen patients with early Parkinson's disease were evaluated for verbal memory using Rey's auditory verbal learning test, and visual memory using the Benton's visual retention test and Form sequence learning test. UPDRS scores, Hoehn and Yahr's Staging and Schwab and England scores of Activities of daily living. Hamilton's depression rating scale and MMSE were also evaluated. Six controls were also evaluated according to similar study protocol. Levodopa was then prescribed to the cases. Same tests were repeated on all the subjects after 12 weeks. The mean age of the patients was 59.8 (+ 12.9 yrs); mean disease duration of 3.26 (+ 2.06 yrs). The mean UPDRS scores of patients were 36.52 (+ 15.84). Controls were of a similar age and sex distribution. A statistically significant improvement in the scores on the UPDRS, Hamilton's depression scale, Schwab and England scale, and a statistically significant deterioration in the scores of visual memory was observed in patients with PD after starting levodopa, as compared to their baseline scores. There was no correlation between degree of deterioration and the dose of levodopa. Initiation of levodopa therapy in patients with early and stable Parkinson's disease is associated with deterioration in visual memory functions, with relative preservation of the verbal memory.

  19. Are Upper-Body Axial Symptoms a Feature of Early Parkinson’s Disease?

    PubMed Central

    Moreau, Caroline; Baille, Guillaume; Delval, Arnaud; Tard, Céline; Perez, Thierry; Danel-Buhl, Nicolas; Seguy, David; Labreuche, Julien; Duhamel, Alain; Delliaux, Marie; Dujardin, Kathy; Defebvre, Luc

    2016-01-01

    Background Axial disorders are considered to appear late in the course of Parkinson’s disease (PD). The associated impact on quality of life (QoL) and survival and the lack of an effective treatment mean that understanding and treating axial disorders is a key challenge. However, upper-body axial disorders (namely dysarthria, swallowing and breathing disorders) have never been prospectively assessed in early-stage PD patients. Objectives To characterize upper-body axial symptoms and QoL in consecutive patients with early-stage PD. Methods We prospectively enrolled 66 consecutive patients with early-stage PD (less than 3 years of disease progression) and assessed dysarthria, dysphagia and respiratory function (relative to 36 controls) using both objective and patient-reported outcomes. Results The mean disease duration was 1.26 years and the mean UPDRS motor score was 19.4 out of 108. 74% of the patients presented slight dysarthria (primarily dysprosodia). Men appeared to be more severely affected (i.e. dysphonia). This dysfunction was strongly correlated with low swallowing speed (despite the absence of complaints about dysphagia), respiratory insufficiency and poor QoL. Videofluorography showed that oral-phase swallowing disorders affected 60% of the 31 tested patients and that pharyngeal-phase disorders affected 21%. 24% of the patients reported occasional dyspnea, which was correlated with anxiety in women but not in men. Marked diaphragmatic dysfunction was suspected in 42% of the patients (predominantly in men). Conclusion Upper body axial symptoms were frequent in men with early-stage PD, whereas women presented worst non-motor impairments. New assessment methods are required because currently available tools do not reliably detect these upper-body axial disorders. PMID:27654040

  20. YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease.

    PubMed

    Ghilan, Mohamed; Bostrom, Crystal A; Hryciw, Brett N; Simpson, Jessica M; Christie, Brian R; Gil-Mohapel, Joana

    2014-09-18

    Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the protein huntingtin. The disease progresses over decades, but often patients develop cognitive impairments that precede the onset of the classical motor symptoms. Similar to the disease progression in humans, the yeast artificial chromosome (YAC) 128 HD mouse model also exhibits cognitive dysfunction that precedes the onset of the neuropathological and motor impairments characteristic of HD. Thus, the purpose of this study was to evaluate whether short- and long-term synaptic plasticity in the hippocampus, two related biological models of learning and memory processes, were altered in YAC128 mice in early stages of disease progression. We show that the YAC128 hippocampal dentate gyrus (DG) displays marked reductions in paired-pulse depression both at 3 and 6 months of age. In addition, significantly enhanced post-tetanic and short-term potentiation are apparent in YAC128 mice after high-frequency stimulation at this time. Early and late forms of long-term plasticity were not altered at this stage. Together these findings indicate that there may be elevated neurotransmitter release in response to synaptic stimulation in YAC128 mice during the initial phase of disease progression. These abnormalities in short-term plasticity detected at this stage in YAC128 HD transgenic mice indicate that aberrant information processing at the level of the synapses may contribute, at least in part, to the early onset of cognitive deficits that are characteristic of this devastating neurodegenerative disorder. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mullan, M.; Bennett, C.; Figueredo, C.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onsetmore » disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.« less

  2. Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

    PubMed Central

    Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

    2016-01-01

    Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced

  3. Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.

    PubMed

    Conrado, Daniela J; Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A; Kern, Volker D; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T; Romero, Klaus

    2018-01-01

    Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  4. Assessing Marine Species Exposure to Ocean Acidification

    NASA Astrophysics Data System (ADS)

    Jewett, E.; Busch, S.; McElhany, P.; Gledhill, D. K.; Milke, L. M.; Wieczorek, D.

    2016-02-01

    Assessing the vulnerability of society to ocean acidification (OA) demands an understanding of both the sensitivity of economically important species together with an organism's exposure to potentially harmful carbonate chemistry conditions. However, research has revealed that sensitivity to OA is frequently life-stage dependent and the environmental conditions experienced by a marine organism often vary with life-stage. Enhancing the development of a National Ocean Acidification Observing Network (NOA-ON) and establishing appropriate treatment conditions for experimental studies requires careful consideration of where the vulnerable life-stages of an organism reside in space (e.g., estuary versus oceanic), depth (e.g., surface mixed layer versus benthos), and time (e.g., diel vertical migration, seasonality of the chemical environment within the context of an organism life cycle). Few studies have explicitly attempted to document carbonate chemistry dynamics specific to a given organism's life-cycle. Here we estimate carbonate dynamics in terms of aragonite saturation state range and variability within the U.S. Northeast and West Coast through the application of NOAA's NOA-ON assets mapped out with respect to the life stages of economically important species within those regions. Two economically important species will be considered for which the life-cycles are well known along with the sensitivities to OA for early life-stages: Atlantic Surf Clam in the northeast and Dungeness Crab of the northwest coast of the U.S. Other species may also be considered.

  5. Early-Life Toxic Insults and Onset of Sporadic Neurodegenerative Diseases-an Overview of Experimental Studies.

    PubMed

    Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma

    2016-01-01

    The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies.

  6. Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease.

    PubMed

    Kalliokoski, Suvi; Caja, Sergio; Frias, Rafael; Laurila, Kaija; Koskinen, Outi; Niemelä, Onni; Mäki, Markku; Kaukinen, Katri; Korponay-Szabó, Ilma R; Lindfors, Katri

    2015-01-01

    Typical features of celiac disease are small-bowel villus atrophy, crypt hyperplasia, and inflammation which develop gradually concomitant with ingestion of gluten. In addition, patients have anti-transglutaminase 2 (TG2) autoantibodies in their serum and tissues. The aim of this study was to establish whether celiac disease can be passively transferred to mice by serum or immunoglobulins. Serum aliquots or purified immunoglobulins (Ig) were intraperitoneally injected into Hsd:Athymic Nude-Foxn1nu mice for 8 or 27 days. As mice do not have proper IgA transport from peritoneum to blood, sera with a high content of IgG class anti-TG2 antibodies from untreated IgA-deficient celiac patients were used. Mouse sera were tested for celiac disease-specific autoantibodies, and several tissues were analyzed for autoantibody deposits targeted to TG2. Morphological assessment was made of the murine small intestinal mucosa. Injection of celiac disease patient sera or total IgG led to a significant delay in weight gain and mild diarrhea in a subset of mice. The mice injected with celiac patient sera or IgG had significantly decreased villus height crypt depth (Vh/CrD) ratios and celiac disease-specific autoantibody deposits targeted to TG2 in several tissues, including the small intestine. None of these features were observed in control mice. We conclude that administration of IgA-deficient celiac disease patient serum or total IgG induces both deterioration of the intestinal mucosa and clinical features of celiac disease in mice. The experimentally induced condition in the mice injected with patient serum or IgG resembles early developing celiac disease in humans. Celiac disease patient sera or total IgG was injected into athymic mice. A significant delay in weight gain and mild diarrhea was observed. Mice evinced significantly decreased villus height crypt depth ratios. Celiac disease-specific autoantibody deposits were present in several tissues. The condition in mice

  7. [Immune system aging rate in patients with early forms of chronic cerebrovascular diseases].

    PubMed

    Kochetkova, N G; Al'tman, D Sh; Teplova, S N

    2009-01-01

    Using the Bioage and Snake software the immune and cardiovascular system aging rate was diagnosed in patients having early forms of chronic cerebrovascular diseases (CCVD). The indicators of biological, cardiopulmonary and immunological age were studied in patients showing early symptoms of cerebrovascular insufficiency and dyscirculatory encephalopathy of the 1st stage. The rate of age-dependent physiological changes was diagnosed compared to general body aging rate. Some specific patterns of immune system aging were found in patients with early forms of CCVDs, the cardinal aging symptoms (heterotropia, heterochronia) were verified.

  8. Childhood developmental vulnerabilities associated with early life exposure to infectious and noninfectious diseases and maternal mental illness.

    PubMed

    Green, Melissa J; Kariuki, Maina; Dean, Kimberlie; Laurens, Kristin R; Tzoumakis, Stacy; Harris, Felicity; Carr, Vaughan J

    2017-12-26

    Fetal exposure to infectious and noninfectious diseases may influence early childhood developmental functioning, on the path to later mental illness. Here, we investigated the effects of in utero exposure to maternal infection and noninfectious diseases during pregnancy on offspring developmental vulnerabilities at age 5 years, in the context of estimated effects for early childhood exposures to infectious and noninfectious diseases and maternal mental illness. We used population data for 66,045 children from an intergenerational record linkage study (the New South Wales Child Development Study), for whom a cross-sectional assessment of five developmental competencies (physical, social, emotional, cognitive, and communication) was obtained at school entry, using the Australian Early Development Census (AEDC). Child and maternal exposures to infectious or noninfectious diseases were determined from the NSW Ministry of Health Admitted Patients Data Collection (APDC) and maternal mental illness exposure was derived from both APDC and Mental Health Ambulatory Data collections. Multinomial logistic regression analyses were used to examine unadjusted and adjusted associations between these physical and mental health exposures and child developmental vulnerabilities at age 5 years. Among the physical disease exposures, maternal infectious diseases during pregnancy and early childhood infection conferred the largest associations with developmental vulnerabilities at age 5 years; maternal noninfectious illness during pregnancy also retained small but significant associations with developmental vulnerabilities even when adjusted for other physical and mental illness exposures and covariates known to be associated with early childhood development (e.g., child's sex, socioeconomic disadvantage, young maternal age, prenatal smoking). Among all exposures examined, maternal mental illness first diagnosed prior to childbirth conferred the greatest odds of developmental

  9. Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease.

    PubMed

    Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J

    2016-01-01

    Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task.

  10. 40 CFR 132.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Definitions. 132.2 Section 132.2... acceptable early life-stage tests. Stream design flow is the stream flow that represents critical conditions... used in operationally deriving criteria from experimental data to account for the quality or quantity...

  11. Early life programming and the risk of non-alcoholic fatty liver disease.

    PubMed

    Lynch, C; Chan, C S; Drake, A J

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

  12. Allergic Diseases and Internalizing Behaviors in Early Childhood

    PubMed Central

    LeMasters, Grace K.; Levin, Linda; Rothenberg, Marc E.; Assa'ad, Amal H.; Newman, Nicholas; Bernstein, David; Khurana-Hershey, Gurjit; Lockey, James E.; Ryan, Patrick H.

    2016-01-01

    BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. RESULTS: The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8–5.8), anxiety (aOR: 2.0; 95% CI: 1.2–3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7–6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2–6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7–7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0–9.2) at age 4 had dose-dependent associations with internalizing scores. CONCLUSIONS: Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores. PMID:26715608

  13. Allergic Diseases and Internalizing Behaviors in Early Childhood.

    PubMed

    Nanda, Maya K; LeMasters, Grace K; Levin, Linda; Rothenberg, Marc E; Assa'ad, Amal H; Newman, Nicholas; Bernstein, David; Khurana-Hershey, Gurjit; Lockey, James E; Ryan, Patrick H

    2016-01-01

    The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8-5.8), anxiety (aOR: 2.0; 95% CI: 1.2-3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7-6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2-6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7-7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0-9.2) at age 4 had dose-dependent associations with internalizing scores. Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores. Copyright © 2016 by the American Academy of Pediatrics.

  14. Early neurovascular dysfunction in a transgenic rat model of Alzheimer’s disease

    PubMed Central

    Joo, Illsung L.; Lai, Aaron Y.; Bazzigaluppi, Paolo; Koletar, Margaret M.; Dorr, Adrienne; Brown, Mary E.; Thomason, Lynsie A. M.; Sled, John G.; McLaurin, JoAnne; Stefanovic, Bojana

    2017-01-01

    Alzheimer’s disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans. PMID:28401931

  15. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

    PubMed Central

    Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

    2014-01-01

    Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

  16. Knowledge-based compact disease models identify new molecular players contributing to early-stage Alzheimer’s disease

    PubMed Central

    2013-01-01

    Background High-throughput profiling of human tissues typically yield as results the gene lists comprised of a mix of relevant molecular entities with multiple false positives that obstruct the translation of such results into mechanistic hypotheses. From general probabilistic considerations, gene lists distilled for the mechanistically relevant components can be far more useful for subsequent experimental design or data interpretation. Results The input candidate gene lists were processed into different tiers of evidence consistency established by enrichment analysis across subsets of the same experiments and across different experiments and platforms. The cut-offs were established empirically through ontological and semantic enrichment; resultant shortened gene list was re-expanded by Ingenuity Pathway Assistant tool. The resulting sub-networks provided the basis for generating mechanistic hypotheses that were partially validated by literature search. This approach differs from previous consistency-based studies in that the cut-off on the Receiver Operating Characteristic of the true-false separation process is optimized by flexible selection of the consistency building procedure. The gene list distilled by this analytic technique and its network representation were termed Compact Disease Model (CDM). Here we present the CDM signature for the study of early-stage Alzheimer’s disease. The integrated analysis of this gene signature allowed us to identify the protein traffic vesicles as prominent players in the pathogenesis of Alzheimer’s. Considering the distances and complexity of protein trafficking in neurons, it is plausible that spontaneous protein misfolding along with a shortage of growth stimulation result in neurodegeneration. Several potentially overlapping scenarios of early-stage Alzheimer pathogenesis have been discussed, with an emphasis on the protective effects of AT-1 mediated antihypertensive response on cytoskeleton remodeling, along with

  17. Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

    PubMed

    Shemenski, Justin

    2016-04-09

    Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most common vector-borne illness in the United States. It is a complex disease which may affect the skin, joints, heart, eyes, and central nervous system. Prompt diagnosis and treatment is curative in most instances. However, a significant percentage of patients experience ongoing symptoms after treatment. Currently, there is much controversy regarding the diagnosis, pathophysiology, and treatment of Lyme disease. Pathogen persistence despite treatment lies at the heart of this debate. Many believe that the ongoing symptoms are due to factors such as autoimmunity or permanent damage that is incurred during the active infection. However, there is an emerging school of thought that states that ongoing symptoms are due to a persistent infection that is able to survive both the immune response and antibiotic therapy. Numerous studies have shown that Bb can indeed persist within the host despite treatment and several mechanisms have been proposed to explain Bb's persistence capabilities. These include: polymorphism, antigenic variance, biofilm formation, persister cells, and immunomodulation. There is evidence that Bb is able to alter cytokine profiles within the host which may allow the organism to survive the immune response. This immunomodulation follows a pattern of T-helper 1 (TH1) suppression in favor of T-helper 2 (TH2) processes. In contrast, it has been shown that the optimal immune response to Bb infection involves an early, robust TH1 response and a later conversion to TH2 dominance once the infection is controlled or cleared. It has been proposed that a reconstitution of proper immune-competency in the infected host may improve clinical outcomes in Lyme disease. Cimetidine (CIM) is an over-the-counter histamine-2 (H2) antagonist that is primarily used to lower acid secretions in the stomach. T-regulatory (Treg) cells also possess the H2 receptor, which has spurred interest in CIM as a

  18. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study.

    PubMed

    2002-12-01

    Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. Academically based movement disorders clinics. Patients with early PD not requiring dopaminergic therapy (n = 404). Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scal score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, -5.66 to -2.73 units; P<.001) and -3.56 units comparing a 2-mg dosage and placebo (95% confidence interval, -5.04 to -2.08 units; P<.001). There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups. Rasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.

  19. PGC-1α, A Potential Therapeutic Target for Early Intervention in Parkinson’s Disease

    PubMed Central

    Zheng, Bin; Liao, Zhixiang; Locascio, Joseph J.; Lesniak, Kristen A.; Roderick, Sarah S.; Watt, Marla L.; Eklund, Aron C.; Zhang-James, Yanli; Kim, Peter D.; Hauser, Michael A.; Grünblatt, Edna; Moran, Linda B.; Mandel, Silvia A.; Riederer, Peter; Miller, Renee M.; Federoff, Howard J.; Wüllner, Ullrich; Papapetropoulos, Spyridon; Youdim, Moussa B.; Cantuti-Castelvetri, Ippolita; Young, Anne B.; Vance, Jeffery M.; Davis, Richard L.; Hedreen, John C.; Adler, Charles H.; Beach, Thomas G.; Graeber, Manuel B.; Middleton, Frank A.; Rochet, Jean-Christophe; Scherzer, Clemens R.

    2011-01-01

    Parkinson’s disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson’s and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene sets with previously unknown associations with Parkinson’s disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed in response to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) are underexpressed in Parkinson’s disease patients. Activation of PGC-1α results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced by mutant α-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson’s disease identifies PGC-1α as a potential therapeutic target for early intervention. PMID:20926834

  20. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    PubMed

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  1. Multidisciplinary strategies in the management of early chronic kidney disease.

    PubMed

    Martínez-Ramírez, Héctor R; Cortés-Sanabria, Laura; Rojas-Campos, Enrique; Hernández-Herrera, Aurora; Cueto-Manzano, Alfonso M

    2013-11-01

    Chronic kidney disease (CKD) is a worldwide epidemic especially in developing countries, with clear deficiencies in identification and treatment. Better care of CKD requires more than only economic resources, utilization of health research in policy-making and health systems changes that produce better outcomes. A multidisciplinary approach may facilitate and improve management of patients from early CKD in the primary health-care setting. This approach is a strategy for improving comprehensive care, initiating and maintaining healthy behaviors, promoting teamwork, eliminating barriers to achieve goals and improving the processes of care. A multidisciplinary intervention may include educational processes guided by health professional, use of self-help groups and the development of a CKD management plan. The complex and fragmented care management of patients with CKD, associated with poor outcome, enhances the importance of implementing a multidisciplinary approach in the management of this disease from the early stages. Multidisciplinary strategies should focus on the needs of patients (to increase their empowerment) and should be adapted to the resources and health systems prevailing in each country; its systematic implementation can help to improve patient care and slow the progression of CKD. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  2. Is epigenetics an important link between early life events and adult disease?

    USDA-ARS?s Scientific Manuscript database

    Epigenetic mechanisms provide one potential explanation for how environmental influences in early life cause long-term changes in chronic disease susceptibility. Whereas epigenetic dysregulation is increasingly implicated in various rare developmental syndromes and cancer, the role of epigenetics in...

  3. Early Alzheimer's Disease Neuropathology Detected by Proton MR Spectroscopy

    PubMed Central

    Murray, Melissa E.; Przybelski, Scott A.; Lesnick, Timothy G.; Liesinger, Amanda M.; Spychalla, Anthony; Zhang, Bing; Gunter, Jeffrey L.; Parisi, Joseph E.; Boeve, Bradley F.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Dickson, Dennis W.

    2014-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is sensitive to early neurodegenerative processes associated with Alzheimer's disease (AD). Although 1H-MRS metabolite ratios of N-acetyl aspartate (NAA)/creatine (Cr), NAA/myoinositol (mI), and mI/Cr measured in the posterior cingulate gyrus reveal evidence of disease progression in AD, pathologic underpinnings of the 1H-MRS metabolite changes in AD are unknown. Pathologically diagnosed human cases ranging from no likelihood to high likelihood AD (n = 41, 16 females and 25 males) who underwent antemortem 1H-MRS of the posterior cingulate gyrus at 3 tesla were included in this study. Immunohistochemical evaluation was performed on the posterior cingulate gyrus using antibodies to synaptic vesicles, hyperphosphorylated tau (pTau), neurofibrillary tangle conformational-epitope (cNFT), amyloid-β, astrocytes, and microglia. The slides were digitally analyzed using Aperio software, which allows neuropathologic quantification in the posterior cingulate gray matter. MRS and pathology associations were adjusted for time from scan to death. Significant associations across AD and control subjects were found between reduced synaptic immunoreactivity and both NAA/Cr and NAA/mI in the posterior cingulate gyrus. Higher pTau burden was associated with lower NAA/Cr and NAA/mI. Higher amyloid-β burden was associated with elevated mI/Cr and lower NAA/mI ratios, but not with NAA/Cr. 1H-MRS metabolite levels reveal early neurodegenerative changes associated with AD pathology. Our findings support the hypothesis that a decrease in NAA/Cr is associated with loss of synapses and early pTau pathology, but not with amyloid-β or later accumulation of cNFT pathology in the posterior cingulate gyrus. In addition, elevation of mI/Cr is associated with the occurrence of amyloid-β plaques in AD. PMID:25471565

  4. Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

    PubMed

    Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

    2018-02-07

    Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks

  5. Low-grade disease activity in early life precedes childhood asthma and allergy.

    PubMed

    Chawes, Bo Lund Krogsgaard

    2016-08-01

    Asthma and allergies are today the most common chronic diseases in children and the leading causes of school absences, chronic medication usage, emergency department visits and hospitalizations, which affect all members of the family and represent a significant societal and scientific challenge. These highly prevalent disorders are thought to originate from immune distortion in early childhood, but the etiology and heterogeneity of the disease mechanisms are not understood, which hampers preventive initiatives and makes treatment inadequate. The objective of this thesis is to investigate the presence of an early life disease activity prior to clinical symptoms to understand the anteceding pathophysiological steps towards childhood asthma and allergy. The thesis is built on seven studies from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) birth cohort examining biomarkers of disease activity in 411 asymptomatic neonates in cord blood (I-II), urine (III), exhaled breath (IV-V) and infant lung function (VI-VII) in relation to the subsequent development of asthma and allergy during the first seven years of life. In papers I-II, we studied cord blood chemokines and 25(OH)-vitamin D, which represent a proxy of the inborn immature immune system, the intrauterine milieu, and the maternal immune health during pregnancy. High levels of the Th2-related chemokine CCL22 and high CCL22/CXCL11 ratio were positively correlated with total IgE level during preschool age (II). This suggests an inborn Th2 skewing of the immune system in healthy newborns subsequently developing elevated total IgE antibodies, which is considered to increase the risk of asthma and allergies later in life. Additionally, deficient cord blood 25(OH)-vitamin D levels were associated with a 2.7-fold increased risk of recurrent wheeze at age 0-7 years (I). Together, these findings support the concept that early life immune programming in the pre-symptomatic era plays an essential role

  6. Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.

    PubMed

    Snowdon, D A; Kemper, S J; Mortimer, J A; Greiner, L H; Wekstein, D R; Markesbery, W R

    1996-02-21

    To determine if linguistic ability in early life is associated with cognitive function and Alzheimer's disease in late life. Two measures of linguistic ability in early life, idea density and grammatical complexity, were derived from autobiographies written at a mean age of 22 years. Approximately 58 years later, the women who wrote these autobiographies participated in an assessment of cognitive function, and those who subsequently died were evaluated neuropathologically. Convents in the United States participating in the Nun Study; primarily convents in the Milwaukee, Wis, area. Cognitive function was investigated in 93 participants who were aged 75 to 95 years at the time of their assessments, and Alzheimer's disease was investigated in the 14 participants who died at 79 to 96 years of age. Seven neuropsychological tests and neuropathologically confirmed Alzheimer's disease. Low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Low idea density in early life had stronger and more consistent associations with poor cognitive function than did low grammatical complexity. Among the 14 sisters who died, neuropathologically confirmed Alzheimer's disease was present in all of those with low idea density in early life and in none of those with high idea density. Low linguistic ability in early life was a strong predictor of poor cognitive function and Alzheimer's disease in late life.

  7. Molecular genetics of early-onset Alzheimer's disease revisited.

    PubMed

    Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

    2016-06-01

    As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Deep Brain Stimulation for Early Stage Parkinson's Disease: An Illustrative Case

    PubMed Central

    Gill, Chandler E.; Allen, Laura A.; Konrad, Peter E.; Davis, Thomas L.; Bliton, Mark J.; Finder, Stuart G.; Tramontana, Michael G.; Kao, C. Chris; Remple, Michael S.; Bradenham, Courtney H.; Charles, P. David

    2011-01-01

    Objectives Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective intervention in advanced Parkinson's Disease (PD), but its efficacy and safety in early PD are unknown. Our team is conducting a randomized pilot trial investigating DBS in early PD. This report describes one participant who received bilateral STN-DBS. Materials/Methods Thirty subjects have been randomized to either optimal drug therapy (ODT) or DBS + ODT. Microelectrode recordings from the STN and substantia nigra (SN) are collected at implantation. The Unified Parkinson's Disease Rating Scale Motor Subscale (UPDRS-III) is administered in the ON and OFF states semi-annually and neuropsychological function and quality of life are assessed annually. We describe a 54-year-old man with a two-year history of PD who was randomized to DBS + ODT and followed for two years. Results The subject showed a lower STN to SN ratio of neuronal activity than advanced PD patients, and higher firing rate than non-PD patients. The subject's ON total UPDRS and UPDRS-III scores improved during the two-year follow-up, while his OFF UPDRS-III score and levodopa equivalent daily dose (LEDD) increased. Quality of life, verbal fluency and verbal learning improved. He did not experience any serious adverse events. Conclusions This report details the first successful application of bilateral STN DBS for early stage PD during a clinical trial. PMID:21939467

  9. Lifestyle Knowledge and Preferences in Preschool Children: Evaluation of the "Get up and Grow" Healthy Lifestyle Education Programme

    ERIC Educational Resources Information Center

    Wiseman, Nicola; Harris, Neil; Lee, Patricia

    2016-01-01

    Objective: Early childhood is considered a window of opportunity for lifestyle interventions, as this is a critical life-stage at which children accumulate knowledge and skills around behaviours such as eating and physical activity. This study examined how exposure to a settings-based healthy lifestyle programme influences knowledge and preference…

  10. Antibiotic Use in Early Life, Rural Residence, and Allergic Diseases in Argentinean Children.

    PubMed

    Han, Yueh-Ying; Forno, Erick; Badellino, Héctor A; Celedón, Juan C

    Little is known about differential effects of antibiotic use on allergic diseases in rural versus urban environments. To examine whether area of residence in the first year of life modifies the relation between antibiotic use in early life and allergic diseases during childhood. Cross-sectional study of allergic diseases in 1517 children (ages 6-7 years) attending 101 schools in urban and rural areas of San Francisco (Córdoba, Argentina). Current asthma, wheeze, and allergic rhinoconjunctivitis were defined on the basis of responses to a validated questionnaire from the International Study of Asthma and Allergies in Childhood. Multivariate logistic regression was used for the analysis of antibiotic use and allergic diseases. After adjustment for paracetamol use, bronchiolitis, and other covariates, antibiotic use in the first year of life was associated with increased odds of current wheeze (odds ratio [OR], 1.8; 95% CI, 1.3-2.6) and allergic rhinoconjunctivitis (OR, 1.9; 95% CI, 1.3-2.7). After stratification by area of residence, antibiotic use was associated with current wheeze (OR, 2.4; 95% CI, 1.5-4.0) and allergic rhinoconjunctivitis (OR, 2.1; 95% CI, 1.3-3.4) among children who lived in an urban area in their first year of life, but not among those who lived in a rural area in their first year of life. Early-life antibiotic use is associated with current wheeze and allergic rhinoconjunctivitis in Argentinean children who lived in urban areas during their first year of life. Exposure to a rural environment early in life may protect against the adverse effects of antibiotics on atopic diseases in children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. How to select a proper early warning threshold to detect infectious disease outbreaks based on the China infectious disease automated alert and response system (CIDARS).

    PubMed

    Wang, Ruiping; Jiang, Yonggen; Michael, Engelgau; Zhao, Genming

    2017-06-12

    China Centre for Diseases Control and Prevention (CDC) developed the China Infectious Disease Automated Alert and Response System (CIDARS) in 2005. The CIDARS was used to strengthen infectious disease surveillance and aid in the early warning of outbreak. The CIDARS has been integrated into the routine outbreak monitoring efforts of the CDC at all levels in China. Early warning threshold is crucial for outbreak detection in the CIDARS, but CDCs at all level are currently using thresholds recommended by the China CDC, and these recommended thresholds have recognized limitations. Our study therefore seeks to explore an operational method to select the proper early warning threshold according to the epidemic features of local infectious diseases. The data used in this study were extracted from the web-based Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS), and data for infectious disease cases were organized by calendar week (1-52) and year (2009-2015) in Excel format; Px was calculated using a percentile-based moving window (moving window [5 week*5 year], x), where x represents one of 12 centiles (0.40, 0.45, 0.50….0.95). Outbreak signals for the 12 Px were calculated using the moving percentile method (MPM) based on data from the CIDARS. When the outbreak signals generated by the 'mean + 2SD' gold standard were in line with a Px generated outbreak signal for each week during the year of 2014, this Px was then defined as the proper threshold for the infectious disease. Finally, the performance of new selected thresholds for each infectious disease was evaluated by simulated outbreak signals based on 2015 data. Six infectious diseases were selected in this study (chickenpox, mumps, hand foot and mouth diseases (HFMD), scarlet fever, influenza and rubella). Proper thresholds for chickenpox (P75), mumps (P80), influenza (P75), rubella (P45), HFMD (P75), and scarlet fever (P80) were identified. The selected proper thresholds for these

  12. EVALUATION OF SYMMETRIC DIMETHYLARGININE AS AN EARLY BIOMARKER OF CHRONIC KIDNEY DISEASE IN CAPTIVE CHEETAHS (ACINONYX JUBATUS).

    PubMed

    Lamglait, Benjamin; Vandenbunder-Beltrame, Marielle

    2017-09-01

    Symmetric dimethylarginine (SDMA) has been shown to be a valuable biomarker for early detection of chronic kidney disease (CKD) in canine and feline patients. Recognition of early (subclinical) kidney disease would be of value in cheetahs (Acinonyx jubatus) as prevalence of CKD is relatively high in this species in captivity. Fifty-eight banked serum and plasma samples from seven adult cheetahs that died of CKD were analyzed for creatinine, urea, and SDMA. A marked increase in SDMA was noted on five of the tested cheetahs earlier than the rise of serum creatinine and urea (estimated 8-35 mo; mean 21.4 mo; median 22 mo). SDMA appears as an early biomarker to evaluate renal function for the diagnosis of CKD in cheetahs regardless of the cause of this disease.

  13. Early Nutrition as a Major Determinant of 'Immune Health': Implications for Allergy, Obesity and Other Noncommunicable Diseases.

    PubMed

    Prescott, Susan L

    2016-01-01

    Early-life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. Dietary changes are at the center of the emerging epigenetic paradigms that underpin the rise in many modern inflammatory and metabolic diseases. There is growing evidence that exposures in pregnancy and the early postnatal period can modify gene expression and disease susceptibility. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients. Oligosaccharides (soluble fiber), antioxidants, polyunsaturated fatty acids, folate and other vitamins have documented effects on immune function as well as metabolism. Some have also been implicated in modified risk of allergic diseases in observational studies. Intervention studies are largely limited to trials with polyunsaturated fatty acids and oligosaccharides, showing preliminary but yet unconfirmed benefits in allergy prevention. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programming is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While an epigenetic mechanism provides a strong explanation of how nutritional exposures can affect fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function--including diet-induced changes in the microbiome. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures early in life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the

  14. Development and Operation of Space-Based Disease Early Warning Models

    NASA Astrophysics Data System (ADS)

    John, M. M.

    2010-12-01

    Millions of people die every year from preventable diseases such as malaria and cholera. Pandemics put the entire world population at risk and have the potential to kill thousands and cripple the global economy. In light of these dangers, it is fortunate that the data and imagery gathered by remote sensing satellites can be used to develop models that predict areas at risk for outbreaks. These warnings can help decision makers to distribute preventative medicine and other forms of aid to save lives. There are already many Earth observing satellites in orbit with the ability to provide data and imagery. Researchers have created a number of models based on this information, and some are being used in real-life situations. These capabilities should be further developed and supported by governments and international organizations to benefit as many people as possible. To understand the benefits and challenges of disease early warning models, it is useful to understand how they are developed. A number of steps must occur for satellite data and imagery to be used to prevent disease outbreaks; each requires a variety of inputs and may include a range of experts and stakeholders. This paper discusses the inputs, outputs, and basic processes involved in each of six main steps to developing models, including: identifying and validating links between a disease and environmental factors, creating and validating a software model to predict outbreaks, transitioning a model to operational use, using a model operationally, and taking action on the data provided by the model. The paper briefly overviews past research regarding the link between remote sensing data and disease, and identifies ongoing research in academic centers around the world. The activities of three currently operational models are discussed, including the U.S. Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS), NASA carries out its Malaria Modeling and Surveillance

  15. [Mutations of amyloid precursor protein in early-onset familial Alzheimer's disease].

    PubMed

    Naruse, S; Tsuji, S; Miyatake, T

    1992-09-01

    Genetic linkage studies of familial Alzheimer's disease (FAD) have suggested that some form of early-onset FAD is linked to proximal long arm of chromosome 21. It has been also suggested that some form of late-onset FAD is linked to long arm of chromosome 19. Goate et al have identified a mis-sense mutation (Val to Ile) in exon 17 of the amyloid precursor protein (APP) gene in 2 of 16 early-onset FAD families, and have shown that the FAD locus in an FAD family is tightly linked to the mis-sense mutation. To determine if the mis-sense mutation is observed in different ethnic origine, we have studied some early-onset FAD families. Two early-onset FAD families showed the existence of the mutation. As the mutation has been identified in different ethnic origine and the mutation has not been observed in normal individuals, it strengthen hypothesis that the mutation is pathogenic. Recently, Val to Phe and Val to Gly mutations have been also identified at the same codon (Codon 717) of the APP gene.

  16. Quantifying fish swimming behavior in response to acute exposure of aqueous copper using computer assisted video and digital image analysis

    USGS Publications Warehouse

    Calfee, Robin D.; Puglis, Holly J.; Little, Edward E.; Brumbaugh, William G.; Mebane, Christopher A.

    2016-01-01

    Behavioral responses of aquatic organisms to environmental contaminants can be precursors of other effects such as survival, growth, or reproduction. However, these responses may be subtle, and measurement can be challenging. Using juvenile white sturgeon (Acipenser transmontanus) with copper exposures, this paper illustrates techniques used for quantifying behavioral responses using computer assisted video and digital image analysis. In previous studies severe impairments in swimming behavior were observed among early life stage white sturgeon during acute and chronic exposures to copper. Sturgeon behavior was rapidly impaired and to the extent that survival in the field would be jeopardized, as fish would be swept downstream, or readily captured by predators. The objectives of this investigation were to illustrate protocols to quantify swimming activity during a series of acute copper exposures to determine time to effect during early lifestage development, and to understand the significance of these responses relative to survival of these vulnerable early lifestage fish. With mortality being on a time continuum, determining when copper first affects swimming ability helps us to understand the implications for population level effects. The techniques used are readily adaptable to experimental designs with other organisms and stressors.

  17. Quantifying Fish Swimming Behavior in Response to Acute Exposure of Aqueous Copper Using Computer Assisted Video and Digital Image Analysis

    PubMed Central

    Calfee, Robin D.; Puglis, Holly J.; Little, Edward E.; Brumbaugh, William G.; Mebane, Christopher A.

    2016-01-01

    Behavioral responses of aquatic organisms to environmental contaminants can be precursors of other effects such as survival, growth, or reproduction. However, these responses may be subtle, and measurement can be challenging. Using juvenile white sturgeon (Acipenser transmontanus) with copper exposures, this paper illustrates techniques used for quantifying behavioral responses using computer assisted video and digital image analysis. In previous studies severe impairments in swimming behavior were observed among early life stage white sturgeon during acute and chronic exposures to copper. Sturgeon behavior was rapidly impaired and to the extent that survival in the field would be jeopardized, as fish would be swept downstream, or readily captured by predators. The objectives of this investigation were to illustrate protocols to quantify swimming activity during a series of acute copper exposures to determine time to effect during early lifestage development, and to understand the significance of these responses relative to survival of these vulnerable early lifestage fish. With mortality being on a time continuum, determining when copper first affects swimming ability helps us to understand the implications for population level effects. The techniques used are readily adaptable to experimental designs with other organisms and stressors. PMID:26967350

  18. Gene-environment interaction in atopic diseases: a population-based twin study of early-life exposures.

    PubMed

    Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff; Kyvik, Kirsten Ohm; Skytthe, Axel; Backer, Vibeke; Bønnelykke, Klaus; Thomsen, Simon Francis

    2015-01-01

    The development of atopic diseases early in life suggests an important role of perinatal risk factors. To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. Questionnaire data on atopic diseases from 850 monozygotic and 2279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Cesarean section, maternal age at birth, parental cohabitation, season of birth and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR = 1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction. © 2014 John Wiley & Sons Ltd.

  19. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2013-04-01

    FTD), FTD with Parkinsonism , and early-onset Alzheimer Disease (EOAD)-like presentations. Using whole exome capture with subsequent sequencing, we...dementia. The MAPT R406W mutation is associated with EOAD-like symptoms and Parkinsonism without FTD, as well as distinct cognitive courses. KEY...OUTCOMES: Carney RM, Kohli MA, Kunkle BW, Naj AC, Gilbert JR, Züchner S, PERICAK-VANCE MA, Parkinsonism and distinct dementia patterns in a

  20. Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease.

    PubMed

    Chaudhury, Sultan; Patel, Tulsi; Barber, Imelda S; Guetta-Baranes, Tamar; Brookes, Keeley J; Chappell, Sally; Turton, James; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Hardy, John; Mann, David; Morgan, Kevin

    2018-02-01

    Sporadic early-onset Alzheimer's disease (sEOAD) exhibits the symptoms of late-onset Alzheimer's disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer's disease (AD) identifies APOEε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases was genotyped on the NeuroX array, and PRSs were generated using PRSice. The target data set consisted of 408 sEOAD cases and 436 controls. The base data set was collated by the International Genomics of Alzheimer's Project consortium, with association data from 17,008 late-onset Alzheimer's disease cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRSs were generated using all common single nucleotide polymorphisms between the base and target data set, PRS were also generated using only single nucleotide polymorphisms within a 500 kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap among the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. [Drug treatment of early-stage (de novo and "honeymoon") Parkinson disease].

    PubMed

    Cesaro, P; Defebvre, L

    2014-04-01

    In this article, we discuss the management of motor symptoms during the early phases of Parkinson's disease, excluding that of any other clinical manifestation. We relied primarily upon recently published data and do not describe older publications relating to anticholinergic drugs or amantadine. The initial pharmacological treatment of idiopathic Parkinson's disease (IPD) is symptomatic and remains based upon dopaminergic drugs. However, the development of new drugs has broadened the range of strategic options and improved overall patient management. Announcing the diagnosis is a critical moment, as pointed out by patients' associations. Patients should be advised to maintain personal, professional, social and physical activities as long as possible. The potential benefit of early pharmacological treatment should be explained, focusing on the possible disease-modifying effect of drugs such as rasagiline. According to current guidelines, L-Dopa is preferred in patients above 65years of age, while those below 65 should be treated with dopamine agonists. Like monoamine oxidase inhibitors B (MAOI-B), synthetic dopamine agonists exhibit several advantages: easy-to-use treatment with a once-daily administration, delayed L-Dopa initiation, significant efficacy on motor symptoms (although lower than that of L-Dopa). MOAI can be prescribed in association with L-Dopa or dopamine agonists. Rasagiline also delays L-Dopa initiation, and consequently motor complications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Differential roles of osteopontin/Eta-1 in early and late lpr disease

    PubMed Central

    Weber, G F; Cantor, H

    2001-01-01

    The cytokine osteopontin (Eta-1) leads to macrophage-dependent polyclonal B-cell activation and is induced early in autoimmune prone mice with the lpr mutation, suggesting a significant pathogenic role for this molecule. Indeed, C57BL/6-Faslpr/lpr mice crossed with osteopontin−/– mice display delayed onset of polyclonal B-cell activation, as judged by serum immunoglobulin levels. In contrast, they are subject to normal onset, but late exacerbation of lymphoproliferation and evidence of kidney disease. These observations define two stages of Faslpr/lpr disease with respect to osteopontin-dependent pathogenesis that should be taken into account in the design of therapeutic approaches to the clinical disease. PMID:11737079

  3. Depression is an early disease manifestation in lupus-prone MRL/lpr mice.

    PubMed

    Gao, Hua-Xin; Campbell, Sean R; Cui, Min-Hui; Zong, Pu; Hee-Hwang, Jong; Gulinello, Maria; Putterman, Chaim

    2009-02-15

    Many lupus patients develop neuropsychiatric manifestations, including cognitive dysfunction, depression, and anxiety. However, it is not clear if neuropsychiatric lupus is a primary disease manifestation, or is secondary to non-CNS disease. We found that MRL/lpr lupus-prone mice exhibited significant depression-like behavior already at 8 weeks of age, despite normal visual working memory, locomotor coordination and social preference. Moreover, depression was significantly correlated with titers of autoantibodies against DNA, NMDA receptors and cardiolipin. Our results indicate that lupus mice develop depression and CNS dysfunction very early in the course of disease, in the absence of substantial pathology involving other target organs.

  4. Symptomatic Early Congenital Syphilis: A Common but Forgotten Disease.

    PubMed

    Rashid, Usman; Yaqoob, Usman; Bibi, Nazia; Bari, Attia

    2015-10-01

    Congenital syphilis is a severe, disabling infection often with grave consequences seen in infants. It occurs due to the transmission of the disease from an infected mother to the unborn infant through the placenta. Congenital syphilis can involve any organ system and present with various symptoms. However, early diagnosis of congenital syphilis is difficult because more than half of the affected infants are asymptomatic, and the signs in symptomatic infants may be subtle and nonspecific. The continuing prevalence of this disease reveals the failure of control measures established for its prevention. Here we report a case of a one-month infant who presented with skin rash. The report stresses upon the importance of implementing the World Health Organization's recommendation that all pregnant women should be screened for syphilis in the first antenatal visit in the first trimester and again in the late pregnancy.

  5. Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

    PubMed Central

    Day, Gregory S.; Gordon, Brian A.; Jackson, Kelley; Christensen, Jon J.; Ponisio, Maria Rosana; Su, Yi; Ances, Beau M; Benzinger, Tammie L.S.; Morris, John C.

    2017-01-01

    Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype. PMID:28394771

  6. Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

    PubMed

    Day, Gregory S; Gordon, Brian A; Jackson, Kelley; Christensen, Jon J; Rosana Ponisio, Maria; Su, Yi; Ances, Beau M; Benzinger, Tammie L S; Morris, John C

    2017-01-01

    Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age. PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

  7. A critical review: early life nutrition and prenatal programming for adult disease.

    PubMed

    Carolan-Olah, Mary; Duarte-Gardea, Maria; Lechuga, Julia

    2015-12-01

    To present the evidence in relation to early life nutrition and foetal programming for adult disease. Epigenetics is a new and growing area of study investigating the impact of the intrauterine environment on the lifelong health of individuals. Discursive paper. Searches were conducted in a range of electronic health databases. Hand searches located additional articles for review. Maternal search terms included: pregnancy; nutrition; diet; obesity; over nutrition; under nutrition. Offspring related search terms included: macrosomia; intrauterine growth restriction; epigenetics; foetal programming; childhood obesity; adolescent obesity; adolescent type 2 diabetes. Results indicate that foetal programming for adult disease occurs in response to particular insults during vulnerable developmental periods. Four main areas of foetal exposure were identified in this review: (1) under nutrition; (2) over nutrition; (3) gestational diabetes mellitus; and (4) infant catch-up growth. Numerous studies also described the trans-generational nature of foetal programming. Overall, foetal exposure to excess or insufficient nutrition during vulnerable developmental periods appears to result in a lifelong predisposition to obesity and adult disease, such as type 2 diabetes and cardiac disease. For the infant who has been undernourished during early life, a predisposition to renal disease also occurs. Pregnancy is a time when women are engaged in health systems and are receptive to health messages. These factors suggest that pregnancy may be an optimal time for dietary education and intervention. There is a particular need for education on healthy diet and for interventions which aim to limit over consumption of calories. © 2015 John Wiley & Sons Ltd.

  8. Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease

    PubMed Central

    Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm

    2011-01-01

    Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877

  9. Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease.

    PubMed

    Lonie, Jane A; Herrmann, Lucie L; Tierney, Kevin M; Donaghey, Claire; O'Carroll, Ronan; Lee, Andrew; Ebmeier, Klaus P

    2009-03-01

    Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out-patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.

  10. Putaminal volume and diffusion in early familial Creutzfeldt-Jakob disease.

    PubMed

    Seror, Ilana; Lee, Hedok; Cohen, Oren S; Hoffmann, Chen; Prohovnik, Isak

    2010-01-15

    The putamen is centrally implicated in the pathophysiology of Creutzfeldt-Jakob Disease (CJD). To our knowledge, its volume has never been measured in this disease. We investigated whether gross putaminal atrophy can be detected by MRI in early stages, when the diffusion is already reduced. Twelve familial CJD patients with the E200K mutation and 22 healthy controls underwent structural and diffusion MRI scans. The putamen was identified in anatomical scans by two methods: manual tracing by a blinded investigator, and automatic parcellation by a computerized segmentation procedure (FSL FIRST). For each method, volume and mean Apparent Diffusion Coefficient (ADC) were calculated. ADC was significantly lower in CJD patients (697+/-64 microm(2)/s vs. 750+/-31 microm(2)/s, p<0.005), as expected, but the volume was not reduced. The computerized FIRST delineation yielded comparable ADC values to the manual method, but computerized volumes were smaller than manual tracing values. We conclude that significant diffusion reduction in the putamen can be detected by delineating the structure manually or with a computerized algorithm. Our findings confirm and extend previous voxel-based and observational studies. Putaminal volume was not reduced in our early-stage patients, thus confirming that diffusion abnormalities precede detectible atrophy in this structure.

  11. Early childhood diarrhoeal diseases and cognition: are we missing the rest of the iceberg?

    PubMed

    MacIntyre, Jessica; McTaggart, Jennifer; Guerrant, Richard L; Goldfarb, David M

    2014-11-01

    Risk factors which interfere with cognitive function are especially important during the first 2 years of life - a period referred to as early child development and a time during which rapid growth and essential development occur. Malnutrition, a condition whose effect on cognitive function is well known, has been shown to be part of a vicious cycle with diarrhoeal diseases, and the two pathologies together continue to be the leading cause of illness and death in young children in developing countries. This paper reviews the burden of early childhood diarrhoeal diseases globally and the emerging evidence of their relationship with global disparities in neurocognitive development. The strength of evidence which indicates that the severe childhood diarrhoeal burden may be implicated in cognitive impairment of children from low- and middle-income counties is discussed. Findings suggest that greater investment in multi-site, longitudinal enteric infection studies that assess long-term repercussions are warranted. Furthermore, economic analyses using the concept of human capital should play a key role in advancing our understanding of the breadth and complexities of the health, social and economic ramifications of early childhood diarrhoeal diseases and enteric infections. This broadened awareness can serve to help advocate for more effective interventions, particularly in developing economies.

  12. Anorectal Manometric Dysfunctions in Newly Diagnosed, Early-Stage Parkinson's Disease

    PubMed Central

    Sung, Hye Young; Kim, Yeong-In; Lee, Kwang-Soo

    2012-01-01

    Background and Purpose Anorectal dysmotility is common in advanced Parkinson's disease (PD), but there have been few evaluations in newly diagnosed PD patients. Methods We conducted anorectal manometric evaluations in 19 newly diagnosed, drug-naïve, early-stage PD patients. All of the PD patients were questioned regarding the presence of anorectal symptoms. Results Anorectal manometry was abnormal in 12 of the 19 patients. These abnormalities were more common in patients with more severe anorectal symptoms, as measured using a self-reported scale. However, more than 40% of patients with no or minimal symptoms also exhibited manometric abnormalities. Conclusions These results suggest that anorectal dysmotility manifests in many early-stage PD patients, which this represent evidence for the involvement of neuronal structures in such nonmotor manifestations in PD. PMID:23091527

  13. Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

    PubMed Central

    Janz, Philipp; Schwaderlapp, Niels; Heining, Katharina; Häussler, Ute; Korvink, Jan G; von Elverfeldt, Dominik; Hennig, Jürgen; Egert, Ulrich

    2017-01-01

    Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window. DOI: http://dx.doi.org/10.7554/eLife.25742.001 PMID:28746029

  14. Multiple begomoviruses found associated with cotton leaf curl disease in Pakistan in early 1990 are back in cultivated cotton

    USDA-ARS?s Scientific Manuscript database

    The first epidemic of cotton leaf curl disease (CLCuD) in the early 1990’s on the Indian subcontinent was associated with several distinct begomoviruses along with a disease-specific betasatellite. Resistant cotton varieties were introduced in the late 1990’s, but resistance was broken in early 2000...

  15. Phosphorus and proton magnetic resonance spectroscopy demonstrates mitochondrial dysfunction in early and advanced Parkinson's disease.

    PubMed

    Hattingen, Elke; Magerkurth, Jörg; Pilatus, Ulrich; Mozer, Anne; Seifried, Carola; Steinmetz, Helmuth; Zanella, Friedhelm; Hilker, Rüdiger

    2009-12-01

    Mitochondrial dysfunction hypothetically contributes to neuronal degeneration in patients with Parkinson's disease. While several in vitro data exist, the measurement of cerebral mitochondrial dysfunction in living patients with Parkinson's disease is challenging. Anatomical magnetic resonance imaging combined with phosphorus and proton magnetic resonance spectroscopic imaging provides information about the functional integrity of mitochondria in specific brain areas. We measured partial volume corrected concentrations of low-energy metabolites and high-energy phosphates with sufficient resolution to focus on pathology related target areas in Parkinson's disease. Combined phosphorus and proton magnetic resonance spectroscopic imaging in the mesostriatal region was performed in 16 early and 13 advanced patients with Parkinson's disease and compared to 19 age-matched controls at 3 Tesla. In the putamen and midbrain of both Parkinson's disease groups, we found a bilateral reduction of high-energy phosphates such as adenosine triphophosphate and phosphocreatine as final acceptors of energy from mitochondrial oxidative phosphorylation. In contrast, low-energy metabolites such as adenosine diphophosphate and inorganic phosphate were within normal ranges. These results provide strong in vivo evidence that mitochondrial dysfunction of mesostriatal neurons is a central and persistent phenomenon in the pathogenesis cascade of Parkinson's disease which occurs early in the course of the disease.

  16. Contribution of early Alzheimer's Disease-related Pathophysiology to the Development of Acquired epilepsy.

    PubMed

    Gschwind, Tilo; Lafourcade, Carlos; Gfeller, Tim; Zaichuk, Mariana; Rambousek, Lukas; Knuesel, Irene; Fritschy, Jean-Marc

    2018-06-04

    Aberrant epileptic activity is detectable at early disease stages in Alzheimer's disease (AD) patients and in AD mouse models. Here, we investigated in young ArcticAβ mice whether AD-like pathology renders neuronal networks more susceptible to development of acquired epilepsy induced by unilateral intrahippocampal injection of kainic acid (IHK). In this temporal lobe epilepsy model, IHK induces a status epilepticus followed after two weeks by spontaneous recurrent seizures (SRS). ArcticAβ mice exhibited more severe status epilepticus and early onset of SRS. This hyperexcitable phenotype was characterized in CA1 neurons by decreased synaptic strength, increased kainic acid-induced LTP, and reduced frequency of spontaneous inhibitory currents. However, no difference in neurodegeneration, neuroinflammation, axonal reorganization or adult neurogenesis was observed in ArcticAβ mice compared to wildtype littermates following IHK-induced epileptogenesis. Neuropeptide Y (NPY) expression was reduced at baseline and its IHK-induced elevation in mossy fibers and granule cells was attenuated. However, although this alteration might underlie premature seizure onset, neutralization of soluble Aβ species by intracerebroventricular Aβ-specific antibody application mitigated the hyperexcitable phenotype of ArcticAβ mice and prevented early SRS onset. Therefore, development of seizures at early stages of AD is mediated primarily by Aβ species causing widespread changes in synaptic function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.

    PubMed

    Lakatos, Laszlo; Kiss, Lajos S; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Lakatos, Peter Laszlo

    2011-12-01

    Recent trends indicate a change in the epidemiology of inflammatory bowel diseases (IBD), with previously low incidence areas now reporting a progressive rise in the incidence. Our aim was to analyze the incidence and disease phenotype at diagnosis in IBD in the population-based Veszprem Province database, which included incident patients diagnosed between January 1, 2002 and December 31, 2006. Data of 393 incident patients were analyzed (ulcerative colitis [UC]: 220, age-at-diagnosis: 40.5 years; Crohn's disease [CD]: 163, age-at-diagnosis: 32.5 years; and indeterminate colitis [IC]: 10). Both hospital and outpatient records were collected and comprehensively reviewed. Adjusted mean incidence rates were 8.9/10(5) person-years for CD and 11.9/10(5) person-years in UC. Peak onset age in both CD and UC patients was 21-30 years old. Location at diagnosis in UC was proctitis in 26.8%, left-sided colitis in 50.9%, and pancolitis in 22.3%. The probability of proximal extension and colectomy after 5 years was 12.7% and 2.8%. The disease location in CD was ileal in 20.2%, colonic in 35.6%, ileocolonic in 44.2%, and upper gastrointestinal in four patients. Behavior at diagnosis was stenosing/penetrating in 35.6% and perianal in 11.1%. Patients with colonic disease were older at diagnosis compared to patients with ileal or ileocolonic disease. In a Kaplan-Meier analysis, probability of surgical resection was 9.8%, 18.5%, and 21.3% after 1, 3, and 5 years of disease duration, respectively. The incidence of IBD in Veszprem Province in the last decade was high, equal to that in high-incidence areas in Western European countries. Early disease course is milder compared to data reported in the literature. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  18. Early Renal Involvement in a Girl with Classic Fabry Disease.

    PubMed

    Perretta, Fernando; Antongiovanni, Norberto; Jaurretche, Sebastián

    2017-01-01

    Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the enzyme alpha galactosidase A; this defect leads to the systemic accumulation of globotriaosylceramide and its metabolites. Organic involvement in men is well known, but in women it is controversial, mainly due to the random X-chromosome inactivation in each of their cells (Lyon hypothesis). This would explain why women (heterozygotes) present a wide variability in the severity of their phenotype. The manifestations are multisystemic and begin in early childhood, reaching a severe compromise in adulthood. Typical acroparesthesia in hands and feet, gastrointestinal symptoms, angiokeratomas, dyshidrosis, hearing loss, arrhythmias, hypertrophic cardiomyopathy, cerebrovascular accidents, and renal failure can be observed. Nephropathy is one of the major complications of Fabry disease. Glomerular and vascular changes are present before progression to overt proteinuria and decreased glomerular filtration rate, even in pediatric patients. A case of incipient renal involvement in a girl with classic Fabry disease is reported.

  19. Predictors of weight loss in early treated Parkinson's disease from the NET-PD LS-1 cohort.

    PubMed

    Wills, Anne-Marie; Li, Ruosha; Pérez, Adriana; Ren, Xuehan; Boyd, James

    2017-08-01

    Weight loss is a common symptom of Parkinson's disease and is associated with impaired quality of life. Predictors of weight loss have not been studied in large clinical cohorts. We previously observed an association between change in body mass index and change in Unified Parkinson's Disease Rating Scale (UPDRS) motor and total scores. In this study, we performed a secondary analysis of longitudinal data (1-6 years) from 1619 participants in the NINDS Exploratory Trials in PD Long-term Study-1 (NET-PD LS1) to explore predictors of weight loss in a large prospective clinical trial cohort of early treated Parkinson's disease. The NET-PD LS1 study was a double-blind randomized placebo controlled clinical trial of creatine monohydrate 10 gm/day in early treated PD (within 5 years of diagnosis and within 2 years of starting dopaminergic medications). Linear mixed models were used to estimate the effect of baseline clinical covariates on weight change over time. On average, participants lost only 0.6 kg per year. Higher age, baseline weight, female gender, higher baseline UPDRS scores, greater postural instability, difficulty eating and drinking, lower cognitive scores and baseline levodopa use (compared to dopamine agonists) were all associated with weight loss. Surprisingly baseline difficulty swallowing, dyskinesia, depression, intestinal hypomotility (constipation) and self-reported nausea/vomiting/anorexia were not significantly associated with weight loss in this cohort of early treated Parkinson's disease patients. On average, participants with Parkinson's disease experience little weight loss during the first 1-6 years after starting dopaminergic replacement therapy, however levodopa use and postural instability were both predictors of early weight loss. Trial Registration clinicaltrials.gov identifier# NCT00449865.

  20. The reorganization of functional architecture in the early-stages of Parkinson's disease.

    PubMed

    Tuovinen, Noora; Seppi, Klaus; de Pasquale, Francesco; Müller, Christoph; Nocker, Michael; Schocke, Michael; Gizewski, Elke R; Kremser, Christian; Wenning, Gregor K; Poewe, Werner; Djamshidian, Atbin; Scherfler, Christoph; Seki, Morinobu

    2018-05-01

    The study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. 3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ± 1.2 years at baseline with a clinical follow-up of 1.5 ± 0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. At baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. Resting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. High-accuracy detection of early Parkinson's Disease using multiple characteristics of finger movement while typing

    PubMed Central

    2017-01-01

    Parkinson’s Disease (PD) is a progressive neurodegenerative movement disease affecting over 6 million people worldwide. Loss of dopamine-producing neurons results in a range of both motor and non-motor symptoms, however there is currently no definitive test for PD by non-specialist clinicians, especially in the early disease stages where the symptoms may be subtle and poorly characterised. This results in a high misdiagnosis rate (up to 25% by non-specialists) and people can have the disease for many years before diagnosis. There is a need for a more accurate, objective means of early detection, ideally one which can be used by individuals in their home setting. In this investigation, keystroke timing information from 103 subjects (comprising 32 with mild PD severity and the remainder non-PD controls) was captured as they typed on a computer keyboard over an extended period and showed that PD affects various characteristics of hand and finger movement and that these can be detected. A novel methodology was used to classify the subjects’ disease status, by utilising a combination of many keystroke features which were analysed by an ensemble of machine learning classification models. When applied to two separate participant groups, this approach was able to successfully discriminate between early-PD subjects and controls with 96% sensitivity, 97% specificity and an AUC of 0.98. The technique does not require any specialised equipment or medical supervision, and does not rely on the experience and skill of the practitioner. Regarding more general application, it currently does not incorporate a second cardinal disease symptom, so may not differentiate PD from similar movement-related disorders. PMID:29190695

  2. Long-term Assessment of Post-Treatment Symptoms in Patients With Culture-Confirmed Early Lyme Disease.

    PubMed

    Weitzner, Erica; McKenna, Donna; Nowakowski, John; Scavarda, Carol; Dornbush, Rhea; Bittker, Susan; Cooper, Denise; Nadelman, Robert B; Visintainer, Paul; Schwartz, Ira; Wormser, Gary P

    2015-12-15

    Lyme disease patients with erythema migrans are said to have post-treatment Lyme disease symptoms (PTLDS) if there is persistence of subjective symptoms for at least 6 months following antibiotic treatment and resolution of the skin lesion. The purpose of this study was to characterize PTLDS in patients with culture-confirmed early Lyme disease followed for >10 years. Adult patients with erythema migrans with a positive skin or blood culture for Borrelia burgdorferi were enrolled in a prospective study beginning in 1991 and followed up at 6 months and annually thereafter to determine the long-term outcome of this infection. The genotype of the infecting strain of B. burgdorferi was evaluated in subjects with PTLDS. One hundred twenty-eight subjects with culture-confirmed early Lyme disease, of whom 55% were male, were followed for a mean ± SD of 14.98 ± 2.71 years (median = 15 years; range = 11-20 years). Fourteen (10.9%) were regarded as having possible PTLDS, but only 6 (4.7%) had PTLDS documented at their last study visit. Nine (64.3%) had only a single symptom. None of the 6 with PTLDS at their last visit was considered to be functionally impaired by the symptom(s). PTLDS was not associated with a particular genotype of B. burgdorferi. PTLDS may persist for >10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Early pathology in sleep studies of patients with familial Creutzfeldt-Jakob disease.

    PubMed

    Givaty, Gili; Maggio, Nicola; Cohen, Oren S; Blatt, Ilan; Chapman, Joab

    2016-10-01

    In this study, we aimed to assess sleep function in patients with recent-onset familial Creutzfeldt-Jakob disease (fCJD). The largest cluster of fCJD patients is found in Jews of Libyan origin, linked to the prion protein gene (PRNP) E200K mutation. The high index of suspicion in these patients often leads to early diagnosis, with complaints of insomnia being a very common presenting symptom of the disease. The study included 10 fCJD patients diagnosed by clinical manifestations, magnetic resonance imaging (MRI) scan of the brain, elevated tau protein in the cerebrospinal fluid (CSF) and positive PRNP E200K mutation. Standard polysomnography was performed after a brief interview confirming the presence of sleep disturbances. All patients showed a pathological sleep pattern according to all scoring evaluation settings. The sleep stages were characterized by (i) disappearance of sleep spindles; (ii) outbursts of periodic sharp waves and shallowing of sleep consisting in increased Stage 2 and wake periods during the night, as well as decrease of slow-wave sleep and rapid eye movement (REM) sleep. Recordings of respiratory functions reported irregular breathing with central and obstructive apnea and hypopnea. The typical hypotonia occurring during the night and atonia during REM sleep were replaced by hyperactive sleep consisting of multiple jerks, movements and parasomnia (mainly talking) throughout the night. In conclusion, we report unique pathological sleep patterns in early fCJD associated with the E200K mutation. Specific respiratory disturbances and lack of atonia could possibly serve as new, early diagnostic tools in the disease. © 2016 European Sleep Research Society.

  4. Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.

    PubMed

    Kawai, Toshinao; Arai, Katsuhiro; Harayama, Shizuko; Nakazawa, Yumiko; Goto, Fumihiro; Maekawa, Takanobu; Tamura, Eiichiro; Uchiyama, Toru; Onodera, Masafumi

    2015-08-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that leads to recurrent infection and hyper-inflammation, occasionally represented by CGD-associated colitis (CGD colitis). Although clinical symptoms of CGD colitis mimic those of ulcerative colitis (UC), there is no reliable standard measurement of disease activity or standard therapeutic strategy for CGD colitis. Here, we examined the clinical manifestation of CGD colitis based on severity using a noninvasive measure of disease activity, the Pediatric Ulcerative Colitis Activity Index (PUCAI), which has been validated and widely used for pediatric UC. Sixteen of 35 CGD patients, who were diagnosed with CGD colitis based on colonoscopic and histological findings, were examined using the PUCAI. Both the PUCAI and the physician global assessment (PGA) tool were retrospectively scored by reviewing medical records. Disease activity defined by PUCAI was correlated with PGA, and increased at diagnosis of CGD colitis, especially in patients who were younger than 6 years of age (very early-onset CGD colitis: VEO-CGD colitis) when diagnosed with CGD colitis. All severe patients had a more progressive form of VEO-CGD colitis. Unlike mild and moderate patients, severe patients required multidrug therapy of corticosteroids and immunomodulator/immunosuppressants, and some were eventually treated with hematopoietic stem cell transplantation. Although the validation of PUCAI in CGD colitis should be considered for future use, our results indicate that noninvasive measures could be effective to measure disease activity and help to determine suitable treatment for CGD colitis. In patients with VEO-CGD colitis, multidrug therapy would need to be considered at an early stage on the basis of disease activity.

  5. Alternatives to the Fish Early Life-Stage Test: A Research Strategy for Discovering and Annotating Adverse Outcome Pathways During Fish Development

    EPA Science Inventory

    The OECD 210 fish early life]stage (FELS) test is the primary guideline test used to estimate chronic fish toxicity, as well as support ecological risk assessments and chemical management programs around the world. As a step toward developing alternatives to the FELS test, a HES...

  6. Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

    PubMed

    Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

    2018-02-01

    Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

  7. Signal and image processing for early detection of coronary artery diseases: A review

    NASA Astrophysics Data System (ADS)

    Mobssite, Youness; Samir, B. Belhaouari; Mohamad Hani, Ahmed Fadzil B.

    2012-09-01

    Today biomedical signals and image based detection are a basic step to diagnose heart diseases, in particular, coronary artery diseases. The goal of this work is to provide non-invasive early detection of Coronary Artery Diseases relying on analyzing images and ECG signals as a combined approach to extract features, further classify and quantify the severity of DCAD by using B-splines method. In an aim of creating a prototype of screening biomedical imaging for coronary arteries to help cardiologists to decide the kind of treatment needed to reduce or control the risk of heart attack.

  8. Disease Management of Early Childhood Caries: ECC Collaborative Project.

    PubMed

    Ng, Man Wai; Ramos-Gomez, Francisco; Lieberman, Martin; Lee, Jessica Y; Scoville, Richard; Hannon, Cindy; Maramaldi, Peter

    2014-01-01

    Until recently, the standard of care for early childhood caries (ECC) has been primarily surgical and restorative treatment with little emphasis on preventing and managing the disease itself. It is now recognized that surgical treatment alone does not address the underlying etiology of the disease. Despite costly surgeries and reparative treatment, the onset and progression of caries are likely to continue. A successful rebalance of risk and protective factors may prevent, slow down, or even arrest dental caries and its progression. An 18-month risk-based chronic disease management (DM) approach to address ECC in preschool children was implemented as a quality improvement (QI) collaborative by seven teams of oral health care providers across the United States. In the aggregate, fewer DM children experienced new cavitation, pain, and referrals to the operating room (OR) for restorative treatment compared to baseline historical controls. The teams found that QI methods facilitated adoption of the DM approach and resulted in improved care to patients and better outcomes overall. Despite these successes, the wide scale adoption and spread of the DM approach may be limited unless health policy and payment reforms are enacted to compensate providers for implementing DM protocols in their practice.

  9. Effects of fine sediment, hyporheic flow, and spawning site characteristics on survival and development of bull trout embryos

    USGS Publications Warehouse

    Bowerman, Tracy; Neilson, Bethany; Budy, Phaedra

    2014-01-01

    Successful spawning is imperative for the persistence of salmonid populations, but relatively little research has been conducted to evaluate factors affecting early life-stage survival for bull trout (Salvelinus confluentus), a threatened char. We conducted a field experiment to assess the relationship between site-specific environmental factors and bull trout embryo survival and fry emergence timing. Survival from egg to hatch was negatively related to percent fine sediment (<1 mm) in the redd and positively related to the strength of downwelling at spawning sites. Survival of eggs to fry emergence was also negatively related to fine sediment, and the best statistical models included additional variables that described the rate of downwelling and intragravel flow within the incubation environment. Fry emerged at an earlier stage in development from redds with high percentages of fine sediment. Increased hydraulic conductivity via redd construction and selection of spawning sites with strong downwelling appear to enhance hyporheic flow rates and bull trout egg survival, but early life-stage success may ultimately be limited by intrusion of fine sediment into the incubation environment.

  10. Coronary artery disease: new insights into the pathophysiology, prevalence and early detection of a monster menace.

    PubMed

    Slater, James; Rill, Velisar

    2003-04-01

    Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the United States and industrialized countries. In the undeveloped world a similar epidemic is brewing. A new pathophysiologic paradigm has emerged, which assigns the mediators of inflammation a much larger role in the disease process. This paradigm has helped explain the unpredictable nature of many adverse consequences of CAD. The long latent phase of the disease and often sudden initial presentation make efforts at early detection extremely important. Considerable work has been devoted to identify as well as influence predisposing risk factors for developing arteriosclerosis. Novel markers of inflammation, like C-reactive protein, have been identified and compared to traditional risk factors. In addition, new imaging modalities introduce the possibility of screening for sub-clinical disease. Electron-beam and spiral CT scanners, as well as other techniques, are emerging as powerful tools to detect early disease presence and allow intervention to take place before major clinical events occur. Advances in our understanding of the pathophysiology and our ability to image the stages of silent disease will go hand in hand to revolutionize our approach to prevention and treatment of this deadly disease.

  11. Air pollution in early life and adult mortality from chronic rheumatic heart disease.

    PubMed

    Phillips, David I W; Osmond, Clive; Williams, Martin L; Jones, Alexander

    2017-08-01

    Chronic rheumatic heart disease (RHD) remains a globally important cause of heart disease. The reasons for the continuing high prevalence of this disease are obscure, but it may have its origins in the poor social and economic conditions with which the disease has been consistently and strongly linked. Mortality studies from the UK have suggested the importance of adverse environmental factors in early life; these studies demonstrated specific geographical associations between high rates of chest infection during infancy and subsequent RHD. They raised the possibility that early air pollution, which is known to be strongly linked with chest infection during infancy, may predispose to RHD. We related estimates of air pollution and social conditions developed by Daly in 1951-52 for 78 urban areas in England and Wales to their subsequent RHD mortality rates at ages 35-74 in men and women during 1993-2012. There were strong relationships between domestic air pollution and RHD [relative risk per standard deviation (SD) increase in pollution 1.168, 95% confidence interval (CI): 1.128 to 1.210, P < 0.001). Inclusion of published data on social class, education, crowding and population density in multiple regression analyses showed that the air pollution association was independent of these; only overcrowding was separately linked with RHD. We present the first evidence of an association between air pollution in early life and RHD. Although there are several limitations to this study, the strength and consistency of the results, together with their biological plausibility, suggest a causal link. This deserves attention because it may have important consequences for the control of RHD in resource-poor countries where widespread use of biomass fuels and domestic pollution remain a problem. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  12. [Implementation of an early rheumatoid athritis unit for the early recognition and treatment of the disease].

    PubMed

    Espinoza, Francisco; Monckeberg, Gustavo; Hassi, Isabel; Queirolo, Alejandra; Chicao, Fernando; Sandoval, Ximena; Jorquera, Evelyn; Badilla, Alejandro

    2018-01-01

    Early recognition of rheumatoid arthritis (RA) provides clinical benefits in terms of remission induction, reduced disease progression, and eventually treatment free remission. To describe the setting of a Unit devoted exclusively to the recognition and treatment of early RA in patients referred from primary healthcare centers (PHC) in Chile. Patients were referred from nine participating PHC from 2014 through 2016. PHC physicians received a formal training to enhance criteria recognition and program adherence. Mandatory referral criteria were an age above 17 years, and arthralgia of less than 1-year duration, plus at least one of the following: morning stiffness of more than 30 minutes, swelling involving more than 3 joints for more than 1 month, a positive squeeze test or abnormal inflammatory serum markers. One hundred twenty patients aged 45 ± 12 years (90% women) were assessed at the early rheumatoid arthritis unit. Median time to referral from PHC to the Unit was 14.6 days. The median duration of symptoms for the overall sample of patients was 10.8 months. RA was identified in 43 patients (36%), with a delay between onset of symptoms and diagnosis of 8.3 months. Regarding the performance of referral criteria, the most sensitive was morning stiffness (80%, sensitivity 95% confidence intervals (CI) 64-89%) and synovitis was the most specific (specificity 83%, 95% CI 72-90%). The positive predictive value of the three clinical criteria altogether was 68.1% (95% CI 47-83%). Institution of an early RA unit was feasible within the Chilean healthcare system enabling the identification of early RA in one-third of patients.

  13. Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

    PubMed Central

    Bailey, Kathryn A.; Smith, Allan H.; Tokar, Erik J.; Graziano, Joseph H.; Kim, Kyoung-Woong; Navasumrit, Panida; Ruchirawat, Mathuros; Thiantanawat, Apinya; Suk, William A.; Fry, Rebecca C.

    2015-01-01

    Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360 PMID:26115410

  14. [Early detection of occupational skin diseases in sewer workers].

    PubMed

    Lang, V; Lauffer, F; Fincan, Y; Biedermann, T; Zink, A

    2018-04-25

    Skin diseases affect 30-70% of the world population, and globally, skin cancer rates are continuously increasing. In this respect, prevention programs and early detection of skin diseases are of particular importance. To screen sewer workers for skin diseases with regard to their work-related risk. Employees of the municipal utilities in Munich (Münchner Stadtentwässerung) underwent a whole-body examination of the skin, conducted by two dermatologists. In addition, all employees completed a paper-based questionnaire on risk behavior and preventive measures. We examined 81 employees (79 men, 2 women, mean age 45.7 ± 9.5 years). Skin lesions in need of treatment were found in 30.9% (n = 25): the most frequent diagnosis was mycosis pedis (16.1%). In addition, one employee was diagnosed with basal cell carcinoma and two with actinic keratoses. According to the questionnaire, 43.5% of the employees had undergone a physician-led skin cancer screening in the past, whereas sun-protection practices were rarely applied. According to our findings, employee skin cancer screening seems to be beneficial for the detection of work-related skin diseases and is associated with a high participation rate. Furthermore, the study suggests that sewer workers have a high rate of mycosis pedis, possibly a work-related effect.

  15. [Neuroprotective subthalamotomy in Parkinson's disease. The role of magnetic resonance-guided focused ultrasound in early surgery].

    PubMed

    Guridi, Jorge; Marigil, Miguel; Becerra, Victoria; Parras, Olga

    Subthalamic nucleus hyperactivity in Parkinson's disease may be a very early phenomenon. Its start is not well known, and it may occur during the pre-symptomatic disease stage. Glutamatergic hyperactivity may be neurotoxic over the substantia nigra compacta dopaminergic neurons. If this occurred, the excitatory neurotransmitter, glutamate, should affect the neurons that maintain a high turnover as a compensatory mechanism. Would a subthalamic nucleus lesion decrease this hyperactivity and thus be considered as a neuroprotective mechanism for dopaminergic neurons? The authors hypothesise about the possibility to perform surgery on a subthalamic nucleus lesion at a very early stage in order to avoid the neurotoxic glutamatergic effect over the dopaminergic neurons, and therefore be considered as a neuroprotective surgery able to alter the progress of the disease during early motor symptoms. In this regard, magnetic resonance-guided focused ultrasound techniques open a new window in the stereotactic armamentarium. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study.

    PubMed

    Lin, Feng-Cheng; Chuang, Yun-Shiuan; Hsieh, Hui-Min; Lee, Tzu-Chi; Chiu, Kuei-Fen; Liu, Ching-Kuan; Wu, Ming-Tsang

    2015-11-01

    The protective effect of statin on Alzheimer disease (AD) is still controversial, probably due to the debate about when to start the use of statin and the lack of any large-scale randomized evidence that actually supports the hypothesis. The purpose of this study was to examine the protective effect of early statin use on mild-to-moderate AD in the total Taiwanese population.This was a total population-based case-control study, using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The study patients were those with newly diagnosed dementia (ICD-9 290.x) and prescribed any acetylcholinesterase inhibitors (AChEI) from the Taiwan National Health Insurance dataset in 1997 to 2008. The newly diagnosed eligible mild-to-moderate AD patients were traced from the dates of their index dates, which was defined as the first day to receive any AChEI treatment, back to 1 year (exposure period) to categorize them into AD with early statin use and without early statin use. Early statin use was defined as patients using statin before AChEI treatment. Alzheimer disease patients with early statin use were those receiving any statin treatment during the exposure period. Then, we used propensity-score-matched strategy to match these 2 groups as 1:1. The matched study patients were followed-up from their index dates. The primary outcome was the discontinuation of AChEI treatment, indicating AD progression.There were 719 mild-to-moderate AD-paired patients with early statin use and without early statin use for analyses. Alzheimer disease progression was statistically lower in AD patients with early statin use than those without (P = 0.00054). After adjusting for other covariates, mild-to-moderate AD patients with early stain use exhibited a 0.85-risk (95% CI = 0.76-0.95, P = 0.0066) to have AD progression than those without.Early statin use was significantly associated with a reduction in AD

  17. Alzheimer's Disease Early Diagnosis Using Manifold-Based Semi-Supervised Learning.

    PubMed

    Khajehnejad, Moein; Saatlou, Forough Habibollahi; Mohammadzade, Hoda

    2017-08-20

    Alzheimer's disease (AD) is currently ranked as the sixth leading cause of death in the United States and recent estimates indicate that the disorder may rank third, just behind heart disease and cancer, as a cause of death for older people. Clearly, predicting this disease in the early stages and preventing it from progressing is of great importance. The diagnosis of Alzheimer's disease (AD) requires a variety of medical tests, which leads to huge amounts of multivariate heterogeneous data. It can be difficult and exhausting to manually compare, visualize, and analyze this data due to the heterogeneous nature of medical tests; therefore, an efficient approach for accurate prediction of the condition of the brain through the classification of magnetic resonance imaging (MRI) images is greatly beneficial and yet very challenging. In this paper, a novel approach is proposed for the diagnosis of very early stages of AD through an efficient classification of brain MRI images, which uses label propagation in a manifold-based semi-supervised learning framework. We first apply voxel morphometry analysis to extract some of the most critical AD-related features of brain images from the original MRI volumes and also gray matter (GM) segmentation volumes. The features must capture the most discriminative properties that vary between a healthy and Alzheimer-affected brain. Next, we perform a principal component analysis (PCA)-based dimension reduction on the extracted features for faster yet sufficiently accurate analysis. To make the best use of the captured features, we present a hybrid manifold learning framework which embeds the feature vectors in a subspace. Next, using a small set of labeled training data, we apply a label propagation method in the created manifold space to predict the labels of the remaining images and classify them in the two groups of mild Alzheimer's and normal condition (MCI/NC). The accuracy of the classification using the proposed method is 93

  18. Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life.

    PubMed

    Nakamoto, Tetsuo; Rawls, H Ralph

    2018-05-15

    Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.

  19. Early Detection of Chronic Obstructive Pulmonary Disease in Primary Care.

    PubMed

    Kobayashi, Seiichi; Hanagama, Masakazu; Yanai, Masaru

    2017-12-01

    Objective To evaluate the effectiveness of an early detection program for chronic obstructive pulmonary disease (COPD) in a primary care setting in Japan. Methods Participants of ≥40 years of age who regularly visited a general practitioner's clinic due to chronic disease were asked to complete a COPD screening questionnaire (COPD Population Screener; COPD-PS) and undergo simplified spirometry using a handheld spirometric device. Patients who showed possible COPD were referred to a respiratory specialist and underwent a detailed examination that included spirometry and chest radiography. Results A total of 111 patients with possible COPD were referred for close examination. Among these patients, 27 patients were newly diagnosed with COPD. The patients with COPD were older, had lower BMI values, and had a longer smoking history in comparison to non-COPD patients. COPD patients also had more comorbid conditions. A diagnosis of COPD was significantly associated with a high COPD-PS score (p<0.001) and the detection of possible airflow limitation evaluated by the handheld spirometric device (p<0.01). An ROC curve analysis demonstrated that 5 points was the best COPD-PS cut-off value for the diagnosis of COPD. The combination of both tools showed 40.7% of sensitivity and 96.4% of specificity. Conclusion The use of the COPD-PS plus a handheld spirometric device could facilitate the early detection of undiagnosed COPD in primary care.

  20. Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson's disease.

    PubMed

    Marconi, S; Zwingers, T

    2014-07-01

    The monoamine oxidase B inhibitors selegiline and rasagiline have not been compared in head-to-head clinical trials in patients with early Parkinson's disease.  The aim of this review was to compare the efficacy of these two agents in this setting. Randomized, placebo-controlled trials with an endpoint of the mean change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) total score were included. Analysis included calculation of the standardized mean differences (SMDs) with 95% confidence intervals (CIs) and Forest Plot analyses for comparisons of pooled results. Five studies with selegiline (n = 1029) and four with rasagiline (n = 820) were included. Treatment duration was 2.5-9 months. Both selegiline and rasagiline showed significant SMDs versus placebo (-0.690, 95% CI -0.811, -0.569 and -1.025, 95% CI -1.230, -0.820; respectively), indicating a significant effect of both drugs on UPDRS. The SMD between selegiline and rasagiline was not significantly different (SMD 0.079; 95% CI -0.010, +0.167). It appears that selegiline and rasagiline have comparable efficacy in improving Parkinsonian symptoms in patients with early stage disease.

  1. Expression stability and selection of optimal reference genes for gene expression normalization in early life stage rainbow trout exposed to cadmium and copper.

    PubMed

    Shekh, Kamran; Tang, Song; Niyogi, Som; Hecker, Markus

    2017-09-01

    Gene expression analysis represents a powerful approach to characterize the specific mechanisms by which contaminants interact with organisms. One of the key considerations when conducting gene expression analyses using quantitative real-time reverse transcription-polymerase chain reaction (qPCR) is the selection of appropriate reference genes, which is often overlooked. Specifically, to reach meaningful conclusions when using relative quantification approaches, expression levels of reference genes must be highly stable and cannot vary as a function of experimental conditions. However, to date, information on the stability of commonly used reference genes across developmental stages, tissues and after exposure to contaminants such as metals is lacking for many vertebrate species including teleost fish. Therefore, in this study, we assessed the stability of expression of 8 reference gene candidates in the gills and skin of three different early life-stages of rainbow trout after acute exposure (24h) to two metals, cadmium (Cd) and copper (Cu) using qPCR. Candidate housekeeping genes were: beta actin (b-actin), DNA directed RNA polymerase II subunit I (DRP2), elongation factor-1 alpha (EF1a), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), glucose-6-phosphate dehydrogenase (G6PD), hypoxanthine phosphoribosyltransferase (HPRT), ribosomal protein L8 (RPL8), and 18S ribosomal RNA (18S). Four algorithms, geNorm, NormFinder, BestKeeper, and the comparative ΔCt method were employed to systematically evaluate the expression stability of these candidate genes under control and exposed conditions as well as across three different life-stages. Finally, stability of genes was ranked by taking geometric means of the ranks established by the different methods. Stability of reference genes was ranked in the following order (from lower to higher stability): HPRT

  2. Seizures and epileptiform activity in the early stages of Alzheimer disease.

    PubMed

    Vossel, Keith A; Beagle, Alexander J; Rabinovici, Gil D; Shu, Huidy; Lee, Suzee E; Naasan, Georges; Hegde, Manu; Cornes, Susannah B; Henry, Maya L; Nelson, Alexandra B; Seeley, William W; Geschwind, Michael D; Gorno-Tempini, Maria L; Shih, Tina; Kirsch, Heidi E; Garcia, Paul A; Miller, Bruce L; Mucke, Lennart

    2013-09-01

    Epileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease. To describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity. Retrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco. We studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7). Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications. Patients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P < .001), clustering near the onset of cognitive decline. Epilepsies were most often complex partial seizures (47%) and more than half were nonconvulsive (55%). Serial or extended EEG monitoring appeared to be more effective than routine EEG at detecting interictal and subclinical epileptiform activity. Epileptic foci were predominantly unilateral and temporal. Of the

  3. Trends of vaccine-preventable diseases in Afghanistan from the Disease Early Warning System, 2009–2015

    PubMed Central

    Mubarak, Mohammad Y.; Johnson, Laura E.; Porth, Julia M.; Yousif, Jenna E.; Boulton, Matthew L.

    2017-01-01

    Background Afghanistan’s public health system was neglected during decades of military and civil conflict, and trends in infectious disease occurrence remain poorly characterized. This study examines cyclical and long-term trends of six vaccine-preventable diseases: pneumonia, diarrhea, meningitis, typhoid, measles, and acute viral hepatitis. Methods Using weekly data collected between 2009 and 2015 through Afghanistan’s Disease Early Warning System, we calculated monthly case counts, and fit a Poisson regression with a Fourier transformation for seasonal cycles and dummy variables for year. Results We found the greatest incidence of diarrhea and typhoid in the summer, pneumonia in the winter, and measles in the late spring. Meningitis and acute viral hepatitis did not demonstrate substantial seasonality. Rates of pneumonia and diarrhea were constant across years whereas rates of meningitis, typhoid, and acute viral hepatitis decreased. Measles incidence increased in 2015. Conclusions Communicable disease reporting systems can guide public health operations–such as the implementation of new vaccines, and permit evaluation of health interventions. For example, measles supplementary immunization activities in Afghanistan have not slowed long-term transmission of the disease, but decreases in typhoid fever and acute viral hepatitis are probably tied to improvements in sanitation in the country. PMID:28570694

  4. Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease.

    PubMed

    Králík, L; Flachsová, E; Hansíková, H; Saudek, V; Zeman, J; Martásek, P

    2017-01-01

    Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C>T (p.Gln724Ter); c.3745G>T (p.Glu1249Ter); and c.3862C>T (p.Gln1288Ter). The mutation c.3745G>T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

  5. Nystagmus as an early ocular alteration in Machado-Joseph disease (MJD/SCA3)

    PubMed Central

    2014-01-01

    Background Machado-Joseph disease (MJD), also named spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia worldwide. Although nystagmus is one of the most frequently reported ocular alterations in MJD patients its behaviour during the course of the disease, namely in its early stages, has only recently started to be investigated. The main goal of this work was to characterize the frequency of nystagmus in symptomatic and presymptomatic carriers of the MJD mutation, and investigate its usefulness as an early indicator of the disease. Methods We conducted an observational study of Azorean MJD family members, comprising a total of 158 subjects which underwent neurological evaluation. Sixty eight were clinically and molecularly diagnosed with MJD, 48 were confirmed asymptomatic carriers and 42 were confirmed non-carriers of the MJD mutation. The frequency of nystagmus was calculated for the 3 groups. Results Nystagmus was present in 88% of the MJD patients. Seventeen percent of the at-risk subjects with a carrier result in the molecular test and none of the 42 individuals who received a non-carrier test result displayed nystagmus (p < 0.006). Although not reaching statistical significance, symptomatic subjects showing nystagmus had a tendency for a higher length of the CAG tract in the expanded allele, when compared to individuals who did not have nystagmus. Conclusions The frequency of nystagmus in asymptomatic carriers and its absence in non-carriers of the mutation, suggests that nystagmus may appear before gait disturbance and can thus be considered an early sign of MJD. PMID:24450306

  6. Daily Physical Activity Patterns During the Early Stage of Alzheimer's Disease.

    PubMed

    Varma, Vijay R; Watts, Amber

    2017-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when components of physical function and mobility may be preserved. Our study explored differences in daily physical activity profiles, independent of the effects of non-cognitive factors including physical function and age, among individuals with mild AD compared to controls. Patients with mild AD and controls (n = 92) recruited from the University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility. We found that mild AD was associated with less moderate-intensity physical activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity complexity (p < 0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates. These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function.

  7. The septal bulge--an early echocardiographic sign in hypertensive heart disease.

    PubMed

    Gaudron, Philipp Daniel; Liu, Dan; Scholz, Friederike; Hu, Kai; Florescu, Christiane; Herrmann, Sebastian; Bijnens, Bart; Ertl, Georg; Störk, Stefan; Weidemann, Frank

    2016-01-01

    Patients in the early stage of hypertensive heart disease tend to have normal echocardiographic findings. The aim of this study was to investigate whether pathology-specific echocardiographic morphologic and functional parameters can help to detect subclinical hypertensive heart disease. One hundred ten consecutive patients without a history and medication for arterial hypertension (AH) or other cardiac diseases were enrolled. Standard echocardiography and two-dimensional speckle-tracking-imaging analysis were performed. Resting blood pressure (BP) measurement, cycle ergometer test (CET), and 24-hour ambulatory BP monitoring (ABPM) were conducted. Patients were referred to "septal bulge (SB)" group (basal-septal wall thickness ≥ 2 mm thicker than mid-septal wall thickness) or "no-SB" group. Echocardiographic SB was found in 48 (43.6%) of 110 patients. In this SB group, 38 (79.2%) patients showed AH either by CET or ABPM. In contrast, in the no-SB group (n = 62), 59 (95.2%) patients had no positive test for AH by CET or ABPM. When AH was solely defined by resting BP, SB was a reasonable predictive sign for AH (sensitivity 73%, specificity 76%). However, when AH was confirmed by CET or ABPM the echocardiographic SB strongly predicted clinical AH (sensitivity 93%, specificity 86%). In addition, regional myocardial deformation of the basal-septum in SB group was significantly lower than in no-SB group (14 ± 4% vs. 17 ± 4%; P < .001). In conclusion, SB is a morphologic echocardiographic sign for early hypertensive heart disease. Sophisticated BP evaluation including resting BP, ABPM, and CET should be performed in all patients with an accidental finding of a SB in echocardiography. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  9. Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

    PubMed

    Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

    2015-08-01

    In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation

    USDA-ARS?s Scientific Manuscript database

    The goal of the efforts described in this dissertation was to characterize the early pathogenesis of foot-and-mouth disease (FMD) in cattle after simulated natural infection. More specifically, emphasis was placed upon two critical knowledge gaps: identification of the primary site(s) of infectio...

  11. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

    PubMed

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

    2016-08-01

    SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep

  12. Canadian patient played key role in uncovering secrets about early-onset Alzheimer's disease.

    PubMed Central

    Lyttle, J

    1996-01-01

    Last June, the University of Toronto announced that Canadian scientists and a team of international researchers had discovered the gene responsible for most cases of early-onset Alzheimer's disease. One of the key players in that discovery had died just 3 months earlier. Frances Hodge, who participated in a battery of tests for the 20 years she lived with the disease, helped lead researchers to gene S182--and an ember of hope for future generations. Images p906-a PMID:8634971

  13. Adult attachment and early parental experiences in patients with Crohn's disease.

    PubMed

    Agostini, Alessandro; Rizzello, Fernando; Ravegnani, Gianni; Gionchetti, Paolo; Tambasco, Rosy; Straforini, Giulia; Ercolani, Mauro; Campieri, Massimo

    2010-01-01

    Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease. The relationship of attachment to the illness is considered to be bidirectional. The authors investigated aspects of this bidirectional relationship. A group of 102 patients with CD and 306 healthy subjects filled out the Attachment Style Questionnaire and the Parental Bonding Instrument. Patients with CD exhibit a predominantly insecure attachment and perceived their parents' behaviors as characterized by low maternal care and high paternal overprotection. The evaluation of attachment style and early parental experiences in patients with CD may shed light on the bidirectional relationship between attachment and illness. These findings may confirm the bidirectional relationship between insecure attachment and chronic illness.

  14. 'Making the best you can of it': living with early-stage Alzheimer's disease.

    PubMed

    Macrae, Hazel

    2008-04-01

    Drawing upon data from a qualitative study of persons who are in the early stage of the condition, this paper examines the meaning of Alzheimer's disease. It contrasts the meaning of the disease as portrayed in popular culture with its meaning as interpreted by persons living with it. Findings show that persons with the illness do not necessarily accept the negative cultural meaning of the disease, nor the helpless 'victim' role in which they are generally cast. With a determination to 'make the best of it', strategies such as humour, normalisation, present-time orientation, and life review are employed to create a meaningful life.

  15. Coronary artery disease: new insights into the pathophysiology, prevalence, and early detection of a monster menace.

    PubMed

    Slater, James; Rill, Velisar

    2004-04-01

    Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the United States and other industrialized countries. In the undeveloped world a similar epidemic is brewing. A new pathophysiologic paradigm has emerged, which assigns the mediators of inflammation a much larger role in the disease process. This paradigm has helped explain the unpredictable nature of many adverse consequences of CAD. The long latent phase of the disease, and often sudden initial presentation, make efforts at early detection extremely important. Considerable work has been devoted to identify, as well as influence, predisposing risk factors for developing arteriosclerosis. Novel markers of inflammation, like C-reactive protein, have been identified and compared to traditional risk factors. In addition, new imaging modalities introduce the possibility of screening for subclinical disease. Electron beam and multidetector computed tomography (CT) scanners, as well as other techniques, are emerging as powerful tools to detect early disease presence and allow intervention to take place before major clinical events occur. Advances in our understanding of the pathophysiology of CAD, and our ability to image the stages of silent disease will go hand in hand to revolutionize our approach to prevention and treatment of this deadly malady.

  16. Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy.

    PubMed

    Zierler, S; Rothman, K J

    1985-08-08

    To clarify the association of Bendectin and other drugs used in early pregnancy with the occurrence of congenital heart disease, we interviewed 298 mothers of children with congenital heart disease and 738 mothers of healthy controls. Differential recall of drug use by mothers of affected children and mothers of controls was evaluated by comparison of information collected by interview with that recorded in the prenatal record. Data derived from maternal interviews were generally consistent with the record data. Reported Bendectin use was minimally associated with congenital heart disease (prevalence odds ratio, 1.1; 90 per cent confidence interval, 0.8 to 1.5). The data from this study were consistent with previously reported associations of other drugs with congenital heart disease. In particular, aspirin use in early pregnancy was associated with about a twofold increase in the frequency of defects in septation of the truncus arteriosus (prevalence odds ratio, 2.1; 90 per cent confidence interval, 1.1 to 3.9).

  17. The cost-effectiveness of using chronic kidney disease risk scores to screen for early-stage chronic kidney disease.

    PubMed

    Yarnoff, Benjamin O; Hoerger, Thomas J; Simpson, Siobhan K; Leib, Alyssa; Burrows, Nilka R; Shrestha, Sundar S; Pavkov, Meda E

    2017-03-13

    Better treatment during early stages of chronic kidney disease (CKD) may slow progression to end-stage renal disease and decrease associated complications and medical costs. Achieving early treatment of CKD is challenging, however, because a large fraction of persons with CKD are unaware of having this disease. Screening for CKD is one important method for increasing awareness. We examined the cost-effectiveness of identifying persons for early-stage CKD screening (i.e., screening for moderate albuminuria) using published CKD risk scores. We used the CKD Health Policy Model, a micro-simulation model, to simulate the cost-effectiveness of using CKD two published risk scores by Bang et al. and Kshirsagar et al. to identify persons in the US for CKD screening with testing for albuminuria. Alternative risk score thresholds were tested (0.20, 0.15, 0.10, 0.05, and 0.02) above which persons were assigned to receive screening at alternative intervals (1-, 2-, and 5-year) for follow-up screening if the first screening was negative. We examined incremental cost-effectiveness ratios (ICERs), incremental lifetime costs divided by incremental lifetime QALYs, relative to the next higher screening threshold to assess cost-effectiveness. Cost-effective scenarios were determined as those with ICERs less than $50,000 per QALY. Among the cost-effective scenarios, the optimal scenario was determined as the one that resulted in the highest lifetime QALYs. ICERs ranged from $8,823 per QALY to $124,626 per QALY for the Bang et al. risk score and $6,342 per QALY to $405,861 per QALY for the Kshirsagar et al. risk score. The Bang et al. risk score with a threshold of 0.02 and 2-year follow-up screening was found to be optimal because it had an ICER less than $50,000 per QALY and resulted in the highest lifetime QALYs. This study indicates that using these CKD risk scores may allow clinicians to cost-effectively identify a broader population for CKD screening with testing for albuminuria

  18. The importance of early life in childhood obesity and related diseases: a report from the 2014 Gravida Strategic Summit.

    PubMed

    Macaulay, E C; Donovan, E L; Leask, M P; Bloomfield, F H; Vickers, M H; Dearden, P K; Baker, P N

    2014-12-01

    Obesity and its related non-communicable diseases (NCDs), such as type 2 diabetes, heart disease and cancer, impose huge burdens on society, particularly the healthcare system. Until recently, public health and policy were primarily focused on secondary prevention and treatment of NCDs. However, epidemiological and experimental evidence indicates that early-life exposures influence the risk of childhood obesity and related diseases later in life, and has now focused attention on the health of both mother and child. During pregnancy and the early neonatal period, individuals respond to their environment by establishing anatomical, physiological and biochemical trajectories that shape their future health. This period of developmental plasticity provides an early window of opportunity to mitigate the environmental insults that may increase an individual's sensitivity to, or risk of, developing obesity or related diseases later in life. Although much investigation has already occurred in the area of Developmental Origins of Health and Disease research, the science itself is still in its infancy. It remains for researchers to tackle the important outstanding questions and translate their knowledge into workable solutions for the public good. The challenge, however, is to decide which areas to focus on. With these opportunities and challenges in mind, the 2014 Gravida Summit convened to examine how its early-life research program can determine which areas of research into mechanisms, biomarkers and interventions could contribute to the international research strategy to fight childhood obesity and its related diseases.

  19. Evaluation of two-test serodiagnostic method for early Lyme disease in clinical practice.

    PubMed

    Trevejo, R T; Krause, P J; Sikand, V K; Schriefer, M E; Ryan, R; Lepore, T; Porter, W; Dennis, D T

    1999-04-01

    The Centers for Disease Control and Prevention (CDC) recommend a two-test approach for the serodiagnosis of Lyme disease (LD), with EIA testing followed by Western immunoblotting (WB) of EIA-equivocal and -positive specimens. This approach was compared with a simplified two-test approach (WB of EIA equivocals only) and WB alone for early LD. Case-patients with erythema migrans (EM) rash >/=5 cm were recruited from three primary-care practices in LD-endemic areas to provide acute- (S1) and convalescent-phase serum specimens (S2). The simplified approach had the highest sensitivity when either S1 or S2 samples were tested, nearly doubling when S2 were tested, while decreasing slightly for the other two approaches. Accordingly, the simplified approach had the lowest negative likelihood ratio for either S1 or S2. For early LD with EM, the simplified approach performed well and was less costly than the other testing approaches since less WB is required.

  20. [Early interventional group therapy for patients with incipient Alzheimer disease and their relatives].

    PubMed

    Scheurich, Armin; Schanz, Benno; Müller, Matthias J; Fellgiebel, Andreas

    2008-06-01

    Pilot study on an early-interventional group therapy for patients with incipient Alzheimer disease and their relatives. The present study investigates whether scientific progress in terms of earlier time of diagnostic certainty can be used for psychoeducation, maintenance of positive activities and prevention of comorbid depressive episodes. 12 patients (66.8 +/- 5.8 years, MMSE 24.0 +/- 4.0) together with 12 relatives have been treated with a bi-weekly group therapy program. For the patients treatment resulted in reduced anxiety, anergia and withdrawal, for their relatives reduced sleep disturbances, irascibility, and aggressiveness have been found. Only one of the patients suffered from a depressive episode. All participants expressed positive feedback and a high level of quality of life. By the straightforward psychosocial intervention it seems possible to use the earlier time of diagnostic certainty for early diagnosed patients suffering from incipient Alzheimer disease. However, results have to be replicated by a controlled, prospective study with larger sample sizes.

  1. Disease Management of Early Childhood Caries: ECC Collaborative Project

    PubMed Central

    Lee, Jessica Y.

    2014-01-01

    Until recently, the standard of care for early childhood caries (ECC) has been primarily surgical and restorative treatment with little emphasis on preventing and managing the disease itself. It is now recognized that surgical treatment alone does not address the underlying etiology of the disease. Despite costly surgeries and reparative treatment, the onset and progression of caries are likely to continue. A successful rebalance of risk and protective factors may prevent, slow down, or even arrest dental caries and its progression. An 18-month risk-based chronic disease management (DM) approach to address ECC in preschool children was implemented as a quality improvement (QI) collaborative by seven teams of oral health care providers across the United States. In the aggregate, fewer DM children experienced new cavitation, pain, and referrals to the operating room (OR) for restorative treatment compared to baseline historical controls. The teams found that QI methods facilitated adoption of the DM approach and resulted in improved care to patients and better outcomes overall. Despite these successes, the wide scale adoption and spread of the DM approach may be limited unless health policy and payment reforms are enacted to compensate providers for implementing DM protocols in their practice. PMID:24723953

  2. Asynchronous (segmental early) relaxation impairs left ventricular filling in patients with coronary artery disease and normal systolic function.

    PubMed

    Vanoverschelde, J L; Wijns, W; Michel, X; Cosyns, J; Detry, J M

    1991-11-01

    Asynchronous segmental early relaxation, defined as a localized early segmental outward motion of the left ventricular endocardium during isovolumetric relaxation, has been associated with an altered left ventricular relaxation rate. To determine whether asynchronous segmental early relaxation also results in impaired left ventricular filling, early diastolic ventricular wall motion and Doppler-derived left ventricular filling indexes were examined in 25 patients with documented coronary artery disease and normal systolic function. Patients were further classified into two groups according to the presence (n = 15, group 1) or absence (n = 10, group 2) of asynchronous early relaxation at left ventriculography. A third group of 10 age-matched normal subjects served as a control group. No differences were observed between the two patient groups with coronary artery disease with respect to age, gender distribution, heart rate, left ventricular systolic and diastolic pressures or extent and severity of coronary artery disease. No differences in transmitral filling dynamics were observed between group 2 patients and age-matched control subjects. Conversely, group 1 patients had significantly lower peak early filling velocities (44 +/- 11 vs. 58 +/- 11 cm/s, p less than 0.01), larger atrial filling fraction (45 +/- 4% vs. 38 +/- 4%, p less than 0.001), lower ratio of early to late transmitral filling velocities (0.6 +/- 0.08 vs. 0.99 +/- 0.18, p less than 0.001) and a longer isovolumetric relaxation period (114 +/- 12 vs. 90 +/- 6 ms, p less than 0.001) compared with group 2 patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Arm swing magnitude and asymmetry during gait in the early stages of Parkinson's disease.

    PubMed

    Lewek, Michael D; Poole, Roxanne; Johnson, Julia; Halawa, Omar; Huang, Xuemei

    2010-02-01

    The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in "off" state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p = 0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p = 0.907) or less (p = 0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9 + or - 7.9%) compared to the control group (asymmetry angle: 5.1 + or - 4.0%; p = 0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD. Copyright 2009 Elsevier B.V. All rights reserved.

  4. Arm Swing Magnitude and Asymmetry During Gait in the Early Stages of Parkinson's Disease

    PubMed Central

    Lewek, Michael D.; Poole, Roxanne; Johnson, Julia; Halawa, Omar; Huang, Xuemei

    2009-01-01

    The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in “off” state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p=0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p=0.907) or less (p=0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9±7.9%) compared to the control group (asymmetry angle: 5.1±4.0%; p=0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD. PMID:19945285

  5. Symptoms to pollen and fruits early in life and allergic disease at 4 years of age.

    PubMed

    Mai, X-M; Neuman, A; Ostblom, E; Pershagen, G; Nordvall, L; Almqvist, C; van Hage, M; Wickman, M

    2008-11-01

    The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1-9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4). The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease.

  6. Chronic lung disease of prematurity and early childhood wheezing: is foetal inflammatory response syndrome to blame?

    PubMed

    Dessardo, Nada Sindičić; Dessardo, Sandro; Mustać, Elvira; Banac, Srđan; Petrović, Oleg; Peter, Branimir

    2014-09-01

    Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. We aimed to investigate the perinatal and maternal risk factors involved in the development of chronic respiratory morbidity in preterm infants, with an emphasis on the importance of Foetal Inflammatory Response Syndrome (FIRS). Prospective cohort study. Demographic, antenatal, delivery and outcomes data were collected from 262 infants with less than 32 completed weeks of gestational age, over a 10-year period. Presence of chronic lung disease of prematurity and early childhood wheezing. In multivariate logistic regression analysis the presence of FIRS appears to be the most important risk factor for both, chronic lung disease of prematurity (OR 31.05, 95% CI 10.7-87.75, p<0.001) and early childhood wheezing (OR 5.63, 95% CI 2.42-13.05, p=0.01). In the alternative regression model for early childhood wheezing, with chronic lung disease included as a variable, the statistical significance of FIRS completely vanished (OR 1.15, 95% CI 0.39-3.34, p=0.79), whilst chronic lung disease became the most important risk factor (OR 23.45, 95% CI 8.5-63.25, p<0.001). Prenatal and early neonatal events are of utmost importance in the development of chronic respiratory symptoms in children. The influence of FIRS on the development of chronic respiratory symptoms goes far beyond its impact on gestational age and may be related to direct inflammation-mediated lung tissue damage. CLD appears to be an intermittent step on the way from FIRS to ECW. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Reproductive Toxicity of T Cells in Early Life: Abnormal Immune Development and Postnatal Diseases.

    PubMed

    Liu, Han-Xiao; Jiang, Aifang; Chen, Ting; Qu, Wen; Yan, Hui-Yi; Ping, Jie

    2017-01-01

    Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent researches have pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life. Epidemiological and experimental studies showed an inseparable relationship between T cell developmental toxicity and immune diseases in adults. Considering that the inflammatory and immune disorders have become a growing health problem worldwide, increasing attention is now being paid to the T cell developmental toxicity. We propose that adverse factors may have programming effects on the crucial functions of immune system during early life which is critical for fetal T cell development and the establishment of the distinct T cell repertoires balance. The permanently disturbed intrathymic or peripheral T cell development may in turn lead to the immune disorders in later life. In this manuscript, we reviewed how adverse factors affected T cell development in early-life with the consequence of the immune dysfunction and immune diseases, and further elucidate the mechanisms. These mechanisms will be helpful in prevention and treatment of the increased prevalence of immune diseases by interfering those pathways. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Hormone response to bidirectional selection on social behavior.

    PubMed

    Amdam, Gro V; Page, Robert E; Fondrk, M Kim; Brent, Colin S

    2010-01-01

    Behavior is a quantitative trait determined by multiple genes. Some of these genes may have effects from early development and onward by influencing hormonal systems that are active during different life-stages leading to complex associations, or suites, of traits. Honey bees (Apis mellifera) have been used extensively in experiments on the genetic and hormonal control of complex social behavior, but the relationships between their early developmental processes and adult behavioral variation are not well understood. Bidirectional selective breeding on social food-storage behavior produced two honey bee strains, each with several sublines, that differ in an associated suite of anatomical, physiological, and behavioral traits found in unselected wild type bees. Using these genotypes, we document strain-specific changes during larval, pupal, and early adult life-stages for the central insect hormones juvenile hormone (JH) and ecdysteroids. Strain differences correlate with variation in female reproductive anatomy (ovary size), which can be influenced by JH during development, and with secretion rates of ecdysteroid from the ovaries of adults. Ovary size was previously assigned to the suite of traits of honey bee food-storage behavior. Our findings support that bidirectional selection on honey bee social behavior acted on pleiotropic gene networks. These networks may bias a bee's adult phenotype by endocrine effects on early developmental processes that regulate variation in reproductive traits. © 2010 Wiley Periodicals, Inc.

  9. Impact of DNA testing for early-onset familial Alzheimer disease and frontotemporal dementia.

    PubMed

    Steinbart, E J; Smith, C O; Poorkaj, P; Bird, T D

    2001-11-01

    DNA testing of persons at risk for hereditary, degenerative neurologic diseases is relatively new. Only anecdotal reports of such testing in familial Alzheimer disease (FAD) exist, and little is know about the personal and social impact of such testing. In a descriptive, observational study, individuals at 50% risk for autosomal dominant, early-onset FAD or frontotemporal dementia with parkinsonism linked to chromosome 17 underwent DNA testing for the genetic mutations previously identified in affected family members. Individuals were followed up for (1/2) to 3 years and were interviewed regarding attitudes toward the testing process and the impact of the results. Twenty-one (8.4%) of 251 persons at risk for FAD or frontotemporal dementia requested genetic testing. The most common reasons for requesting testing were concern about early symptoms of dementia, financial or family planning, and relief from anxiety. Twelve individuals had positive DNA test results, and 6 of these had early symptoms of dementia; 8 had negative results; and 1 has not yet received results. Of 14 asymptomatic individuals completing testing, 13 believed the testing was beneficial. Two persons reported moderate anxiety and 1 reported moderate depression. As expected, persons with negative test results had happier experiences overall, but even they had to deal with ongoing anxiety and depression. Thus far, there have been no psychiatric hospitalizations, suicide attempts, or denials of insurance. Genetic testing in early-onset FAD and frontotemporal dementia can be completed successfully. Most individuals demonstrate effective coping skills and find the testing to be beneficial, but long-term effects remain unknown.

  10. Early polymerase chain reaction detection of Chagas disease reactivation in heart transplant patients.

    PubMed

    da Costa, Priscilla Almeida; Segatto, Marcela; Durso, Danielle Fernandes; de Carvalho Moreira, Wagson José; Junqueira, Lucas Lodi; de Castilho, Fábio Morato; de Andrade, Silvio Amadeu; Gelape, Cláudio Léo; Chiari, Egler; Teixeira-Carvalho, Andréa; Junho Pena, Sergio Danilo; Machado, Carlos Renato; Franco, Gloria Regina; Filho, Geraldo Brasileiro; Vieira Moreira, Maria da Consolação; Mara Macedo, Andréa

    2017-07-01

    Heart transplantation is a valuable therapeutic option for Chagas disease patients with severe cardiomyopathy. During patient follow-up, the differential diagnosis between cardiac transplant rejection and Chagas disease infection reactivation remains a challenging task, which hinders rapid implementation of the appropriate treatment. Herein we investigate whether polymerase chain reaction (PCR) strategies could facilitate early detection of Trypanosoma cruzi (T cruzi) in transplanted endomyocardial biopsies (EMBs). In this study we analyzed 500 EMB specimens obtained from 58 chagasic cardiac transplant patients, using PCR approaches targeted to nuclear (rDNA 24Sα) and kinetoplastid (kDNA) markers, and compared the efficiency of these approaches with that of other tests routinely used. T cruzi DNA was detected in 112 EMB specimens derived from 39 patients (67.2%). The first positive result occurred at a median 1.0 month post-transplant. Conventional histopathologic, blood smear and hemoculture analyses showed lower sensitivity and higher median time to the first positive result. Patient follow-up revealed that 31 of 39 PCR-positive cases presented clinical reactivation of Chagas disease at different time-points after transplantation. PCR techniques showed considerable sensitivity (0.82) and specificity (0.60), with area under the receiver operating characteristic (ROC) curves of 0.708 (p = 0.001). Moreover, PCR techniques anticipated the clinical signs of Chagas disease reactivation by up to 36 months, with a median time of 6 months and an average of 9.1 months. We found a good association between the PCR diagnosis and the clinical signs of the disease, indicating that the PCR approaches used herein are suitable for early diagnosis of Chagas disease reactivation, with high potential to assist physicians in treatment decisions. For this purpose, an algorithm is proposed for surveillance based on the molecular tests. Copyright © 2017 International Society for the

  11. [The application of the prospective space-time statistic in early warning of infectious disease].

    PubMed

    Yin, Fei; Li, Xiao-Song; Feng, Zi-Jian; Ma, Jia-Qi

    2007-06-01

    To investigate the application of prospective space-time scan statistic in the early stage of detecting infectious disease outbreaks. The prospective space-time scan statistic was tested by mimicking daily prospective analyses of bacillary dysentery data of Chengdu city in 2005 (3212 cases in 102 towns and villages). And the results were compared with that of purely temporal scan statistic. The prospective space-time scan statistic could give specific messages both in spatial and temporal. The results of June indicated that the prospective space-time scan statistic could timely detect the outbreaks that started from the local site, and the early warning message was powerful (P = 0.007). When the merely temporal scan statistic for detecting the outbreak was sent two days later, and the signal was less powerful (P = 0.039). The prospective space-time scan statistic could make full use of the spatial and temporal information in infectious disease data and could timely and effectively detect the outbreaks that start from the local sites. The prospective space-time scan statistic could be an important tool for local and national CDC to set up early detection surveillance systems.

  12. Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers.

    PubMed

    García-Blanco, Ana; Peña-Bautista, Carmen; Oger, Camille; Vigor, Claire; Galano, Jean-Marie; Durand, Thierry; Martín-Ibáñez, Nuria; Baquero, Miguel; Vento, Máximo; Cháfer-Pericás, Consuelo

    2018-07-01

    Lipid peroxidation plays an important role in Alzheimer Disease, so corresponding metabolites found in urine samples could be potential biomarkers. The aim of this work is to develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry analytical method to determine a new set of lipid peroxidation compounds in urine samples. Excellent sensitivity was achieved with limits of detection between 0.08 and 17 nmol L -1 , which renders this method suitable to monitor analytes concentrations in real samples. The method's precision was satisfactory with coefficients of variation around 5-17% (intra-day) and 8-19% (inter-day). The accuracy of the method was assessed by analysis of spiked urine samples obtaining recoveries between 70% and 120% for most of the analytes. The utility of the described method was tested by analyzing urine samples from patients early diagnosed with mild cognitive impairment or mild dementia Alzheimer Disease following the clinical standard criteria. As preliminary results, some analytes (17(RS)-10-epi-SC-Δ 15 -11-dihomo-IsoF, PGE 2 ) and total parameters (Neuroprostanes, Isoprostanes, Isofurans) show differences between the control and the clinical groups. So, these analytes could be potential early Alzheimer Disease biomarkers assessing the patients' pro-oxidant condition. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Low clinical diagnostic accuracy of early vs advanced Parkinson disease: clinicopathologic study.

    PubMed

    Adler, Charles H; Beach, Thomas G; Hentz, Joseph G; Shill, Holly A; Caviness, John N; Driver-Dunckley, Erika; Sabbagh, Marwan N; Sue, Lucia I; Jacobson, Sandra A; Belden, Christine M; Dugger, Brittany N

    2014-07-29

    Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard. Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, PossPD (never treated or not clearly responsive) and ProbPD (responsive to medications). Neuropathologic diagnosis was the gold standard. Based on first visit, 9 of 34 (26%) PossPD cases had neuropathologically confirmed PD while 80 of 97 (82%) ProbPD cases had confirmed PD. PD was confirmed in 8 of 15 (53%) ProbPD cases with <5 years of disease duration and 72 of 82 (88%) with ≥5 years of disease duration. Using final diagnosis at time of death, 91 of 107 (85%) ProbPD cases had confirmed PD. Clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias, and hyposmia. Using neuropathologic findings of PD as the gold standard, this study establishes the novel findings of only 26% accuracy for a clinical diagnosis of PD in untreated or not clearly responsive subjects, 53% accuracy in early PD responsive to medication (<5 years' duration), and >85% diagnostic accuracy of longer duration, medication-responsive PD. Caution is needed when interpreting clinical studies of PD, especially studies of early disease that do not have autopsy confirmation. The need for a tissue or other diagnostic biomarker is reinforced. This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%. © 2014 American Academy of Neurology.

  14. Median network analysis of defectively sequenced entire mitochondrial genomes from early and contemporary disease studies.

    PubMed

    Bandelt, Hans-Jürgen; Yao, Yong-Gang; Bravi, Claudio M; Salas, Antonio; Kivisild, Toomas

    2009-03-01

    Sequence analysis of the mitochondrial genome has become a routine method in the study of mitochondrial diseases. Quite often, the sequencing efforts in the search of pathogenic or disease-associated mutations are affected by technical and interpretive problems, caused by sample mix-up, contamination, biochemical problems, incomplete sequencing, misdocumentation and insufficient reference to previously published data. To assess data quality in case studies of mitochondrial diseases, it is recommended to compare any mtDNA sequence under consideration to their phylogenetically closest lineages available in the Web. The median network method has proven useful for visualizing potential problems with the data. We contrast some early reports of complete mtDNA sequences to more recent total mtDNA sequencing efforts in studies of various mitochondrial diseases. We conclude that the quality of complete mtDNA sequences generated in the medical field in the past few years is somewhat unsatisfactory and may even fall behind that of pioneer manual sequencing in the early nineties. Our study provides a paradigm for an a posteriori evaluation of sequence quality and for detection of potential problems with inferring a pathogenic status of a particular mutation.

  15. Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease

    PubMed Central

    Uhde, Melanie; Ajamian, Mary; Li, Xueting; Wormser, Gary P.; Marques, Adriana; Alaedini, Armin

    2016-01-01

    Background. Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis. Methods. Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups. Results. CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome. Conclusions. These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection. PMID:27585799

  16. The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer.

    PubMed

    Nicklin, James; Janda, Monika; Gebski, Val; Jobling, Thomas; Land, Russell; Manolitsas, Tom; McCartney, Anthony; Nascimento, Marcelo; Perrin, Lewis; Baker, Jannah F; Obermair, Andreas

    2012-08-15

    Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer. Copyright © 2011 UICC.

  17. Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease.

    PubMed

    Uhde, Melanie; Ajamian, Mary; Li, Xueting; Wormser, Gary P; Marques, Adriana; Alaedini, Armin

    2016-12-01

     Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis.  Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups.  CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.  These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age.

    PubMed

    de Meer, G; Janssen, N A H; Brunekreef, B

    2005-05-01

    There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions. Examine independent effects on atopic sensitization and symptoms of day care attendance, older siblings, pet ownership, and early infancy's airway disease. A cross-sectional survey among 8-13-year-old school children with complete data for 1555 children. After adjustment for confounders, atopic sensitization occurred less frequently in children that had attended a day care centre (OR: 0.73, 95% CI: 0.55-0.98) or had a cat or dog before 2 years of age (OR: 0.78, 95% CI: 0.61-0.99). Having older siblings yielded a nonsignificant trend towards protection (OR: 0.88, 95% CI: 0.70-1.11). For symptoms, there was no relation with having older sibs, day care attendance and pet ownership, although there was a trend towards protection for the combination of atopy and symptoms. In contrast, children with doctors' treated airway disease before age 2, more frequently reported recent symptoms of wheeze, asthma, rhinitis, or dermatitis (all P < 0.05). Early life environmental exposure to day care, or pets may protect against atopic sensitization. Protection against symptoms only occurred if atopic sensitization was present as well.

  19. Early identification and treatment of communication and swallowing deficits in Parkinson disease.

    PubMed

    Ciucci, Michelle R; Grant, Laura M; Rajamanickam, Eunice S Paul; Hilby, Breanna L; Blue, Katherine V; Jones, Corinne A; Kelm-Nelson, Cynthia A

    2013-08-01

    Parkinson disease (PD) is a complex, progressive, neurodegenerative disorder that leads to a wide range of deficits including fine and gross sensorimotor impairment, autonomic dysfunction, mood disorders, and cognitive decline. Traditionally, the focus for diagnosis and treatment has been on sensorimotor impairment related to dopamine depletion. It is now widely recognized, however, that PD-related pathology affects multiple central nervous system neurotransmitters and pathways. Communication and swallowing functions can be impaired even in the early stages, significantly affecting health and quality of life. The purpose of this article is to review the literature on early intervention for communication and swallowing impairment in PD. Overarching themes were that (1) studies and interpretation of data from studies in early PD are limited; (2) best therapy practices have not been established, in part due to the heterogeneous nature of PD; and (3) as communication and swallowing problems are pervasive in PD, further treatment research is essential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Early Identification and Treatment of Communication and Swallowing Deficits in Parkinson Disease

    PubMed Central

    Ciucci, Michelle R.; Grant, Laura M.; Paul Rajamanickam, Eunice S.; Hilby, Breanna L.; Blue, Katherine V.; Jones, Corinne A.; Kelm-Nelson, Cynthia A.

    2015-01-01

    Parkinson disease (PD) is a complex, progressive, neurodegenerative disorder that leads to a wide range of deficits including fine and gross sensorimotor impairment, autonomic dysfunction, mood disorders, and cognitive decline. Traditionally, the focus for diagnosis and treatment has been on sensorimotor impairment related to dopamine depletion. It is now widely recognized, however, that PD-related pathology affects multiple central nervous system neurotransmitters and pathways. Communication and swallowing functions can be impaired even in the early stages, significantly affecting health and quality of life. The purpose of this article is to review the literature on early intervention for communication and swallowing impairment in PD. Overarching themes were that (1) studies and interpretation of data from studies in early PD are limited; (2) best therapy practices have not been established, in part due to the heterogeneous nature of PD; and (3) as communication and swallowing problems are pervasive in PD, further treatment research is essential. PMID:24166192

  1. Discourse changes in early Alzheimer disease, mild cognitive impairment, and normal aging.

    PubMed

    Chapman, Sandra Bond; Zientz, Jennifer; Weiner, Myron; Rosenberg, Roger; Frawley, William; Burns, Mary Hope

    2002-01-01

    The purpose of this study was to determine the sensitivity of discourse gist measures to the early cognitive-linguistic changes in Alzheimer disease (AD) and in the preclinical stages. Differences in discourse abilities were examined in 25 cognitively normal adults, 24 adults with mild probable AD, and 20 adults with mild cognitive impairment (MCI) at gist and detail levels of discourse processing. The authors found that gist and detail levels of discourse processing were significantly impaired in persons with AD and MCI as compared with normal control subjects. Gist-level discourse processing abilities showed minimal overlap between cognitively normal control subjects and those with mild AD. Moreover, the majority of the persons with MCI performed in the range of AD on gist measures. These findings indicate that discourse gist measures hold promise as a diagnostic complement to enhance early detection of AD. Further studies are needed to determine how early the discourse gist deficits arise in AD.

  2. Treponemal disease in the middle Archaic to early Woodland periods of the western Tennessee River Valley.

    PubMed

    Smith, Maria Ostendorf

    2006-10-01

    The high frequency of late prehistoric New World treponemal disease is attributable to the demographic changes concomitant with the adoption of agriculture. However, these demographic changes in group mobility and site density episodically preceded intensive plant domestication, suggesting possible staggered temporal change in observed treponemal disease case frequency. Thirteen convincing and an additional two probable (N = 581) cases of treponemal disease were identified in an eight-site skeletal sample spanning the Middle (6,000-3,000 BCE) to Late (2,500-ca. 1,000 to 500 BCE) Archaic and Early Woodland (500 BCE-0 CE) periods from the western Tennessee River Valley. Treponemal disease cases are infrequent in both the Middle (3/115, 2.6%) and Late (2 to 4 cases, Early Woodland horizon. As the subsistence economy across the Archaic-Woodland temporal boundary in the western Tennessee River Valley remained, as elsewhere, based on intensive hunting and collecting, the demographic corollaries of treponemal disease would apparently not be met. However, the traditional horizon marker of the Woodland period is the adoption of pottery, an activity associated with sedentism.

  3. Non-invasive assessment determine the swallowing and respiration dysfunction in early Parkinson's disease.

    PubMed

    Wang, Chin-Man; Shieh, Wann-Yun; Weng, Yi-Hsin; Hsu, Yi-Hsuan; Wu, Yih-Ru

    2017-09-01

    Dysphagia is common among patients with Parkinson's disease. Swallowing and its coordination with respiration is extremely important to achieve safety swallowing. Different tools have been used to assess this coordination, however the results have been inconsistent. We aimed to investigate this coordination in patients with Parkinson's disease using a non-invasive method. Signals of submental muscle activity, thyroid cartilage excursion, and nasal airflow during swallowing were recorded simultaneously. Five different water boluses were swallowed three times, and the data were recorded and analyzed. Thirty-seven controls and 42 patients with early-stage Parkinson's disease were included. The rates of non-expiratory/expiratory pre- and post-swallowing respiratory phase patterns were higher in the patients than in the controls (P < 0.001). The rates of piecemeal deglutition when swallowing 10-ml and 20-ml water boluses and overall were also significantly higher in the patients (all P < 0.001). There were differences in oropharyngeal swallowing parameters between the patients and controls, including a pharyngeal phase delay with longer total excursion duration and excursion time in the patients swallowing small water boluses (1 ml, 3 ml and 5 ml), but no difference in the length of swallowing respiratory pause. Oropharyngeal swallowing and its coordination with respiration are affected in patients with early-stage Parkinson's disease, and safety compensation mechanisms were used more than efficiency during swallowing. The results of this study may serve as a baseline for further research into new treatment regimens and to improve the management of swallowing in patients with Parkinson's disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. The prevention of early-onset neonatal group B streptococcal disease.

    PubMed

    Money, Deborah M; Dobson, Simon

    2004-09-01

    To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal (GBS) disease. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. A review of the literature through MEDLINE from January 1980 to December 2003, relating to neonatal group B streptococcal infection and a review of the Centers for Disease Control and Prevention recommendations. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on the Periodic Health Exam. 1. Offer all women screening for group B streptococcal disease at 35 to 37 weeks' gestation with culture done from one swab first to the vagina then to the rectal area. (II-1)2. Treat the following women intrapartum at time of labour or rupture of membranes with IV antibiotics: -all women positive by GBS culture screening done at 35 to 37 weeks (II-2) - any women with an infant previously infected with GBS (II-3) - any women with documented GBS bacteriuria (regardless of level of colony-forming units per mL) in this pregnancy (II-2) 3. Treat women at less than 37 weeks' gestation with IV antibiotics unless there has been a negative GBS vaginal/rectal swab culture within 5 weeks. (II-3) 4. Treat women with intrapartum fever with IV antibiotics (i.e., chorioamnionitis must be treated, but broader spectrum antibiotics would be advised). (II-2) 5. If a woman is GBS-positive by culture screening or by history of bacteriuria, with prelabour rupture of membranes at term, treat with GBS antibiotic prophylaxis and initiate induction of

  5. Restless legs syndrome: an early clinical feature of Parkinson disease in men.

    PubMed

    Wong, Janice C; Li, Yanping; Schwarzschild, Michael A; Ascherio, Alberto; Gao, Xiang

    2014-02-01

    The association between restless legs syndrome (RLS) and Parkinson disease has been extensively studied, but the temporal relationship between the two remains unclear. We thus conduct the first prospective study to examine the risk of developing Parkinson disease in RLS. Prospective study from 2002-2010. United States. There were 22,999 US male health professionals age 40-75 y enrolled in the Health Professionals Follow-up Study without Parkinson disease, arthritis, or diabetes mellitus at baseline. RLS was assessed in 2002 using a set of standardized questions recommended by the International RLS Study Group. Incident Parkinson disease was identified by biennial questionnaires and then confirmed by review of participants' medical records by a movement disorder specialist. We documented 200 incident Parkinson disease cases during 8 y of follow-up. Compared to men without RLS, men with RLS symptoms who had symptoms greater than 15 times/mo had higher risk of Parkinson disease development (adjusted relative risk = 1.47; 95% confidence interval: 0.59, 3.65; P = 0.41). This was statistically significant only for cases diagnosed within 4 y of follow-up (adjusted relative risk = 2.77; 95% confidence interval: 1.08, 7.11; P = 0.03). Severe restless legs syndrome may be an early feature of Parkinson disease.

  6. Early growth and chronic disease: a public health overview.

    PubMed

    Law, Catherine

    2005-07-01

    Infant and childhood growth result from and reflect a range of influences in pre- and postnatal life. These include nutrition, burden of infection and the psycho-social environment. Nutrition in young children is dependent on individual level factors such as fetal experience, infant feeding and weaning practices, and on societal factors such as education of women and economic conditions. The relationship of early postnatal growth to adult disease may be indicative or causal, and may reveal both biological and sociological processes. Although non-insulin-dependent diabetes mellitus (NIDDM) and obesity are risk factors for ischaemic heart disease, the relationships of these three conditions to infant growth differ. Poor infant growth has been associated with higher levels of NIDDM and ischaemic heart disease, but lower levels of adult obesity. Most research has been of populations living in developed countries at different stages of nutritional transition. However, differences in context are not simply limited to the stage of the nutritional transition. They also need to consider the nature of that transition and its social correlates, which may result in the clustering of aetiological influences such as increased body mass and poverty. The size of effect of the relationship of infant growth to adult disease is important not only to determine its relative aetiological importance but also for its potential for public health policy. Such policy also needs to consider the relationships of infant growth to a range of outcomes, both health and human capital, which are not the subject of this workshop.

  7. An early and late peak in microglial activation in Alzheimer's disease trajectory.

    PubMed

    Fan, Zhen; Brooks, David J; Okello, Aren; Edison, Paul

    2017-03-01

    Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease. Thirty subjects (eight mild cognitive impairment, eight Alzheimer's disease and 14 controls) aged between 54 and 77 years underwent 11C-(R)PK11195, 11C-PIB positron emission tomography and magnetic resonance imaging scans. Patients were followed-up after 14 ± 4 months. Region of interest and Statistical Parametric Mapping analysis were used to determine longitudinal alterations. Single subject analysis was performed to evaluate the individualized pathological changes over time. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed using Biological Parametric Mapping. We demonstrated that both baseline and follow-up microglial activation in the mild cognitive impairment cohort compared to controls were increased by 41% and 21%, respectively. There was a longitudinal reduction of 18% in microglial activation in mild cognitive impairment cohort over 14 months, which was associated with a mild elevation in fibrillar amyloid load. Cortical clusters of microglial activation and amyloid deposition spatially overlapped in the subjects with mild cognitive impairment. Baseline microglial activation was increased by 36% in Alzheimer's disease subjects compared with controls. Longitudinally, Alzheimer's disease subjects showed

  8. Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease

    PubMed Central

    Weiner, Zachary P.; Crew, Rebecca M.; Brandt, Kevin S.; Ullmann, Amy J.; Schriefer, Martin E.; Molins, Claudia R.

    2015-01-01

    Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. PMID:26376927

  9. Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease.

    PubMed

    Weiner, Zachary P; Crew, Rebecca M; Brandt, Kevin S; Ullmann, Amy J; Schriefer, Martin E; Molins, Claudia R; Gilmore, Robert D

    2015-11-01

    Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Deep Brain Stimulation in Early Parkinson’s Disease: Enrollment Experience from a Pilot Trial

    PubMed Central

    Charles, PD; Dolhun, RM; Gill, CE; Davis, TL; Bliton, MJ; Tramontana, MG; Salomon, RM; Wang; Hedera, P; Phibbs, FT; Neimat, JS; Konrad, PE

    2011-01-01

    Background Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson’s disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression. Methods We are conducting a prospective, randomized, single-blind clinical trial of optimal drug therapy (ODT) compared to medication plus DBS (ODT + DBS) in subjects with Hoehn & Yahr Stage II idiopathic PD who are without motor fluctuations or dementia. We report here subject screening, enrollment, baseline characteristics, and adverse events. Results 30 subjects (average age 60 ± 6.9 years, average duration of medicine 2.1 ± 1.3 years, average UPDRS-III scores 14.9 on medication and 27.0 off medication) are enrolled in the ongoing study. Twelve of 15 subjects randomized to DBS experienced perioperative adverse events, the majority of which were related to the procedure or device and resolved without sequelae. Frequently reported adverse events included wound healing problems, headache, edema, and confusion. Conclusion This report demonstrates that subjects with early stage PD can be successfully recruited, consented and retained in a long term clinical trial of DBS. Our ongoing pilot investigation will provide important preliminary safety and tolerability data concerning the application of DBS in early stage PD. PMID:22104012

  11. Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

    PubMed Central

    Roy, Dheeraj S.; Arons, Autumn; Mitchell, Teryn I.; Pignatelli, Michele; Ryan, Tomás J.; Tonegawa, Susumu

    2016-01-01

    Summary Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions1. Memory decline in early stages of Alzheimer’s is mostly limited to episodic memory, for which the hippocampus (HPC) plays a crucial role2. However, it has been uncertain whether the observed amnesia in early stages of Alzheimer’s is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early Alzheimer’s, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are utilized, revealing a retrieval, rather than a storage impairment. Prior to amyloid plaque deposition, the amnesia in these mice is age-dependent3–5, which correlates with a progressive reduction of spine density of hippocampal dentate gyrus (DG) engram cells. We show that optogenetic induction of long-term potentiation (LTP) at perforant path (PP) synapses of DG engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of DG engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in early stages of Alzheimer’s disease. PMID:26982728

  12. [Early diagnosis of Hansen disease: study of the health services in Recife (Pernambuco), Brazil].

    PubMed

    Feliciano, K V; Kovacs, M H; Alzate, A

    1998-07-01

    This paper presents the results of a descriptive study carried out in the city of Recife, state of Pernambuco, Brazil, between March and September 1994. The study aimed at health services available for performing early diagnosis of Hansen's disease with emphasis on accessibility and quality of the services provided. The sample consisted of 32 health clinics visited for diagnostic purposes by 183 patients with Hansen's disease. Information on organizational infrastructures was collected by means of interviews with health clinic managers. Information regarding routine procedures in the 32 clinics was collected by observation, with special attention given to archival and inspection activities. A total of 1,998 patients were interviewed to determine accessibility of services. Time spent in consultation with the physician was determined for 1,000 patients who were seen by 123 physicians at the clinics during the interviews. To explore physicians' attitude and knowledge regarding Hansen's disease, 133 were randomly selected from a list of names. The following factors were identified as hindering early diagnosis of Hansen's disease: the large number of people seeking service who could not be seen by a physician on the same day; the long time elapsed between appointment scheduling and the actual visit (for those not seen on the same day); the long wait for the consultation; the brevity of the consultation; the low availability of trained personnel; the low proportion of physicians who examined all body surfaces; difficulties in the clinical recognition of the disease; and physicians not prepared to make a differential diagnosis. These obstacles can precipitate the physical deterioration of Hansen's disease patients and stimulate the persistence of transmissibility; therefore, they need to be overcome if Hansen's disease is to be eliminated.

  13. Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

    PubMed Central

    Brown, Traci A.; Holian, Andrij; Pinkerton, Kent E.; Lee, Joong Won; Cho, Yoon Hee

    2016-01-01

    Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development. PMID:27138493

  14. Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

    PubMed

    Brown, Traci Ann; Holian, Andrij; Pinkerton, Kent E; Lee, Joong Won; Cho, Yoon Hee

    2016-07-01

    Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

  15. Breath analysis system for early detection of lung diseases based on multi-sensor array

    NASA Astrophysics Data System (ADS)

    Jeon, Jin-Young; Yu, Joon-Boo; Shin, Jeong-Suk; Byun, Hyung-Gi; Lim, Jeong-Ok

    2013-05-01

    Expiratory breath contains various VOCs(Volatile Organic Compounds) produced from the human. When a certain disease exists, the exhalation has specific VOCs which may be generated from diseases. Many researchers have been actively working to find different types of biomarkers which are characteristic for particular diseases. Research regarding the identification of specific diseases from exhalation is still in progress. The aim of this research is to implement early detection of lung disease such as lung cancer and COPD(Chronic Obstructive Pulmonary Disease), which was nominated on the 6th of domestic death rate in 2010, based on multi-sensor array system. The system has been used to acquire sampled expiratory gases data and PCA(Principle Component Analysis) technique was applied to analyze signals from multi-sensor array. Throughout the experimental trials, a clearly distinguishable difference between lung disease patients and healthy controls was found from the measurement and analysis of their respective expiratory gases.

  16. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

    PubMed Central

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.

    2016-01-01

    Abstract See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye

  17. Determination of minimal clinically important change in early and advanced Parkinson's disease.

    PubMed

    Hauser, Robert A; Auinger, Peggy

    2011-04-01

    Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. Copyright © 2011 Movement Disorder Society.

  18. Cortical atrophy patterns in early Parkinson's disease patients using hierarchical cluster analysis.

    PubMed

    Uribe, Carme; Segura, Barbara; Baggio, Hugo Cesar; Abos, Alexandra; Garcia-Diaz, Anna Isabel; Campabadal, Anna; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Tolosa, Eduard; Junque, Carme

    2018-05-01

    Cortical brain atrophy detectable with MRI in non-demented advanced Parkinson's disease (PD) is well characterized, but its presence in early disease stages is still under debate. We aimed to investigate cortical atrophy patterns in a large sample of early untreated PD patients using a hypothesis-free data-driven approach. Seventy-seven de novo PD patients and 50 controls from the Parkinson's Progression Marker Initiative database with T1-weighted images in a 3-tesla Siemens scanner were included in this study. Mean cortical thickness was extracted from 360 cortical areas defined by the Human Connectome Project Multi-Modal Parcellation version 1.0, and a hierarchical cluster analysis was performed using Ward's linkage method. A general linear model with cortical thickness data was then used to compare clustering groups using FreeSurfer software. We identified two patterns of cortical atrophy. Compared with controls, patients grouped in pattern 1 (n = 33) were characterized by cortical thinning in bilateral orbitofrontal, anterior cingulate, and lateral and medial anterior temporal gyri. Patients in pattern 2 (n = 44) showed cortical thinning in bilateral occipital gyrus, cuneus, superior parietal gyrus, and left postcentral gyrus, and they showed neuropsychological impairment in memory and other cognitive domains. Even in the early stages of PD, there is evidence of cortical brain atrophy. Neuroimaging clustering analysis is able to detect two subgroups of cortical thinning, one with mainly anterior atrophy, and the other with posterior predominance and worse cognitive performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients.

    PubMed

    Li, Rui; Dai, Jinna; Kang, Hui

    2018-03-01

    Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC-MS/MS on MRM (+) mode. Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin-c. Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early-stage chronic kidney disease. © 2017 Wiley Periodicals, Inc.

  20. Subjective cognitive impairment: Towards early identification of Alzheimer disease.

    PubMed

    Garcia-Ptacek, S; Eriksdotter, M; Jelic, V; Porta-Etessam, J; Kåreholt, I; Manzano Palomo, S

    2016-10-01

    Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. Lack of information about the early pathophysiology in AD complicates the search for therapeutic strategies.Subjective cognitive impairment is the description given to subjects who have memory-related complaints without pathological results on neuropsychological tests. There is no consensus regarding this heterogeneous syndrome, but at least some of these patients may represent the earliest stage in AD. We reviewed available literature in order to summarise current knowledge on subjective cognitive impairment. Although they may not present detectable signs of disease, SCI patients as a group score lower on neuropsychological tests than the general population does, and they also have a higher incidence of future cognitive decline. Depression and psychiatric co-morbidity play a role but cannot account for all cognitive complaints. Magnetic resonance imaging studies in these patients reveal a pattern of hippocampal atrophy similar to that of amnestic mild cognitive impairment and functional MRI shows increased activation during cognitive tasks which might indicate compensation for loss of function. Prevalence of an AD-like pattern of beta-amyloid (Aβ42) and tau proteins in cerebrospinal fluid is higher in SCI patients than in the general population. Memory complaints are relevant symptoms and may predict AD. Interpatient variability and methodological differences between clinical studies make it difficult to assign a definition to this syndrome. In the future, having a standard definition and longitudinal studies with sufficient follow-up times and an emphasis on quantifiable variables may clarify aspects of early AD. Copyright © 2012 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

    PubMed

    Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

    2010-08-01

    The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Effects of TORC1 Inhibition during the Early and Established Phases of Polycystic Kidney Disease

    PubMed Central

    Ta, Michelle H. T.; Schwensen, Kristina G.; Foster, Sheryl; Korgaonkar, Mayuresh; Ozimek-Kulik, Justyna E.; Phillips, Jacqueline K.; Peduto, Anthony; Rangan, Gopala K.

    2016-01-01

    The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs. PMID:27723777

  3. Cerebral oxygen metabolism in patients with early Parkinson's disease.

    PubMed

    Borghammer, Per; Cumming, Paul; Østergaard, Karen; Gjedde, Albert; Rodell, Anders; Bailey, Christopher J; Vafaee, Manoucher S

    2012-02-15

    Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO(2)). To test this hypothesis, we compared CMRO(2) and cerebral blood flow (CBF) PET scans from PD patients and healthy controls. Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO(2) and CBF. Between-group differences were evaluated for absolute data and intensity-normalized values. No group differences were detected in regional magnitudes of CMRO(2) or CBF. Upon normalization using the reference cluster method, significant relative CMRO(2) decreases were evident in widespread prefrontal, parieto-occipital, and lateral temporal regions. Sensory-motor and subcortical regions, brainstem, and the cerebellum were spared. A similar pattern was evident in normalized CBF data, as described previously. While the data did not reveal substantially altered absolute CMRO(2) in brain of PD patients, employing data-driven intensity normalization revealed widespread relative CMRO(2) decreases in cerebral cortex. The detected pattern was very similar to that reported in earlier CBF and CMRglc studies of PD, and in the CBF images from the same subjects. Thus, the present results are consistent with the occurrence of parallel declines in CMRO(2), CBF, and CMRglc in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.

    PubMed

    Mendez, Mario F

    2012-11-01

    Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ∼4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein Eɛ4 (APOE ɛ4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

  5. Volunteering for early phase gene transfer research in Parkinson disease.

    PubMed

    Kim, S Y H; Holloway, R G; Frank, S; Beck, C A; Zimmerman, C; Wilson, R; Kieburtz, K

    2006-04-11

    For early phase trials of novel interventions-such as gene transfer for Parkinson disease (PD)--whose focus is primarily on safety and tolerability, it is important that participants have a realistic understanding of the goals of such research. Recently, some have expressed concern that patients with PD may have unrealistic expectations. The authors examined why patients with PD might volunteer for invasive early phase research by interviewing 92 patients with PD and comparing those who would (n = 46) and those who would not (n = 46) participate in a hypothetical phase I gene-transfer study. The two groups' demographic, clinical, functional, and quality of life measures, as well as their understanding of the research protocol, were similar. The groups did not differ on their perception of potential for personal benefit nor on the level of likelihood of benefit they saw as a precondition for volunteering. However, those willing to participate tended to perceive lower probability of risk, were tolerant of greater probability of risk, and were more optimistic about the phase I study's potential benefits to society. They also appeared more decisive and action-oriented than the unwilling group. It is likely that the decision whether to participate in early phase PD gene transfer studies will depend mostly on patients' attitudes regarding risk, optimism about science, and an action orientation, rather than on their clinical, functional, or demographic characteristics.

  6. Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lehericy, S.; Baulac, M.; Chiras, J.

    1994-05-01

    To evaluate the accuracy of hippocampal and amygdala volume measurements in diagnosing patients in the early stages of Alzheimer disease. Measurements of the hippocampal formation, amygdala, amygdalohippocampal complex (the two measurements summed), caudate nucleus, and ventricles, normalized for total intracranial volume, were obtained on coronal sections (1.5 T, 400/13 [repetition time/echo time], 5 mm) of 13 patients in the mild (minimental status {ge} 21) and five patients in the moderate stages of Alzheimer disease (10 < minimental status < 21), and eight age-matched control subjects. For patients with a minimental status score of 21 or greater, atrophy was significant formore » the amygdala and hippocampal formation (-36% and -25% for amygdala/total intracranial volume and hippocampal formation/total intracranial volume, respectively), but not for the caudate nucleus. No significant ventricular enlargement was found. For patients with a minimental status score less than 21, atrophy was more severe in all structures studied (amygdala/total intracranial volume -40%; hippocampal formation/total intracranial volume, -45%; caudate nucleus/total intracranial volume, -21%), and ventricles were enlarged (63%). No overlap was found between Alzheimer disease and control values for the amygdalohippocampal volume, even in the mild stages of the disease. In Alzheimer disease patients, hippocampal formation volumes correlated with the minimental status. Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease. 46 refs., 8 figs., 2 tabs.« less

  7. Disease activity decrease is associated with improvement in work productivity over 1 year in early axial spondyloarthritis (SPondyloArthritis Caught Early cohort).

    PubMed

    van Lunteren, Miranda; Ez-Zaitouni, Zineb; Fongen, Camilla; Landewé, Robert; Ramonda, Roberta; van der Heijde, Désirée; van Gaalen, Floris A

    2017-12-01

    To assess if a change in disease activity is associated with a change in work productivity loss (WPL) over 1 year in early axial SpA (axSpA) patients. Baseline and 1 year data of axSpA patients in the SPondyloArthritis Caught Early cohort were analysed. Linear regression models were built explaining the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS) over time by the change in absenteeism, presenteeism, WPL and activity impairment over time. Effect modification and confounding were tested for age, gender, arm of Assessment of SpondyloArthritis international Society classification criteria, HLA-B27, duration of chronic back pain, profession and medication. At baseline, in 105 axSpA patients (48% female, mean age 30.8 years, mean symptom duration 13.6 months, 92% HLA-B27 positive, 24% radiographic sacroiliitis), the mean ASDAS was 2.4 (s.d. 1.0), absenteeism 9% (s.d. 23), presenteeism 33% (s.d. 28), WPL 36% (s.d. 30) and activity impairment 37% (s.d. 25). After 1 year, the mean ASDAS decreased to 2.0 (s.d. 0.8) and absenteeism, presenteeism, WPL and activity impairment improved to 6% (s.d. 22), 26% (s.d. 26), 27% (s.d. 29) and 27% (s.d. 26), respectively. Models showed that if ASDAS decreased 1 unit, absenteeism, presenteeism, WPL and activity impairment improved by 5, 17, 16 and 18%, respectively. The impact of disease activity on work productivity was higher in patients with shorter symptom duration and the impact on absenteeism was higher in patients starting pharmacological treatment. In early axSpA patients, work productivity and daily activities are seriously impacted at baseline and 1 year. However, decreasing disease activity is associated with marked improvements in work productivity and daily activities. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Similarities and differences between infantile and early childhood onset vanishing white matter disease.

    PubMed

    Zhou, Ling; Zhang, Haihua; Chen, Na; Zhang, Zhongbin; Liu, Ming; Dai, Lifang; Wang, Jingmin; Jiang, Yuwu; Wu, Ye

    2018-06-01

    Vanishing white matter disease (VWM) is one of the most prevalent inherited leukoencephalopathies in childhood. Infantile VWM is more severe but less understood than the classic early childhood type. We performed a follow-up study on 14 infantile and 26 childhood patients to delineate the natural history and neuroimaging features of VWM. Infantile and childhood patients shared similarities in the incidence of epileptic seizure (35.7 vs. 38.5%) and episodic aggravation (92.9 vs. 84.6%). Developmental delay before disease onset was more common in infantile patients. Motor disability was earlier and more severe in infantile VWM. In survivors with disease durations of 1-3 years, the Gross Motor Function Classification System (GMFCS) was classified as IV-V in 66.7% of infantile and only 29.4% of childhood patients. Kaplan-Meier survival curve analysis indicated that the 5-year survival rates were 21.6 and 91.3% in infantile and childhood VWM, respectively. In terms of MRI, infantile patients showed more extensive involvement and earlier rarefaction, with more common involvement of subcortical white matter, internal capsule, brain stem and dentate nuclei of the cerebellum. Restricted diffusion was more diffuse or extensive in infantile patients. In addition, four novel mutations were identified. In conclusion, we identified some similarities and differences in the natural history and neuroimaging features between infantile and early childhood VWM.

  9. Magnetic resonance imaging and magnetic resonance spectroscopy for detection of early Alzheimer's disease.

    PubMed

    Westman, Eric; Wahlund, Lars-Olof; Foy, Catherine; Poppe, Michaela; Cooper, Allison; Murphy, Declan; Spenger, Christian; Lovestone, Simon; Simmons, Andrew

    2011-01-01

    Alzheimer's disease is the most common form of neurodegenerative disorder and early detection is of great importance if new therapies are to be effectively administered. We have investigated whether the discrimination between early Alzheimer's disease (AD) and elderly healthy control subjects can be improved by adding magnetic resonance spectroscopy (MRS) measures to magnetic resonance imaging (MRI) measures. In this study 30 AD patients and 36 control subjects were included. High resolution T1-weighted axial magnetic resonance images were obtained from each subject. Automated regional volume segmentation and cortical thickness measures were determined for the images. 1H MRS was acquired from the hippocampus and LCModel was used for metabolic quantification. Altogether, this yielded 58 different volumetric, cortical thickness and metabolite ratio variables which were used for multivariate analysis to distinguish between subjects with AD and Healthy controls. Combining MRI and MRS measures resulted in a sensitivity of 97% and a specificity of 94% compared to using MRI or MRS measures alone (sensitivity: 87%, 76%, specificity: 86%, 83% respectively). Adding the MRS measures to the MRI measures more than doubled the positive likelihood ratio from 6 to 17. Adding MRS measures to a multivariate analysis of MRI measures resulted in significantly better classification than using MRI measures alone. The method shows strong potential for discriminating between Alzheimer's disease and controls.

  10. Protective role of biosynthesized silver nanoparticles against early blight disease in Solanum lycopersicum.

    PubMed

    Kumari, Madhuree; Pandey, Shipra; Bhattacharya, Arpita; Mishra, Aradhana; Nautiyal, C S

    2017-12-01

    Tomato suffers a huge loss every year because of early blight disease. This study focuses on efficient inhibition of Alternaria solani, the causative agent of early blight disease in tomato in vitro and in vivo. Foliar spray of 5 μg/mL of biosynthesized silver nanoparticles in A. solani infected plants resulted in significant increase of 32.58% in fresh weight and 23.52% in total chlorophyll content of tomato as compared to A. solani infected plants. A decrease of 48.57, 30, 39.59 and 28.57% was observed in fungal spore count, lipid peroxidation, proline content and superoxide dismutase respectively in infected tomato plants after treatment with synthesized silver nanoparticles as compared to A. solani infected plants. No significant variation in terms of soil pH, cultured population, carbon source utilization pattern and soil enzymes including dehydrogenase, urease, protenase and β-glucosidase was observed after foliar spray of nanoparticles. It was revealed that direct killing of pathogens, increased photosynthetic efficiencies, increased plant resistance and decrease in stress parameters and stress enzymes are the mechanisms employed by plants and nanoparticles simultaneously to combat the biotic stress. Biosynthesized silver nanoparticles bear the potential to revolutionize plant disease management, though the molecular aspects of increased resistance must be looked upon. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Completed suicide in an autopsy-confirmed case of early onset Alzheimer's disease.

    PubMed

    Hartzell, Jennifer Wiener; Geary, Richard; Gyure, Kymberly; Chivukula, Venkata Ravi; Haut, Marc W

    2018-04-01

    We report a case of a 57-year-old male with clinically diagnosed and autopsy-confirmed early onset Alzheimer's disease who completed suicide by gunshot wound to the chest. This case has several unique aspects that have not been discussed in previous case reports of completed suicide in Alzheimer's disease. In particular, our patient's death was highly planned with successful compensation for his cognitive deficits. After all firearms had been removed from the home as a safety precaution, he obtained a new weapon, hid it and left himself cues to find and use it. The case is discussed in the context of literature differentiating the neural circuitry propagating impulsive versus planned suicidal acts.

  12. Quantitative structural MRI for early detection of Alzheimer’s disease

    PubMed Central

    McEvoy, Linda K; Brewer, James B

    2011-01-01

    Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder that is not currently diagnosed until a patient reaches the stage of dementia. There is a pressing need to identify AD at an earlier stage, so that treatment, when available, can begin early. Quantitative structural MRI is sensitive to the neurodegeneration that occurs in mild and preclinical AD, and is predictive of decline to dementia in individuals with mild cognitive impairment. Objective evidence of ongoing brain atrophy will be critical for risk/benefit decisions once potentially aggressive, disease-modifying treatments become available. Recent advances have paved the way for the use of quantitative structural MRI in clinical practice, and initial clinical use has been promising. However, further experience with these measures in the relatively unselected patient populations seen in clinical practice is needed to complete translation of the recent enormous advances in scientific knowledge of AD into the clinical realm. PMID:20977326

  13. Motion-based video monitoring for early detection of livestock diseases: The case of African swine fever

    PubMed Central

    Martínez-Avilés, Marta; Ivorra, Benjamin; Martínez-López, Beatriz; Ramos, Ángel Manuel; Sánchez-Vizcaíno, José Manuel

    2017-01-01

    Early detection of infectious diseases can substantially reduce the health and economic impacts on livestock production. Here we describe a system for monitoring animal activity based on video and data processing techniques, in order to detect slowdown and weakening due to infection with African swine fever (ASF), one of the most significant threats to the pig industry. The system classifies and quantifies motion-based animal behaviour and daily activity in video sequences, allowing automated and non-intrusive surveillance in real-time. The aim of this system is to evaluate significant changes in animals’ motion after being experimentally infected with ASF virus. Indeed, pig mobility declined progressively and fell significantly below pre-infection levels starting at four days after infection at a confidence level of 95%. Furthermore, daily motion decreased in infected animals by approximately 10% before the detection of the disease by clinical signs. These results show the promise of video processing techniques for real-time early detection of livestock infectious diseases. PMID:28877181

  14. Cystic fibrosis in young children: A review of disease manifestation, progression, and response to early treatment.

    PubMed

    VanDevanter, Donald R; Kahle, Jennifer S; O'Sullivan, Amy K; Sikirica, Slaven; Hodgkins, Paul S

    2016-03-01

    Studies have described illness associated with cystic fibrosis (CF) early in life, but there is no comprehensive accounting of the prevalence and ages of disease manifestation and progression described in individual studies. We searched for peer-reviewed English-language studies of the health of children ≤6years old with CF (published 1990-2014). Structural abnormalities and dysfunction of the digestive and respiratory systems were summarized across relevant studies by system and age group. Primary studies (125 total) from 22 countries described abnormalities, dysfunction, and disease progression in infancy and early childhood. Improved health was consistently observed in association with diagnosis via newborn screening compared with cohorts diagnosed later by symptomatic presentation. The peer-reviewed literature is remarkably consistent: CF-associated growth impairment and airway abnormalities are reported at birth, and disease progression is reported in infancy and throughout childhood. Earlier access to routine CF management is associated with improved subsequent health status. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

    PubMed

    Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

    2017-11-09

    Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

  16. Early detection of emerging zoonotic diseases with animal morbidity and mortality monitoring.

    PubMed

    Bisson, Isabelle-Anne; Ssebide, Benard J; Marra, Peter P

    2015-03-01

    Diseases transmitted between animals and people have made up more than 50% of emerging infectious diseases in humans over the last 60 years and have continued to arise in recent months. Yet, public health and animal disease surveillance programs continue to operate independently. Here, we assessed whether recent emerging zoonotic pathogens (n = 143) are known to cause morbidity or mortality in their animal host and if so, whether they were first detected with an animal morbidity/mortality event. We show that although sick or dead animals are often associated with these pathogens (52%), only 9% were first detected from an animal morbidity or mortality event prior to or concurrent with signs of illness in humans. We propose that an animal morbidity and mortality reporting program will improve detection and should be an essential component of early warning systems for zoonotic diseases. With the use of widespread low-cost technology, such a program could engage both the public and professionals and be easily tested and further incorporated as part of surveillance efforts by public health officials.

  17. Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

    PubMed

    Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

    2012-01-01

    Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

  18. Diet Quality throughout Early Life in Relation to Allergic Sensitization and Atopic Diseases in Childhood.

    PubMed

    Nguyen, Anh N; Elbert, Niels J; Pasmans, Suzanne G M A; Kiefte-de Jong, Jessica C; de Jong, Nicolette W; Moll, Henriëtte A; Jaddoe, Vincent W V; de Jongste, Johan C; Franco, Oscar H; Duijts, Liesbeth; Voortman, Trudy

    2017-08-05

    Early-life nutrition is an important modifiable determinant in the development of a child's immune system, and may thereby influence the risk of allergic sensitization and atopic diseases. However, associations between overall dietary patterns and atopic diseases in childhood remain unclear. We examined associations of diet quality in early life with allergic sensitization, self-reported physician-diagnosed inhalant and food allergies, eczema, and asthma among 5225 children participating in a population-based cohort in the Netherlands. Diet was assessed during pregnancy, infancy, and childhood using validated food-frequency questionnaires. We calculated food-based diet quality scores (0-10 or 0-15), reflecting adherence to dietary guidelines. At age 10 years, allergic sensitization was assessed with skin prick tests. Information on physician-diagnosed inhalant and food allergies, eczema, and asthma was obtained with questionnaires. We observed no associations between diet quality during pregnancy and allergic sensitization (odds ratio (OR) = 1.05 per point in the diet score, 95% confidence interval (CI): 0.99, 1.13), allergies (0.96, 95% CI: 0.88, 1.04), eczema (0.99, 95% CI: 0.93, 1.06), or asthma (0.93, 95% CI: 0.85, 1.03) in childhood. Also, diet quality in infancy or childhood were not associated with atopic outcomes in childhood. Our findings do not support our hypothesis that a healthy dietary pattern in early life is associated with a lower risk of allergic sensitization or atopic diseases in childhood.

  19. Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease.

    PubMed

    Kelsen, Judith R; Baldassano, Robert N; Artis, David; Sonnenberg, Gregory F

    2015-09-01

    Inflammatory bowel disease (IBD) is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD occurring before the age of 5 represent a unique form of disease, termed Very Early Onset (VEO)-IBD, which is phenotypically- and genetically-distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies, and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal disease. Here we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation.

  20. Exposure Assessment Tools by Lifestages and Populations - Lifestages

    EPA Pesticide Factsheets

    EPA ExpoBox is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

  1. Predictors of driving safety in early Alzheimer disease.

    PubMed

    Dawson, J D; Anderson, S W; Uc, E Y; Dastrup, E; Rizzo, M

    2009-02-10

    To measure the association of cognition, visual perception, and motor function with driving safety in Alzheimer disease (AD). Forty drivers with probable early AD (mean Mini-Mental State Examination score 26.5) and 115 elderly drivers without neurologic disease underwent a battery of cognitive, visual, and motor tests, and drove a standardized 35-mile route in urban and rural settings in an instrumented vehicle. A composite cognitive score (COGSTAT) was calculated for each subject based on eight neuropsychological tests. Driving safety errors were noted and classified by a driving expert based on video review. Drivers with AD committed an average of 42.0 safety errors/drive (SD = 12.8), compared to an average of 33.2 (SD = 12.2) for drivers without AD (p < 0.0001); the most common errors were lane violations. Increased age was predictive of errors, with a mean of 2.3 more errors per drive observed for each 5-year age increment. After adjustment for age and gender, COGSTAT was a significant predictor of safety errors in subjects with AD, with a 4.1 increase in safety errors observed for a 1 SD decrease in cognitive function. Significant increases in safety errors were also found in subjects with AD with poorer scores on Benton Visual Retention Test, Complex Figure Test-Copy, Trail Making Subtest-A, and the Functional Reach Test. Drivers with Alzheimer disease (AD) exhibit a range of performance on tests of cognition, vision, and motor skills. Since these tests provide additional predictive value of driving performance beyond diagnosis alone, clinicians may use these tests to help predict whether a patient with AD can safely operate a motor vehicle.

  2. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

    PubMed

    Hacker, Mallory L; DeLong, Mahlon R; Turchan, Maxim; Heusinkveld, Lauren E; Ostrem, Jill L; Molinari, Anna L; Currie, Amanda D; Konrad, Peter E; Davis, Thomas L; Phibbs, Fenna T; Hedera, Peter; Cannard, Kevin R; Drye, Lea T; Sternberg, Alice L; Shade, David M; Tonascia, James; Charles, David

    2018-06-29

    To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT ( p = 0.001). These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor. © 2018 American Academy of Neurology.

  3. Driving in Early-Stage Alzheimer's Disease: An Integrative Review of the Literature.

    PubMed

    Davis, Rebecca L; Ohman, Jennifer M

    2017-03-01

    One of the most difficult decisions for individuals with Alzheimer's disease (AD) is when to stop driving. Because driving is a fundamental activity linked to socialization, independent functioning, and well-being, making the decision to stop driving is not easy. Cognitive decline in older adults can lead to getting lost while driving, difficulty detecting and avoiding hazards, as well as increased errors while driving due to compromised judgment and difficulty in making decisions. The purpose of the current literature review was to synthesize evidence regarding how individuals with early-stage AD, their families, and providers make determinations about driving safety, interventions to increase driving safety, and methods to assist cessation and coping for individuals with early-stage AD. The evidence shows that changes in driving ability start early and progress throughout the trajectory of AD. Some individuals with mild cognitive impairment or early-stage AD may be safe to drive for a period of time. Support groups aimed at helping with the transition have been shown to be helpful for individuals who stop driving. Research and practice must support interventions to help individuals maintain safety while driving, as well as cope with driving cessation. [Res Gerontol Nurs. 2017; 10(2):86-100.]. Copyright 2016, SLACK Incorporated.

  4. Determinants of Objectively Measured Physical Functional Performance in Early to Mid-stage Parkinson Disease

    PubMed Central

    Kluger, Benzi M.; Brown, R. Preston; Aerts, Shanae; Schenkman, Margaret

    2014-01-01

    Background Parkinson disease (PD) may lead to functional limitations through both motor and non-motor symptoms. While patients with advanced disease have well-documented and profound functional limitations, less is known about the determinants of function in early to mid-stage disease where interventions may be more likely to benefit and preserve function. Objective The objective of the current study was to identify motor, cognitive and gait determinants of physical functional performance in patients with early to mid-stage PD. Design Secondary analysis of cross-sectional baseline data from a randomized clinical trial of exercise. Setting Tertiary academic medical center. Participants 121 patients with early to mid-stage PD. Methods Our functional performance outcomes included: 1) the Continuous Scale Functional Performance Test (CS-PFP; primary outcome); 2) the timed up and go (TUG) tests; and Section 2 (Activities of Daily Living) of the Unified Parkinson's Disease Rating Scale (UPDRS). Explanatory variables included measures of disease severity, motor function, cognitive function, balance and gait. Step-wise linear regression models were used to determine correlations between explanatory variables and outcome measures. Results In our regression models the CS-PFP significantly correlated with walking endurance (six minute walk; r2 = 0.12, p < .0001), turning ability (360 degree turn; r2 = .03, p = .002), attention (brief test of attention; r2 = .01, p = .03), overall cognitive status (Mini-mental State Examination; r2 = .01, p = .04) and bradykinesia (timed tapping; r2 = .02, p = .02). The TUG significantly correlated with walking speed (5 meter walk; r2 = 0.33, p <.0001), stride length (r2 = 0.25, p <.0001), turning ability (360 turn r2 = .05, p = .0003) and attention (r2 = .016, p = .03). Section 2 of the UPDRS was significantly correlated with endurance (r2 = .09, p < .0001), turning ability (r2 = .03, p = .001) and attention (r2 = .01, p = .03). Conclusions

  5. Early Parkinson's disease patients on rasagiline present with better odor discrimination.

    PubMed

    Haehner, Antje; Habersack, Angela; Wienecke, Miriam; Storch, Alexander; Reichmann, Heinz; Hummel, Thomas

    2015-11-01

    The effects of rasagiline on olfaction in animal studies are convincing. However, apart from various anecdotal patient reports, they could not be reproduced in prospective studies in humans. Cross-sectional data of large patient groups are still missing. The aim of this study was therefore to determine the olfactory function in a broad heterogeneous Parkinson's disease (PD) population with and without rasagiline intake. In this single-center, cross-sectional study 224 PD patients with and without rasagiline (1 mg/day) participated. Seventy-four of them received rasagiline as mono, or adjunct therapy. One-hundred fifty patients were untreated or received PD medication other than rasagiline. Comprehensive olfactory testing was performed for phenyl-ethyl alcohol odor thresholds, odor discrimination, and odor identification. Olfactory function did not differ between the two treatment groups with disease duration up to 29 years. Rasagiline-treated patients with disease duration of less than 8 years, however, presented with significant better odor discrimination abilities compared to PD patients without rasagiline treatment. This effect was no longer evident in patients with longer disease duration and proofed to be independent of age, sex, and medication. Our results may suggest that rasagiline treatment has a positive effect on the processing of olfactory information in early PD.

  6. Early, structured disease modifying anti-rheumatic drug (DMARD) therapy reduces cardiovascular risk in rheumatoid arthritis--a single centre study using non-biologic drugs.

    PubMed

    Chatterjee, Sumit; Sarkate, Pankaj; Ghosh, Sudip; Biswas, Monodeep; Ghosh, Alakendu

    2013-08-01

    Rheumatoid arthritis, being a chronic disease requires long-term management of patients with drugs. The increasing cost of biologics in this era of disease management led us to devise a treatment regime, optimal for use in a developing country like India, which was economical as well as effective in controlling disease activity. To investigate if combination therapy with DMARDs can reduce cardiovascular risk in early Rheumatoid Arthritis, besides controlling disease activity. A small cohort of early Rheumatoid subjects with disease duration less than 1 year were treated with a structured DMARD regime and were followed up over a year. Disease activity score, C-reactive protein (CRP) and cardiac risk markers like lipid panel and carotid intima-medial thickness were monitored at 6 months and 1 year. A significant reduction (p < 0.001) of disease activity as well as cardiac risk parameters were observed. Our study showed that treatment of early rheumatoid arthritis with a combination regime of traditional DMARDs is highly effective in controlling disease activity as well as cardiovascular risk.

  7. Early onset of bilateral brachial plexopathy during mantle radiotherapy for Hodgkin's disease.

    PubMed

    Churn, M; Clough, V; Slater, A

    2000-01-01

    We report a case of brachial plexus neuropathy occurring in a 50-year-old man treated with standard mantle radiotherapy for early-stage Hodgkin's disease. A dose of 35 Gy in 20 fractions was given to the mantle field, following by a boost to the right side of the neck (8 Gy in four fractions). The onset of symptoms was early in the course of treatment and a gradual and almost full recovery was observed over 3 years after completion ofradiotherapy. The diagnosis was supported by electromyography. The temporal relationship of the radiotherapy and the onset of the brachial plexus neuropathy suggests a cause and effect, but this association is rarely reported after mantle radiotherapy. We review the aetiology of this condition and postulate possible mechanisms in this patient.

  8. Network for Early Onset Cystic Kidney Diseases-A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood.

    PubMed

    König, Jens Christian; Titieni, Andrea; Konrad, Martin

    2018-01-01

    Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet-Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype-phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases. To tackle these challenges comprehensive scientific approaches are urgently needed that match the ongoing "revolution" in genetics and molecular biology with an improved efficacy of clinical data collection. Network for early onset cystic kidney diseases (NEOCYST) is a multidisciplinary, multicenter collaborative combining a detailed collection of clinical data with translational scientific approaches addressing the genetic, molecular, and functional background of hereditary cystic kidney diseases. Consisting of seven work packages, including an international registry as well as a biobank, NEOCYST is not only dedicated to current scientific questions, but also provides a platform for longitudinal clinical surveillance and provides precious sources for high-quality research projects and future clinical trials. Funded by the German Federal Government, the NEOCYST collaborative started in February 2016. Here, we would like to introduce the rationale, design, and objectives of the network followed by a short overview on the current state of progress.

  9. Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis.

    PubMed

    Finckh, Axel; Bansback, Nick; Marra, Carlo A; Anis, Aslam H; Michaud, Kaleb; Lubin, Stanley; White, Marc; Sizto, Sonia; Liang, Matthew H

    2009-11-03

    Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. Decision analytic model with probabilistic sensitivity analyses. Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. U.S. adults with very early RA (symptom duration disease-modifying antirheumatic drugs (DMARDs) at 1 year for nonresponders; early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate. Cost per quality-adjusted life-year (QALY) gained. By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater. The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for

  10. Early diagnosis of Alzheimer's disease and Parkinson's disease associated with dementia using cerebral perfusion SPECT.

    PubMed

    Song, In-Uk; Chung, Yong-An; Chung, Sung-Woo; Jeong, Jaeseung

    2014-01-01

    Since patterns of cognitive dysfunction in mild Parkinson's disease associated with dementia (PDD) are similar to those in mild Alzheimer's disease (AD), it is difficult to accurately differentiate between these two types of dementia in their early phases using neuropsychological tests. The purpose of the current study was to investigate differences in cerebral perfusion patterns of patients with AD and PDD at the earliest stages using single photon emission computed tomography (SPECT). We consecutively recruited 31 patients with mild PDD, 32 patients with mild probable AD and 33 age-matched healthy subjects. All subjects underwent (99m)Tc-hexamethylpropyleneamine oxime perfusion SPECT and completed general neuropsychological tests. We found that both mild PDD and AD patients showed distinct hypoperfusion in frontal, parietal and temporal regions, compared with healthy subjects. More importantly, hypoperfusion in occipital and cerebellar regions was observed only in mild PDD. The observation of a significant decrease in cerebral perfusion in occipital and cerebellar regions in patients with mild PDD is likely useful to differentiate between PDD and AD at the earliest stages. © 2013 S. Karger AG, Basel.

  11. The Cognitive and Neural Expression of Semantic Memory Impairment in Mild Cognitive Impairment and Early Alzheimer's Disease

    ERIC Educational Resources Information Center

    Joubert, Sven; Brambati, Simona M.; Ansado, Jennyfer; Barbeau, Emmanuel J.; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Celine; Kergoat, Marie-Jeanne

    2010-01-01

    Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to…

  12. Souvenaid®: a new approach to management of early Alzheimer's disease.

    PubMed

    Ritchie, C W; Bajwa, J; Coleman, G; Hope, K; Jones, R W; Lawton, M; Marven, M; Passmore, P

    2014-03-01

    Synaptic loss correlates closely with cognitive deficits in Alzheimer's disease and represents a new target for intervention. Souvenaid® is the first medical nutrition product to be designed to support synapse formation and function in early Alzheimer's disease, and has undergone an extensive, 12-year development programme. The relatively large amount of clinical data available for Souvenaid® is unusual for a medical nutrition product. Souvenaid® contains omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid), uridine (as uridine monophosphate) and choline which are nutritional precursors required for synaptic membrane phospholipid synthesis, together with phospholipids and other cofactors. Souvenaid® has demonstrated cognitive benefits in patients with mild Alzheimer's disease but not in patients with mild-to-moderate Alzheimer's disease. Two randomised, double-blind, controlled trials (duration 12 and 24 weeks) in patients with mild Alzheimer's disease untreated with acetylcholinesterase inhibitors and/or memantine have demonstrated that Souvenaid® is well tolerated and improves episodic memory performance. The daily intake of Souvenaid® has not been associated with any harmful effects or interactions with medications and none are anticipated. The ongoing, 24-month, European Union-funded LipiDiDiet trial in subjects with prodromal Alzheimer's disease is evaluating the potential benefits of Souvenaid® on memory and in slowing progression to Alzheimer's dementia. If Souvenaid® induces synaptogenesis and improved synaptic function, it may provide benefits in other clinical conditions characterised by neurodegeneration. A number of trials are ongoing and planned to evaluate the potential wider benefits of Souvenaid®.

  13. Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

    PubMed

    Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

    2017-02-01

    Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

    PubMed Central

    Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

    2014-01-01

    Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

  15. Early detection of foot-and-mouth disease virus from infected cattle using a dry filter air sampling system

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid outbreak control. Air sampling collection has been demonstrated as a useful technique for detection of FMDV RNA in infected animals, related to ...

  16. Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions

    PubMed Central

    Loranger, Hannah; Zotz, Gerhard; Bader, Maaike Y.

    2016-01-01

    On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia. In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics. PMID:27402618

  17. Early postoperative physical therapy for improving short-term gross motor outcome in infants with cyanotic and acyanotic congenital heart disease.

    PubMed

    Haseba, Sumihito; Sakakima, Harutoshi; Nakao, Syuhei; Ohira, Misaki; Yanagi, Shigefumi; Imoto, Yutaka; Yoshida, Akira; Shimodozono, Megumi

    2018-07-01

    We analysed the gross motor recovery of infants and toddlers with cyanotic and acyanotic congenital heart disease (CHD) who received early postoperative physical therapy to see whether there was any difference in the duration to recovery. This study retrospectively evaluated the influence of early physical therapy on postoperative gross motor outcomes of patients with CHD. The gross motor ability of patients with cyanotic (n = 25, average age: 376.4 days) and acyanotic (n = 26, average age: 164.5 days) CHD was evaluated using our newly developed nine-grade mobility assessment scale. Physical therapy was started at an average of five days after surgery, during which each patient's gross motor ability was significantly decreased compared with the preoperative level. Patients (who received early postoperative physical therapy) with cyanotic (88.0%) and acyanotic CHD (96.2%) showed improved preoperative mobility grades by the time of hospital discharge. However, patients with cyanotic CHD had a significantly prolonged recovery period compared to those with acyanotic CHD (p < .01). The postoperative recovery period to preoperative mobility grade was significantly correlated with pre-, intra-, and postoperative factors. Our findings suggested that infants with cyanotic CHD are likely at a greater risk of gross motor delays, the recovery of which might differ between infants with cyanotic and acyanotic CHD after cardiac surgery. Early postoperative physical therapy promotes gross motor recovery. Implications of Rehabilitation Infants and toddlers with cyanotic congenital heart disease are likely at greater risk of gross motor delays and have a prolonged recovery period of gross motor ability compared to those with acyanotic congenital heart disease. Early postoperative physical therapy for patients with congenital heart disease after cardiac surgery promoted gross motor recovery. The postoperative recovery period to preoperative mobility grade was affected

  18. Prenatal exposure to bisphenol A and risk of allergic diseases in early life.

    PubMed

    Zhou, Aifen; Chang, Huailong; Huo, Wenqian; Zhang, Bin; Hu, Jie; Xia, Wei; Chen, Zhong; Xiong, Chao; Zhang, Yaqi; Wang, Youjie; Xu, Shunqing; Li, Yuanyuan

    2017-06-01

    Prenatal exposure to bisphenol A (BPA) affects immune system and promotes allergy and asthma in mice, but findings in human studies are limited. We investigated whether prenatal exposure to BPA is associated with increased risk of allergic diseases in infants. We measured BPA concentrations in maternal urine samples collected at delivery from 412 women in Wuhan, China. The occurrence of allergic diseases including eczema and wheeze were assessed at age 6 mo through questionnaires. We used logistic regression to evaluate the association between urinary BPA levels and the risk of allergic diseases. Mothers of infants with allergic diseases had significantly higher urinary BPA levels than those of infants without allergic diseases (median: 2.35 vs. 4.55 µg/l, P = 0.03). Increased risk of infant allergic diseases was associated with creatinine-adjusted maternal urinary BPA concentrations. And this association was limited to females (odds ratio (OR) = 1.36; 95% confidence interval (CI): 1.10-1.79) rather than males. After stratification by maternal age, the association was only significant in infants of mothers who were younger than 25 y old (OR = 1.90; 95% CI: 1.09-3.29). Prenatal exposure to BPA may potentially increase the risk of allergic diseases at very early life in female infants.

  19. (99m)Tc-MDP SPECT/CT as the one-stop imaging modality for the diagnosis of early setting of Kienbock's disease.

    PubMed

    Arora, S; Singh Dhull, V; Karunanithi, S; Kumar Parida, G; Sharma, A; Shamim, S A

    2015-01-01

    (99m)Tc-Methylene diphosphonate (MDP) triple phase bone scintigraphy (BS) has a role in early diagnosis of Kienbock's disease, especially when the X-ray is negative. Early diagnosis can result in prompt management of the patient since wrist pain in older individuals due to aging may go unnoticed or be due to other diagnoses with the production of greater damage and eventually a worse prognosis. Herein, we present a case report of a 29-year-old female with Kienbock's disease in whom the X-ray was negative and MRI incorrect. The (99m)Tc-MDP SPECT/CT BS helped the diagnosis of the disease in an early stage (stage 1) and had a clinical impact on the patient's management. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  20. Regeneration of different plant functional types in a Masson pine forest following pine wilt disease.

    PubMed

    Hu, Guang; Xu, Xuehong; Wang, Yuling; Lu, Gao; Feeley, Kenneth J; Yu, Mingjian

    2012-01-01

    Pine wilt disease is a severe threat to the native pine forests in East Asia. Understanding the natural regeneration of the forests disturbed by pine wilt disease is thus critical for the conservation of biodiversity in this realm. We studied the dynamics of composition and structure within different plant functional types (PFTs) in Masson pine forests affected by pine wilt disease (PWD). Based on plant traits, all species were assigned to four PFTs: evergreen woody species (PFT1), deciduous woody species (PFT2), herbs (PFT3), and ferns (PFT4). We analyzed the changes in these PFTs during the initial disturbance period and during post-disturbance regeneration. The species richness, abundance and basal area, as well as life-stage structure of the PFTs changed differently after pine wilt disease. The direction of plant community regeneration depended on the differential response of the PFTs. PFT1, which has a higher tolerance to disturbances, became dominant during the post-disturbance regeneration, and a young evergreen-broad-leaved forest developed quickly after PWD. Results also indicated that the impacts of PWD were dampened by the feedbacks between PFTs and the microclimate, in which PFT4 played an important ecological role. In conclusion, we propose management at the functional type level instead of at the population level as a promising approach in ecological restoration and biodiversity conservation.

  1. Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

    PubMed

    Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

    2010-05-01

    Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

  2. Independent Deficits of Visual Word and Motion Processing in Aging and Early Alzheimer's Disease

    PubMed Central

    Velarde, Carla; Perelstein, Elizabeth; Ressmann, Wendy; Duffy, Charles J.

    2013-01-01

    We tested whether visual processing impairments in aging and Alzheimer's disease (AD) reflect uniform posterior cortical decline, or independent disorders of visual processing for reading and navigation. Young and older normal controls were compared to early AD patients using psychophysical measures of visual word and motion processing. We find elevated perceptual thresholds for letters and word discrimination from young normal controls, to older normal controls, to early AD patients. Across subject groups, visual motion processing showed a similar pattern of increasing thresholds, with the greatest impact on radial pattern motion perception. Combined analyses show that letter, word, and motion processing impairments are independent of each other. Aging and AD may be accompanied by independent impairments of visual processing for reading and navigation. This suggests separate underlying disorders and highlights the need for comprehensive evaluations to detect early deficits. PMID:22647256

  3. An improved arteriovenous classification method for the early diagnostics of various diseases in retinal image.

    PubMed

    Xu, Xiayu; Ding, Wenxiang; Abràmoff, Michael D; Cao, Ruofan

    2017-04-01

    Retinal artery and vein classification is an important task for the automatic computer-aided diagnosis of various eye diseases and systemic diseases. This paper presents an improved supervised artery and vein classification method in retinal image. Intra-image regularization and inter-subject normalization is applied to reduce the differences in feature space. Novel features, including first-order and second-order texture features, are utilized to capture the discriminating characteristics of arteries and veins. The proposed method was tested on the DRIVE dataset and achieved an overall accuracy of 0.923. This retinal artery and vein classification algorithm serves as a potentially important tool for the early diagnosis of various diseases, including diabetic retinopathy and cardiovascular diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Chronic restraint stress during early Theiler’s virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity

    PubMed Central

    Young, Erin E.; Sieve, Amy N.; Vichaya, Elisabeth G.; Carcoba, Luis M.; Young, Colin R.; Ambrus, Andrew; Storts, Ralph; Welsh, C. Jane R.; Meagher, Mary W.

    2010-01-01

    Theiler’s murine encephalomyelitis virus (TMEV) infection is a well-characterized model of multiple sclerosis (MS). Previous research has shown that chronic restraint stress (RS) during early TMEV infection exacerbates behavioral signs of disease. The present data suggest RS-induced increases in CNS inflammation, demyelination, and axonal degeneration may underlie this exacerbation. In addition, we report that males exhibit greater CNS inflammation and higher numbers of demyelinating lesions while females show greater susceptibility to RS-induced exacerbation. These findings indicate RS during early TMEV infection increases CNS lesion formation during the late phase and suggest the effects of RS are sex-dependent. PMID:20167380

  5. Reduced limbic and hypothalamic volumes correlate with bone density in early Alzheimer's disease.

    PubMed

    Loskutova, Natalia; Honea, Robyn A; Brooks, William M; Burns, Jeffrey M

    2010-01-01

    Accelerated bone loss is associated with Alzheimer's disease (AD). Although the central nervous system plays a direct role in regulating bone mass, primarily through the actions of the hypothalamus, there is little work investigating the possible role of neurodegeneration in bone loss. In this cross-sectional study, we examined the association between bone mineral density (BMD) and neuroimaging markers of neurodegeneration (i.e., global and regional measures of brain volume) in early AD and non-demented aging. Fifty-five non-demented and 63 early AD participants underwent standard neurological and neuropsychological assessment, structural MRI scanning, and dual energy x-ray absorptiometry. In early AD, voxel-based morphometry analyses demonstrated that low BMD was associated with low volume in limbic grey matter (GM) including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional GM volume was found in non-demented controls. The hypothesis-driven region of interest analysis further isolating the hypothalamus demonstrated a positive relationship between BMD and hypothalamic volume after controlling for age and gender in the early AD group but not in non-demented controls. These results demonstrate that lower BMD is associated with lower hypothalamic volume in early AD, suggesting that central mechanisms of bone remodeling may be disrupted by neurodegeneration.

  6. Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

    PubMed

    Murphy, M O; Cohn, D M; Loria, A S

    2017-03-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Biomarkers for early diagnosis of Alzheimer disease: 'ALZheimer ASsociated gene'--a new blood biomarker?

    PubMed

    Jellinger, Kurt A; Janetzky, Bernd; Attems, Johannes; Kienzl, Elisabeth

    2008-08-01

    Simple, non-invasive tests for an early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers (plasma/serum, platelets, urine, connective tissue) for the early diagnosis of Alzheimer disease (AD) are available. In disease stages with evident cognitive disturbances, the clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. Diagnostic sensitivity and specificity even in early disease stages are improved by CSF markers, in particular combined tau and amyloid beta peptides (Abeta) and plasma markers (eg, Abeta-42/Abeta-40 ratio). Recently, a novel gene/protein--ALZAS (Alzheimer Associated Protein)--with a 79 amino acid sequence, containing the amyloid beta-42 fragment (Abeta-42), the amyloid precursor protein (APP) transmembrane signal and a 12 amino acid C-terminal, not present in any other known APP alleles, has been discovered on chromosome 21 within the APP region. Reverse transcriptase-PCR revealed the expression of the transcript of this protein in the cortex and hippocampal regions as well as in lymphocytes of human AD patients. The expression of ALZAS is mirrored by a specific autoimmune response in AD patients, directed against the ct-12 end of the ALZAS-peptide but not against the Abeta-sequence. ELISA studies of plasma detected highest titers of ALZAS in patients with mild cognitive impairment (presymptomatic AD), but only moderately increased titers in autopsy-confirmed AD, whereas low or undetectable ct-12 titers were found in cognitively intact age-matched subjects and young controls. The antigen, ALZAS protein, was detected in plasma in later clinical stages of AD. It is suggested that ALZAS represents an indicator in a dynamic equilibrium between both peripheral and brain degenerative changes in AD and may become a useful "non-invasive" diagnostic marker via a simple blood test.

  8. Chronic Disease Management Strategies of Early Childhood Caries: Support from the Medical and Dental Literature.

    PubMed

    Edelstein, Burton L; Ng, Man Wai

    2015-01-01

    An Institute of Medicine report places chronic disease management (CDM) as an intervention on a treatment spectrum between prevention and acute care. CDM commonly focuses on conditions in which patient self-care efforts are significant. Framing early childhood caries (ECC) as such a chronic condition invites dentistry to reconsider its approach to caries management and shift gears from a strictly surgical approach to one that also incorporates a medical approach. This paper's purpose was to explore the definition of and concepts inherent in CDM. An explanatory model is introduced to describe the multiple factors that influence ECC-CDM strategies. Reviewed literature suggests that early evidence from ECC-CDM interventions, along with results of pediatric asthma and diabetes CDM, supports CDM of ECC as a valid approach that is independent of both prevention and repair. Early results of ECC-CDM endeavors have demonstrated a reduction in rates of new cavitation, dental pain, and referral to the operating room compared to baseline rates. ECC-CDM strategies hold strong promise to curtail caries activity while complementing dental repair when needed, thereby reducing disease progression and cavity recurrence. Institutionalizing ECC-CDM will both require and benefit from evolving health care delivery and financing systems that reward positive health outcomes.

  9. Spatiotemporal proteomic analyses during pancreas cancer progression identifies serine/threonine stress kinase 4 (STK4) as a novel candidate biomarker for early stage disease.

    PubMed

    Mirus, Justin E; Zhang, Yuzheng; Hollingsworth, Michael A; Solan, Joell L; Lampe, Paul D; Hingorani, Sunil R

    2014-12-01

    Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of <5%. Detection of resectable disease improves survival rates, but access to tissue and other biospecimens that could be used to develop early detection markers is confounded by the insidious nature of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing ∼2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach

  10. Sydenham chorea: clinical, EEG, MRI and SPECT findings in the early stage of the disease.

    PubMed

    Heye, N; Jergas, M; Hötzinger, H; Farahati, J; Pöhlau, D; Przuntek, H

    1993-02-01

    An 18-year-old man suffered from acute Sydenham chorea appearing coincidently with beta-haemolytic streptococcal throat infection. Imaging techniques documented lesions of basal ganglia and substantia nigra. In the early course of the disease vascular lesions may be important pathogenetic mechanisms of this acquired movement disorder.

  11. Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis

    PubMed Central

    Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A.; Kern, Volker D.; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T.; Romero, Klaus

    2017-01-01

    Abstract Given the recognition that disease‐modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient‐level longitudinal data of 672 subjects with early‐stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP‐1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed‐effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was –3.16 (90% confidence interval [CI] = –0.96 to –5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. PMID:28749580

  12. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brice, A.; Tardieu, S.; Campion, D.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelicmore » association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.« less

  13. Demons, nature, or God? Witchcraft accusations and the French disease in early modern Venice.

    PubMed

    McGough, Laura J

    2006-01-01

    In early modern Venice, establishing the cause of a disease was critical to determining the appropriate cure: natural remedies for natural illnesses, spiritual solutions for supernatural or demonic ones. One common ailment was the French disease (syphilis), widely distributed throughout Venice's neighborhoods and social hierarchy, and evenly distributed between men and women. The disease was widely regarded as curable by the mid-sixteenth century, and cases that did not respond to natural remedies presented problems of interpretation to physicians and laypeople. Witchcraft was one possible explanation; using expert testimony from physicians, however, the Holy Office ruled out witchcraft as a cause of incurable cases and reinforced perceptions that the disease was of natural origin. Incurable cases were explained as the result of immoral behavior, thereby reinforcing the associated stigma. This article uses archival material from Venice's Inquisition records from 1580 to 1650, as well as mortality data.

  14. Spatial requirements of different life-stages of the loggerhead turtle (Caretta caretta) from a distinct population segment in the northern Gulf of Mexico

    USGS Publications Warehouse

    Lamont, Margaret M.; Putman, Nathan F.; Fujisaki, Ikuko; Hart, Kristen M.

    2015-01-01

    Many marine species have complex life histories that involve disparate developmental, foraging and reproductive habitats and a holistic assessment of the spatial requirements for different life stages is a challenge that greatly complicates their management. Here, we combined data from oceanographic modeling, nesting surveys, and satellite tracking to examine the spatial requirements of different life stages of Loggerhead Turtles (Caretta caretta) from a distinct population segment in the northern Gulf of Mexico. Our findings indicate that after emerging from nesting beaches in Alabama and Northwest Florida, hatchlings disperse widely and the proportion of turtles following a given route varies substantially through time, with the majority (mean of 74.4%) projected to leave the Gulf of Mexico. Adult females use neritic habitat throughout the northern and eastern Gulf of Mexico both during the inter-nesting phase and as post-nesting foraging areas. Movements and habitat use of juveniles and adult males represent a large gap in our knowledge, but given the hatchling dispersal predictions and tracks of post-nesting females it is likely that some Loggerhead Turtles remain in the Gulf of Mexico throughout their life. More than two-thirds of the Gulf provides potential habitat for at least one life-stage of Loggerhead Turtles. These results demonstrate the importance of the Gulf of Mexico to this Distinct Population Segment of Loggerhead Turtles. It also highlights the benefits of undertaking comprehensive studies of multiple life stages simultaneously: loss of individual habitats have the potential to affect several life stages thereby having long-term consequences to population recovery.

  15. Prognostic capability of different liver disease scoring systems for prediction of early mortality after transjugular intrahepatic portosystemic shunt creation.

    PubMed

    Gaba, Ron C; Couture, Patrick M; Bui, James T; Knuttinen, M Grace; Walzer, Natasha M; Kallwitz, Eric R; Berkes, Jamie L; Cotler, Scott J

    2013-03-01

    To compare the performance of various liver disease scoring systems in predicting early mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, eight scoring systems were used to grade liver disease in 211 patients (male-to-female ratio = 131:80; mean age, 54 y) before TIPS creation from 1999-2011. Scoring systems included bilirubin level, Child-Pugh (CP) score, Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease sodium (MELD-Na) score, Emory score, prognostic index (PI), Acute Physiology and Chronic Health Evaluation (APACHE) 2 score, and Bonn TIPS early mortality (BOTEM) score. Medical record review was used to identify 30-day and 90-day clinical outcomes. The relationship of scoring parameters with mortality outcomes was assessed with multivariate analysis, and the relative ability of systems to predict mortality after TIPS creation was evaluated by comparing area under receiver operating characteristic (AUROC) curves. TIPS were successfully created for variceal hemorrhage (n = 121), ascites (n = 72), hepatic hydrothorax (n = 15), and portal vein thrombosis (n = 3). All scoring systems had a significant association with 30-day and 90-day mortality (P<.050 in each case) on multivariate analysis. Based on 30-day and 90-day AUROC, MELD (0.878, 0.816) and MELD-Na (0.863, 0.823) scores had the best capability to predict early mortality compared with bilirubin (0.786, 0.749), CP (0.822, 0.771), Emory (0.786, 0.681), PI (0.854, 0.760), APACHE 2 (0.836, 0.735), and BOTEM (0.798, 0.698), with statistical superiority over bilirubin, Emory, and BOTEM scores. Several liver disease scoring systems have prognostic value for early mortality after TIPS creation. MELD and MELD-Na scores most effectively predict survival after TIPS creation. Copyright © 2013. Published by Elsevier Inc.

  16. Identification of sero-reactive antigens for the early diagnosis of Johne’s disease in cattle

    PubMed Central

    Randall, Arlo; Grohn, Yrjo T.; Katani, Robab; Schilling, Megan; Radzio-Basu, Jessica

    2017-01-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), a chronic intestinal inflammatory disease of cattle and other ruminants. JD has a high herd prevalence and causes serious animal health problems and significant economic loss in domesticated ruminants throughout the world. Since serological detection of MAP infected animals during the early stages of infection remains challenging due to the low sensitivity of extant assays, we screened 180 well-characterized serum samples using a whole proteome microarray from Mycobacterium tuberculosis (MTB), a close relative of MAP. Based on extensive testing of serum and milk samples, fecal culture and qPCR for direct detection of MAP, the samples were previously assigned to one of 4 groups: negative low exposure (n = 30, NL); negative high exposure (n = 30, NH); fecal positive, ELISA negative (n = 60, F+E-); and fecal positive, ELISA positive (n = 60, F+E+). Of the 740 reactive proteins, several antigens were serologically recognized early but not late in infection, suggesting a complex and dynamic evolution of the MAP humoral immune response during disease progression. Ordinal logistic regression models identified a subset of 47 candidate proteins with significantly different normalized intensity values (p<0.05), including 12 in the NH and 23 in F+E- groups, suggesting potential utility for the early detection of MAP infected animals. Next, the diagnostic utility of four MAP orthologs (MAP1569, MAP2942c, MAP2609, and MAP1272c) was assessed and reveal moderate to high diagnostic sensitivities (range 48.3% to 76.7%) and specificity (range 96.7% to 100%), with a combined 88.3% sensitivity and 96.7% specificity. Taken together, the results of our analyses have identified several candidate MAP proteins of potential utility for the early detection of MAP infection, as well individual MAP proteins that may serve as the foundation for the next generation of well-defined serological

  17. CSF N-glycoproteomics for early diagnosis in Alzheimer's disease.

    PubMed

    Palmigiano, Angelo; Barone, Rita; Sturiale, Luisa; Sanfilippo, Cristina; Bua, Rosaria Ornella; Romeo, Donata Agata; Messina, Angela; Capuana, Maria Luisa; Maci, Tiziana; Le Pira, Francesco; Zappia, Mario; Garozzo, Domenico

    2016-01-10

    This work aims at exploring the human CSF (Cerebrospinal fluid) N-glycome by MALDI MS techniques, in order to assess specific glycosylation pattern(s) in patients with Alzheimer's disease (n:24) and in subjects with mild cognitive impairment (MCI) (n:11), these last as potential AD patients at a pre-dementia stage. For comparison, 21 healthy controls were studied. We identified a group of AD and MCI subjects (about 40-50% of the studied sample) showing significant alteration of CSF N-glycome profiling, consisting of a decrease in the overall sialylation degree and an increase in species bearing bisecting GlcNAc. Noteworthy, all the MCI patients that converted to AD within the clinical follow-up, had an abnormal CSF glycosylation profile. Based on the studied cohort, CSF glycosylation changes may occur before an AD clinical onset. Previous studies specifically focused on the key role of glycosyltransferase GnT-III on AD-pathogenesis, addressing the patho-mechanism to specific sugar modification of BACE-1 glycoprotein with bisecting GlcNAc. Our patients addressed protein N-glycosylation changes at an early phase of the whole biomolecular misregulation on AD, pointing to CSF N-glycome analyses as promising tool to enhance early detection of AD and also suggesting alternative therapeutics target molecules, such as specific glyco-enzymes. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Critical Dysphagia is Common in Parkinson Disease and Occurs Even in Early Stages: A Prospective Cohort Study.

    PubMed

    Pflug, Christina; Bihler, Moritz; Emich, Katharina; Niessen, Almut; Nienstedt, Julie Cläre; Flügel, Till; Koseki, Jana-Christiane; Plaetke, Rosemarie; Hidding, Ute; Gerloff, Christian; Buhmann, Carsten

    2018-02-01

    To assess the prevalence of dysphagia and its typical findings in unselected "real-world" Parkinson patients using an objective gold-standard method. This was a prospective, controlled, cross-sectional study conducted in 119 consecutive Parkinson patients of all stages independent of subjective dysphagia. Patients and 32 controls were clinically and endoscopically examined by flexible endoscopic evaluation of swallowing (FEES) to evaluate the deglutition with regard to three consistencies (water, biscuit, and bread). Typical findings of dysphagia like penetration and aspiration, residues, and leakage were assessed. Dysphagia was common in Parkinson patients and occurred in all, even early, disease stages. Only 5% (6/119) of patients showed a completely unremarkable deglutition. Aspiration was seen in 25% (30/119) of patients and always related to water. Residues occurred in 93% (111/119), most commonly for bread. Leakage was much less frequent and was found in only 3-18%, depending on consistency. In a significant fraction of patients, objective dysphagia was not subjectively perceived. A total of 16% of asymptomatic patients suffered from critical aspiration. Significant swallowing deficiencies already occurred in early disease. Aspiration was found in 4 of 20 (20%) patients with disease duration of less than 2 years. Seven of 57 patients (12%) with Hoehn and Yahr stage 2 suffered from severe aspiration. Given the high frequency of critical aspiration in Parkinson disease, these patients should be evaluated early for dysphagia to avoid complications and recommend an adequate therapy. FEES is a simple, cost efficient, minimally invasive method that is ideally suited for this purpose.

  19. Which medical and social decision topics are important after early diagnosis of Alzheimer's Disease from the perspectives of people with Alzheimer's Disease, spouses and professionals?

    PubMed

    Bronner, Katharina; Perneczky, Robert; McCabe, Rose; Kurz, Alexander; Hamann, Johannes

    2016-03-08

    The relevance of early decision making will rise with increasing availability of early detection of Alzheimer's disease (AD) using brain imaging or biomarkers. Five people with mild AD, six relatives and 13 healthcare professionals with experience in the management of AD were interviewed in a qualitative study regarding medical and social decision topics that emerge after early diagnosis of Alzheimer's disease. Medical treatment, assistance in everyday life and legal issues emerged as the main decision topics after an early diagnosis of AD. People with AD mostly got in contact with the health and social care system through the initiative of their spouses. They were usually aware of their illness and most received antidementia drugs and/or behavioural interventions. Following diagnosis people with AD received support by their spouses. Healthcare professionals were aware of the risk of excessive demand on relatives due to supporting their family member with AD. In the opinion of healthcare professionals legal issues should be arranged in time before patients lose their decisional capacity. In addition, people with AD and spouses reported various coping strategies, in particular "carry on as normal" after diagnosis but mostly are reluctant to actively plan for future stages of the disease. Due to the common desire to "carry on as usual" after a diagnosis of AD, many people with AD and spouses may miss the opportunity to discuss and decide on important medical and social topics. A structured approach e.g. a decision aid might support people with AD and spouses in their decision making process and thereby preserve persons' with AD autonomy before they lose the capacity in decision-making.

  20. Comparison of males versus females with culture-confirmed early Lyme disease at presentation and at 11-20 years after diagnosis.

    PubMed

    Weitzner, Erica; Visintainer, Paul; Wormser, Gary P

    2016-08-01

    Lyme disease is the most common vector-borne infection in the United States with 300,000 estimated cases per year. The purpose of this study was to compare the presenting clinical features and long-term outcome of males versus females with culture-confirmed early Lyme disease. 174 males and 109 females with culture-confirmed erythema migrans were entered into a prospective study with follow-up visits scheduled at six months, 12 months and annually thereafter for up to 20 years. Males and females with early Lyme disease had a similar likelihood of having multiple erythema migrans skin lesions and had a similar number of additional subjective symptoms, such as fatigue, at study entry. Among the 71 males and 57 females able to be followed up for 11-20 years, there were no significant differences in baseline symptoms, rate of seroreactivity to Borrelia burgdorferi, or in frequency of post-treatment symptoms. Females, however, were significantly more likely than males to return for follow-up visits (P = 0.0003). Males and females with culture-confirmed early Lyme disease had similar clinical features, rates of seropositivity, and long-term outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Predictors of driving safety in early Alzheimer disease

    PubMed Central

    Dawson, J D.; Anderson, S W.; Uc, E Y.; Dastrup, E; Rizzo, M

    2009-01-01

    Objective: To measure the association of cognition, visual perception, and motor function with driving safety in Alzheimer disease (AD). Methods: Forty drivers with probable early AD (mean Mini-Mental State Examination score 26.5) and 115 elderly drivers without neurologic disease underwent a battery of cognitive, visual, and motor tests, and drove a standardized 35-mile route in urban and rural settings in an instrumented vehicle. A composite cognitive score (COGSTAT) was calculated for each subject based on eight neuropsychological tests. Driving safety errors were noted and classified by a driving expert based on video review. Results: Drivers with AD committed an average of 42.0 safety errors/drive (SD = 12.8), compared to an average of 33.2 (SD = 12.2) for drivers without AD (p < 0.0001); the most common errors were lane violations. Increased age was predictive of errors, with a mean of 2.3 more errors per drive observed for each 5-year age increment. After adjustment for age and gender, COGSTAT was a significant predictor of safety errors in subjects with AD, with a 4.1 increase in safety errors observed for a 1 SD decrease in cognitive function. Significant increases in safety errors were also found in subjects with AD with poorer scores on Benton Visual Retention Test, Complex Figure Test-Copy, Trail Making Subtest-A, and the Functional Reach Test. Conclusion: Drivers with Alzheimer disease (AD) exhibit a range of performance on tests of cognition, vision, and motor skills. Since these tests provide additional predictive value of driving performance beyond diagnosis alone, clinicians may use these tests to help predict whether a patient with AD can safely operate a motor vehicle. GLOSSARY AD = Alzheimer disease; AVLT = Auditory Verbal Learning Test; Blocks = Block Design subtest; BVRT = Benton Visual Retention Test; CFT = Complex Figure Test; CI = confidence interval; COWA = Controlled Oral Word Association; CS = contrast sensitivity; FVA = far visual

  2. An Overview of Inflammatory Bowel Disease: General Consideration and Genetic Screening Approach in Diagnosis of Early Onset Subsets

    PubMed Central

    Nemati, Shahram; Teimourian, Shahram

    2017-01-01

    Inflammatory bowel disease (IBD) is the consequence of an aberrant hemostasis of the immune cells at the gut mucosal border. Based on clinical manifestation, laboratory tests, radiological studies, endoscopic and histological features, this disease is divided into three main types including Crohn’s disease (CD), Ulcerative colitis (UC), and IBDunclassified (IBD-U). IBD is frequently presented in adults, but about 20% of IBD cases are diagnosed during childhood called pediatric IBD (PIBD). Some patients in the latter group emerge the first symptoms during infancy or under 5 years of age named infantile and very early onset IBD (VEO-IBD), respectively. These subtypes make a small fraction of PIBD, but they have exclusive phenotypic and genetic characteristics such that they are accompanied by severe disease course and resistance to conventional therapy. In this context, understanding the underlying molecular pathology opens a promising field for individualized and effective treatment. Here, we describe current hypotheses on IBD pathophysiology then explain the new idea about genetic screening technology as a good potential approach to identify the causal variants early in the disease manifestation, which is especially important for the fast and accurate treatment of VEO-IBD. PMID:28638582

  3. [Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

    PubMed

    Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

    2013-01-01

    A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

  4. Standardized Symptom Measurement of Individuals with Early Lyme Disease Over Time.

    PubMed

    Bechtold, Kathleen T; Rebman, Alison W; Crowder, Lauren A; Johnson-Greene, Doug; Aucott, John N

    2017-03-01

    Understanding the Lyme disease (LD) literature is challenging given the lack of consistent methodology and standardized measurement of symptoms and the impact on functioning. This prospective study incorporates well-validated measures to capture the symptom picture of individuals with early LD from time of diagnosis through 6-months post-treatment. One hundred seven patients with confirmed early LD and 26 healthy controls were evaluated using standardized instruments for pain, fatigue, depressive symptoms, functional impact, and cognitive functioning. Prior to antibiotic treatment, patients experience notable symptoms of fatigue and pain statistically higher than controls. After treatment, there are no group differences, suggesting that symptoms resolve and that there are no residual cognitive impairments at the level of group analysis. However, using subgroup analyses, some individuals experience persistent symptoms that lead to functional decline and these individuals can be identified immediately post-completion of standard antibiotic treatment using well-validated symptom measures. Overall, the findings suggest that ideally-treated early LD patients recover well and experience symptom resolution over time, though a small subgroup continue to suffer with symptoms that lead to functional decline. The authors discuss use of standardized instruments for identification of individuals who warrant further clinical follow-up. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Daily Intake of Milk Powder and Risk of Celiac Disease in Early Childhood: A Nested Case-Control Study.

    PubMed

    Hård Af Segerstad, Elin M; Lee, Hye-Seung; Andrén Aronsson, Carin; Yang, Jimin; Uusitalo, Ulla; Sjöholm, Ingegerd; Rayner, Marilyn; Kurppa, Kalle; Virtanen, Suvi M; Norris, Jill M; Agardh, Daniel

    2018-04-28

    Milk powder and gluten are common components in Swedish infants' diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls matched for sex, birth year, and HLA genotype, was performed on a birth cohort of HLA-DR3-DQ2 and/or DR4-DQ8-positive children. Subjects were screened annually for celiac disease using tissue transglutaminase autoantibodies (tTGA). Three-day food records estimated the mean intake of milk powder at ages 6 months, 9 months, 12 months, 18 months, and 24 months. Conditional logistic regression calculated odds ratios (OR) at last intake prior to seroconversion of tTGA positivity, and for each time-point respectively and adjusted for having a first-degree relative with celiac disease and gluten intake. Intake of milk powder prior to seroconversion of tTGA positivity was not associated with celiac disease (OR = 1.00; 95% CI = 0.99, 1.03; p = 0.763). In conclusion, intake of milk powder in early childhood is not associated with celiac disease in genetically susceptible children.

  6. Coronary Artery Disease and Reticular Macular Disease, a Subphenotype of Early Age-Related Macular Degeneration.

    PubMed

    Cymerman, Rachel M; Skolnick, Adam H; Cole, William J; Nabati, Camellia; Curcio, Christine A; Smith, R Theodore

    2016-11-01

    Reticular macular disease (RMD) is the highest risk form of early age-related macular degeneration and also specifically confers decreased longevity. However, because RMD requires advanced retinal imaging for adequate detection of its characteristic subretinal drusenoid deposits (SDD), it has not yet been completely studied with respect to coronary artery disease (CAD), the leading cause of death in the developed world. Because CAD appears in middle age, our purpose was to screen patients aged 45-80 years, documented either with or without CAD, to determine if CAD is associated with RMD. A prospective cohort study of patients with documented CAD status and no known retinal disease in a clinical practice setting at one institution. Subjects and Controls: A number of 76 eyes from 38 consecutive patients (23 with documented CAD, 15 controls documented without CAD; 47.4% female; mean age 66.7 years). Patients were imaged with near-infrared reflectance/spectral domain optical coherence tomography and assessed in masked fashion by two graders for the presence of SDD lesions of RMD and soft drusen. Presence or absence of RMD/SDD and soft drusen. RMD was more frequent in patients with CAD versus those without (Relative Risk [RR] = 2.1, CI = 1.08-3.95, P = 0.03). There was no association of CAD with soft drusen. A specific relationship between CAD and RMD suggests common systemic causes for both and warrants further study.

  7. Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases.

    PubMed

    Pavletic, Adriana J; Marques, Adriana R

    2017-07-15

    False-positive serology for Lyme disease was reported in patients with acute infectious mononucleosis. Here we describe 2 patients with early disseminated Lyme disease who were misdiagnosed with infectious mononucleosis based on false-positive tests for primary Epstein-Barr virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  8. [Early coronary heart disease together with tyoe II diabetes mellitus in persons of Hindustani origin].

    PubMed

    Bongers, I; Westendorp, R G; Stolk, B; Huysmans, H A; Vandenbroucke, J P

    1995-01-07

    To investigate the association between early coronary heart disease and non insulin dependent diabetes mellitus in South Asian patients in the Netherlands, a homogeneous population which descends from Indian immigrants to Surinam in the late nineteenth century. Case control study. University hospital Leiden. South Asian patients (n = 38) and control patients (n = 76) were identified in an automated data base comprising all patients who had aortocoronary surgery in the period January 1st 1990 to January 1st 1993. Control patients were from the general population and matched for calendar time. Patients' characteristics such as the onset of coronary heart disease and the presence of non insulin dependent diabetes mellitus were obtained from the medical records at the time of surgery. The onset of coronary heart disease in South Asian patients occurred about eight years earlier than in control patients (49.8 versus 58.2 years; 95% confidence interval of the difference: 4.3-12.5). Non insulin dependent diabetes mellitus was about four times more frequent in South Asian patients (50% versus 13%; 19-54). This difference was the same after correction for differences in sex, age, and body mass index. Diabetes mellitus caused by insulin resistance significantly contributes to early coronary heart disease in South Asian immigrant patients, in accordance with the literature on the present population of India. These findings strengthen the belief that genetic factor are important in the development of insulin resistance and atherosclerosis.

  9. Direct Molecular Detection and Genotyping of Borrelia burgdorferi from Whole Blood of Patients with Early Lyme Disease

    PubMed Central

    Eshoo, Mark W.; Crowder, Christopher C.; Rebman, Alison W.; Rounds, Megan A.; Matthews, Heather E.; Picuri, John M.; Soloski, Mark J.; Ecker, David J.; Schutzer, Steven E.; Aucott, John N.

    2012-01-01

    Direct molecular tests in blood for early Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre-enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus PCR and electrospray ionization mass spectrometry detection assay. We evaluated the assay on blood collected at the initial presentation from 21 endemic area patients who had both physician-diagnosed erythema migrans (EM) and positive two-tiered serology either at the initial visit or at a follow-up visit after three weeks of antibiotic therapy. Results of this DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided the B. burgdorferi genotype. The combined results of our direct detection assay with initial physician visit serology resulted in the detection of early Lyme disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we demonstrate the ability to detect B. burgdorferi in early Lyme disease directly from whole blood specimens prior to seroconversion. PMID:22590620

  10. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease

    PubMed Central

    Zetterberg, Henrik; Mattsson, Niklas; Johansson, Per; Minthon, Lennart; Blennow, Kaj; Olsson, Mattias

    2015-01-01

    Objective: To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). Methods: From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study. Results: The best CSF measures for identifying MCI-AD were Aβ42/total tau (t-tau) and Aβ42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93–0.94). The best PET measures performed similarly (AUC 0.92–0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03–0.12, p < 0.05). Using nonoptimized cutoffs, CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately. Conclusions: Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy. Classification of evidence: This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately. PMID:26354982

  11. Association Between Early Helicobacter pylori Eradication and a Lower Risk of Recurrent Complicated Peptic Ulcers in End-Stage Renal Disease Patients

    PubMed Central

    Chang, Shen-Shong; Hu, Hsiao-Yun

    2015-01-01

    Abstract End-stage renal disease (ESRD) patients exhibit an increased incidence of peptic ulcer disease. Helicobacter pylori plays a central role in the development of peptic ulcers. The effect of early H pylori eradication on the recurrence of complicated peptic ulcer disease in ESRD patients remains unclear. The aim of the present study was to explore whether early H pylori eradication therapy in ESRD patients can reduce the risk of recurrent complicated peptic ulcers. We conducted a population-based cohort study and recruited patients with ESRD who had developed peptic ulcers. We categorized patients into early (time lag ≦120 days after peptic ulcer diagnosis) and late H pylori eradication therapy groups. The Cox proportional hazards model was used. The endpoint was based on hospitalization for complicated recurrent peptic ulcers. The early and late H pylori eradication therapy groups consisted of 2406 and 1356 ESRD patients, respectively, in a time lag of 120 days. After adjusting for possible confounders, the early eradication group exhibited a lower rate of complicated recurrent peptic ulcer disease (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.64–0.91, P = 0.003) in a time lag of ≦120 days, but a similar rate of complicated recurrent peptic ulcer disease in time lags of ≦1 year (HR = 0.97, 95% CI 0.79–1.19, P = 0.758) and 2 years (HR = 1.11, 95% CI 0.86–1.44, P = 0.433) compared with the late eradication group. We recommend administering H pylori eradication within 120 days after peptic ulcer diagnosis to H pylori infected ESRD patients who have developed peptic ulcers. PMID:25569660

  12. Gut microbiota in early life and its influence on health and disease: A position paper by the Malaysian Working Group on Gastrointestinal Health.

    PubMed

    Lee, Yeong Yeh; Hassan, Siti Asma; Ismail, Intan Hakimah; Chong, Sze Yee; Raja Ali, Raja Affendi; Amin Nordin, Syafinaz; Lee, Way Seah; Majid, Noorizan Abdul

    2017-12-01

    The role of gut microbiota in early life and its impact on gut health and subsequent diseases remain unclear. There is a lack of research and awareness in this area, especially in the Asia-Pacific region, including Malaysia. This paper reports the position of a Malaysian Working Group on some key issues surrounding gut microbiota in early life and its role in gut health and diseases, as well as experts' stand on probiotics and prebiotics. The group reached a consensus that certain factors, including elective caesarean; premature deliveries; complementary feeding; use of antibiotics, prebiotics and/or probiotics; and exposure to the external environmental, have an impact on gut microbiota in early life. However, as evidence is lacking, especially from the Asia-Pacific region, further studies are needed to understand how gut microbiota in early life affects subsequent diseases, including allergy, inflammatory bowel disease, obesity and infantile colic. Lastly, although beneficial in acute diarrhoeal disease and probably allergic eczema, probiotics (and/or prebiotics) should be used cautiously in other gut dysbiotic conditions until more data are available. © 2017 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  13. Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease.

    PubMed

    Aziz, Anne-Laure; Giusiano, Bernard; Joubert, Sven; Duprat, Lauréline; Didic, Mira; Gueriot, Claude; Koric, Lejla; Boucraut, José; Felician, Olivier; Ranjeva, Jean-Philippe; Guedj, Eric; Ceccaldi, Mathieu

    2017-06-01

    Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. [An early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development].

    PubMed

    Abe, Koji

    2018-03-28

    The present review focuses an early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development. In relation to foreign previous reports, five topics are introduced and discussed on ALS with dementia, ALS/Parkinsonism dementia complex (ALS/PDC), familial ALS (FALS), spinal bulbar muscular atrophy (SBMA), and multisystem involvement especially in cerebellar system of ALS including ALS/SCA (spinocerebellar ataxia) crossroad mutation Asidan. This review found the great contribution of Japanese reports on the above five topics, and confirmed the great development of ALS-related diseases over the past 120 years.

  15. Early versus delayed erythropoietin for the anaemia of end-stage kidney disease.

    PubMed

    Coronado Daza, Jorge; Martí-Carvajal, Arturo J; Ariza García, Amaury; Rodelo Ceballos, Joaquín; Yomayusa González, Nancy; Páez-Canro, Carol; Loza Munárriz, César; Urrútia, Gerard

    2015-12-16

    Anaemia is a common complication in people with chronic kidney disease (CKD) and mainly develops as a consequence of relative erythropoietin (EPO) deficiency. Anaemia develops early in the course of disease and peaks among people with end-stage kidney disease (ESKD). Many types of EPO - also called erythropoiesis-stimulating agents (ESAs) - are used to treat anaemia in people with ESKD.ESAs have changed treatment of severe anaemia among people with CKD by relieving symptoms and avoiding complications associated with blood transfusion. However, no benefits have been found in relation to mortality rates and non-cardiac fatal events, except quality of life. Moreover, a relationship between ESA use and increased cardiovascular morbidity and mortality in patients with CKD has been reported in studies with fully correcting anaemia comparing with partial anaemia correction. Until 2012, guidelines recommended commencing ESA treatment when haemoglobin was less than 11 g/dL; the current recommendation is EPO commencement when haemoglobin is between 9 and 10 g/dL. However, advantages in commencing therapy when haemoglobin levels are greater than 10 g/dL but less than 11 g/dL remain unknown, especially among older people whose life expectancy is limited, but in whom EPO therapy may improve quality of life. To assess the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis We searched the Cochrane Kidney and Transplant Specialised Register to 8 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating at the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis. Studies comparing EPO with another EPO, placebo or no treatment were eligible for inclusion. It was planned that two

  16. Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants.

    PubMed

    McIntosh, Lindsey G; Mannava, Sishir; Camalier, Corrie R; Folley, Bradley S; Albritton, Aaron; Konrad, Peter E; Charles, David; Park, Sohee; Neimat, Joseph S

    2014-01-01

    Parkinson's disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD) were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT), or drug therapy plus STN-DBS (ODT + DBS). Matched healthy elderly controls (HEC) and young controls (HYC) also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT + DBS) nor therapy state (ON/OFF) altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

  17. R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

    PubMed

    Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

    2012-05-09

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

  18. Early response to therapy predicts 6-month and 1-year disease activity outcomes in psoriatic arthritis patients.

    PubMed

    Schoels, Monika M; Landesmann, Uriel; Alasti, Farideh; Baker, Daniel; Smolen, Josef S; Aletaha, Daniel

    2018-06-01

    In PsA management, remission and low disease activity represent preferential treatment targets. We aimed at evaluating the predictive value and clinical use of initial therapeutic response for subsequent achievement of these targets. Based on data of 216 patients enrolled in a randomized controlled trial of golimumab (GO-REVEAL), we performed diagnostic testing analyses using 3- and 6-month disease activity as tests for treatment outcomes to understand the implications of early response. In regression analyses, we estimated the probabilities for achieving at least LDA. Disease activity was measured by the disease activity index for PsA (DAPSA). Three-month DAPSA levels were excellent tests for disease activity at 6 months (and at 1 year), with areas under the receiver operating characteristic curves of 0.92 (and 0.88, respectively). The estimated probability for 6-month LDA could be quantified as <22% if patients did not reach at least moderate disease activity after 3 months on golimumab. Similar data were seen for early DAPSA response: patients achieving a DAPSA 85% at 3 months had an 84% probability for 6-month LDA or REM. All results were validated in an independent trial cohort of patients treated with infliximab (IMPACT 2). Three months after implementation of therapy in PsA, it is already possible to evaluate the potential for accomplishing therapeutic goals. This substantiates the choice of the 3-month assessment as essential for treatment adaptations.

  19. Zoonotic viral diseases and the frontier of early diagnosis, control and prevention.

    PubMed

    Heeney, J L

    2006-11-01

    Public awareness of the human health risks of zoonotic infections has grown in recent years. Currently, concern of H5N1 flu transmission from migratory bird populations has increased with foci of fatal human cases. This comes on the heels of other major zoonotic viral epidemics in the last decade. These include other acute emerging or re-emerging viral diseases such as severe acute respiratory syndrome (SARS), West-Nile virus, Ebola virus, monkeypox, as well as the more inapparent insidious slow viral and prion diseases. Virus infections with zoonotic potential can become serious killers once they are able to establish the necessary adaptations for efficient human-to-human transmission under circumstances sufficient to reach epidemic proportions. The monitoring and early diagnosis of these potential risks are overlapping frontiers of human and veterinary medicine. Here, current viral zoonotics and evolving threats are reviewed.

  20. Alzheimer's disease prevention: from risk factors to early intervention.

    PubMed

    Crous-Bou, Marta; Minguillón, Carolina; Gramunt, Nina; Molinuevo, José Luis

    2017-09-12

    Due to the progressive aging of the population, Alzheimer's disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild-moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant.In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. Secondly, we review the development of public-private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment.The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer's dementia for only a few years, would have a huge impact on public health.

  1. Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease.

    PubMed

    Llorens-Martín, Maria; Blazquez-Llorca, Lidia; Benavides-Piccione, Ruth; Rabano, Alberto; Hernandez, Felix; Avila, Jesus; DeFelipe, Javier

    2014-01-01

    A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer's disease (AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII → dentate gyrus → CA3 → CA1) and monosynaptic (ECIII → CA1) circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

  2. Transdermal rotigotine in early stage Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Mizuno, Yoshikuni; Nomoto, Masahiro; Kondo, Tomoyoshi; Hasegawa, Kazuko; Murata, Miho; Takeuchi, Masahiro; Ikeda, Junji; Tomida, Takayuki; Hattori, Nobutaka

    2013-09-01

    We conducted a randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of transdermal rotigotine at doses up to 16 mg/24 hours in patients with early stage Parkinson's disease (PD) in Japan. Patients received once-daily rotigotine 2 to 16 mg/24 hours (mean dose, 12.8 mg/24 hours; n = 82) or placebo (n = 90) for 12 weeks. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) and part III (motor function) scores from baseline to the end of treatment. The mean (± standard deviation) changes in UPDRS part II and III scores were -8.4 ± 9.7 in the rotigotine group and -4.1 ± 8.2 in the placebo group and were significantly different (P = 0.002). More patients in the rotigotine group than in the placebo group had a ≥ 20% score reduction. No serious drug-related adverse events were reported. Rotigotine at doses up to 16 mg/24 hours was well tolerated and improved function in patients with early stage PD. © 2013 International Parkinson and Movement Disorder Society.

  3. Acid stress mediated adaptive divergence in ion channel function during embryogenesis in Rana arvalis

    PubMed Central

    Shu, Longfei; Laurila, Anssi; Räsänen, Katja

    2015-01-01

    Ion channels and pumps are responsible for ion flux in cells, and are key mechanisms mediating cellular function. Many environmental stressors, such as salinity and acidification, are known to severely disrupt ionic balance of organisms thereby challenging fitness of natural populations. Although ion channels can have several vital functions during early life-stages (e.g. embryogenesis), it is currently not known i) how developing embryos maintain proper intracellular conditions when exposed to environmental stress and ii) to what extent environmental stress can drive intra-specific divergence in ion channels. Here we studied the moor frog, Rana arvalis, from three divergent populations to investigate the role of different ion channels and pumps for embryonic survival under acid stress (pH 4 vs 7.5) and whether populations adapted to contrasting acidities differ in the relative role of different ion channel/pumps. We found that ion channels that mediate Ca2+ influx are essential for embryonic survival under acidic pH, and, intriguingly, that populations differ in calcium channel function. Our results suggest that adaptive divergence in embryonic acid stress tolerance of amphibians may in part be mediated by Ca2+ balance. We suggest that ion flux may mediate adaptive divergence of natural populations at early life-stages in the face of environmental stress. PMID:26381453

  4. Early-Onset Autoimmune Disease as a Manifestation of Primary Immunodeficiency

    PubMed Central

    Carneiro-Sampaio, Magda; Coutinho, Antonio

    2015-01-01

    Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-α pathway (in Aicardi–Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID. PMID:25999944

  5. The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*

    PubMed Central

    2014-01-01

    Respiratory diseases in Italy already now represent an emergency (they are the 3rd ranking cause of death in the world, and the 2nd if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual’s risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable to

  6. The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*.

    PubMed

    Nardini, Stefano; Annesi-Maesano, Isabella; Del Donno, Mario; Delucchi, Maurizio; Bettoncelli, Germano; Lamberti, Vincenzo; Patera, Carlo; Polverino, Mario; Russo, Antonio; Santoriello, Carlo; Soverina, Patrizio

    2014-01-01

    Respiratory diseases in Italy already now represent an emergency (they are the 3(rd) ranking cause of death in the world, and the 2(nd) if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual's risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable

  7. Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging.

    PubMed

    van de Haar, Harm J; Jansen, Jacobus F A; van Osch, Matthias J P; van Buchem, Mark A; Muller, Majon; Wong, Sau May; Hofman, Paul A M; Burgmans, Saartje; Verhey, Frans R J; Backes, Walter H

    2016-09-01

    The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Early Life Stress, Depression And Parkinson's Disease: A New Approach.

    PubMed

    Dallé, Ernest; Mabandla, Musa V

    2018-03-19

    This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression. Therefore, since PD causes depletion of dopaminergic neurons in the substantia nigra, depression, rather than being just a simple mood disorder, may be part of the pathophysiological process that leads to PD. It is plausible that the mesocortical and mesolimbic dopaminergic pathways that mediate mood, emotion, and/or cognitive function may also play a key role in depression associated with PD. Here, we propose that a medication designed to address a deficiency in serotonin is more likely to influence motor symptoms of PD associated with depression. This review highlights the effects of an antidepressant, Fluvoxamine maleate, in an animal model that combines depressive-like symptoms and Parkinsonism.

  9. Cost-effectiveness of neurostimulation in Parkinson's disease with early motor complications.

    PubMed

    Dams, Judith; Balzer-Geldsetzer, Monika; Siebert, Uwe; Deuschl, Günther; Schuepbach, W M Michael; Krack, Paul; Timmermann, Lars; Schnitzler, Alfons; Reese, Jens-Peter; Dodel, Richard

    2016-08-01

    Recent research efforts have focused on the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild-to-moderate PD experiencing motor complications. We assessed the cost utility of subthalamic DBS compared with the best medical treatment for German patients below the age of 61 with early motor complications of PD. We applied a previously published Markov model that integrated health utilities based on EuroQoL and direct costs over patients' lifetime adjusted to the German health care payer perspective (year of costing: 2013). Effectiveness was evaluated using the Parkinson's Disease Questionnaire 39 summary index. We performed sensitivity analyses to assess uncertainty. In the base-case analysis, the incremental cost-utility ratio for STN DBS compared to best medical treatment was 22,700 Euros per quality-adjusted life year gained. The time to, and costs for, battery exchange had a major effect on the incremental cost-utility ratios, but never exceeded a threshold of 50,000 Euros per quality-adjusted life year. Our decision analysis supports the fact that STN DBS at earlier stages of the disease is cost-effective in patients below the age of 61 when compared with the best medical treatment in the German health care system. This finding was supported by detailed sensitivity analyses reporting robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to medical therapy with respect to quality of life for patients with early motor complications, this further analysis has shown its cost-effectiveness. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  10. Application of multispectral reflectance for early detection of tomato disease

    NASA Astrophysics Data System (ADS)

    Xu, Huirong; Zhu, Shengpan; Ying, Yibin; Jiang, Huanyu

    2006-10-01

    Automatic diagnosis of plant disease is important for plant management and environmental preservation in the future. The objective of this study is to use multispectral reflectance measurements to make an early discrimination between the healthy and infected plants by the strain of tobacco mosaic virus (TMV-U1) infection. There were reflectance changes in the visible (VIS) and near infrared spectroscopy (NIR) between the healthy and infected plants. Discriminant models were developed using discriminant partial least squares (DPLS) and Mahalanobis distance (MD). The DPLS models had a root mean square error of calibration (RMSEC) of 0.397 and correlation coefficient (r) of 0.59 and the MD model correctly classified 86.7% healthy plants and up to 91.7% infected plants.

  11. Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions.

    PubMed

    Loranger, Hannah; Zotz, Gerhard; Bader, Maaike Y

    2016-01-01

    On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics. © The Authors 2016. Published by Oxford University Press on behalf of the Annals of Botany Company.

  12. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

    PubMed Central

    2011-01-01

    Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be

  13. Early-life antibiotic use and subsequent diagnosis of food allergy and allergic diseases.

    PubMed

    Hirsch, A G; Pollak, J; Glass, T A; Poulsen, M N; Bailey-Davis, L; Mowery, J; Schwartz, B S

    2017-02-01

    Antibiotic use in early life has been linked to disruptions in the microbiome. Such changes can disturb immune system development. Differences have been observed in the microbiota of children with and without allergies, but there have been few studies on antibiotic use and allergic disease. We evaluated associations of early-life antibiotic use with subsequent occurrence of food allergy and other allergies in childhood using electronic health record data. We used longitudinal data on 30 060 children up to age 7 years from Geisinger Clinic's electronic health record to conduct a sex- and age-matched case-control study to evaluate the association between antibiotic use and milk allergy, non-milk food allergies, and other allergies. For each outcome, we estimated conditional logistic regression models adjusting for race/ethnicity, history of Medical Assistance, and mode of birth delivery. Models were repeated separately for penicillins, cephalosporins and macrolides. There were 484 milk allergy cases, 598 non-milk food allergy cases and 3652 other allergy cases. Children with three or more antibiotic orders had a greater odds of milk allergy (Odds Ratio; 95% Confidence interval) (1.78; 1.28-2.48), non-milk food allergy (1.65; 1.27-2.14), and other allergies (3.07; 2.72-3.46) compared with children with no antibiotic orders. Associations were strongest at younger ages and differed by antibiotic class. We observed associations between antibiotic orders and allergic diseases, providing evidence of a potentially modifiable clinical practice associated with paediatric allergic disease. Differences by antibiotic class should be further explored, as this knowledge could inform paediatric treatment decisions. © 2016 John Wiley & Sons Ltd.

  14. Early Life Antibiotic Use and Subsequent Diagnosis of Food Allergy and Allergic Diseases

    PubMed Central

    Hirsch, Annemarie G.; Pollak, Jonathan; Glass, Thomas A.; Poulsen, Melissa N.; Bailey-Davis, Lisa; Mowery, Jacob; Schwartz, Brian S.

    2016-01-01

    Background Antibiotic use in early life has been linked to disruptions in the microbiome. Such changes can disturb immune system development. Differences have been observed in the microbiota of children with and without allergies, but there have been few studies on antibiotic use and allergic disease. Objective We evaluated associations of early-life antibiotic use with subsequent occurrence of food allergy and other allergies in childhood using electronic health record data. Methods We used longitudinal data on 30,060 children up to age 7 years from Geisinger Clinic’s electronic health record to conduct a sex and age matched case-control study to evaluate the association between antibiotic use and milk allergy, non-milk food allergies, and other allergies. For each outcome, we estimated conditional logistic regression models adjusting for race/ethnicity, history of Medical Assistance, and mode of birth delivery. Models were repeated separately for penicillins, cephalosporins, and macrolides. Results There were 484 milk allergy cases, 598 non-milk food allergy cases, and 3652 other allergy cases. Children with three or more antibiotic orders had a greater odds of milk allergy (odds ratio; 95% confidence interval) (1.78; 1.28–2.48), non-milk food allergy (1.65; 1.27–2.14), and other allergies (3.07; 2.72–3.46) compared to children with no antibiotic orders. Associations were strongest at younger ages and differed by antibiotic class. Conclusions and Clinical Relevance We observed associations between antibiotic orders and allergic diseases, providing evidence of a potentially modifiable clinical practice associated with pediatric allergic disease. Differences by antibiotic class should be further explored, as this knowledge could inform pediatric treatment decisions. PMID:27562571

  15. Alteration of diffusion-tensor MRI measures in brain regions involved in early stages of Parkinson's disease.

    PubMed

    Chen, Nan-Kuei; Chou, Ying-Hui; Sundman, Mark; Hickey, Patrick; Kasoff, Willard S; Bernstein, Adam; Trouard, Theodore P; Lin, Tanya; Rapcsak, Steven Z; Sherman, Scott J; Weingarten, Carol

    2018-06-07

    Many non-motor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion tensor imaging (DTI) is suitable for detecting changes of brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved ROI based analysis methods. Results showed that 1) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; 2) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

  16. A Framework for Assessing Health Risk of Environmental Exposures to Children (Final)

    EPA Science Inventory

    EPA released the final report entitled, A Framework for Assessing Health Risk of Environmental Exposures to Children, which examines the impact of potential exposures during developmental lifestages and subsequent lifestages, while emphasizing the iterative nature of the a...

  17. Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients.

    PubMed

    Rebman, Alison W; Crowder, Lauren A; Kirkpatrick, Allison; Aucott, John N

    2015-03-01

    Two-tier serology is often used to confirm a diagnosis of Lyme disease. One hundred and four patients with physician diagnosed erythema migrans rashes had blood samples taken before and after 3 weeks of doxycycline treatment for early Lyme disease. Acute and convalescent serologies for Borrelia burgdorferi were interpreted according to the 2-tier antibody testing criteria proposed by the Centers for Disease Control and Prevention. Serostatus was compared across several clinical and demographic variables both pre- and post-treatment. Forty-one patients (39.4%) were seronegative both before and after treatment. The majority of seropositive individuals on both acute and convalescent serology had a positive IgM western blot and a negative IgG western blot. IgG seroconversion on western blot was infrequent. Among the baseline variables included in the analysis, disseminated lesions (p < 0.0001), a longer duration of illness (p < 0.0001), and a higher number of reported symptoms (p = 0.004) were highly significantly associated with positive final serostatus, while male sex (p = 0.05) was borderline significant. This variability, and the lack of seroconversion in a subset of patients, highlights the limitations of using serology alone in identifying early Lyme disease. Furthermore, these findings underline the difficulty for rheumatologists in identifying a prior exposure to Lyme disease in caring for patients with medically unexplained symptoms or fibromyalgia-like syndromes.

  18. Memory retrieval by activating engram cells in mouse models of early Alzheimer's disease.

    PubMed

    Roy, Dheeraj S; Arons, Autumn; Mitchell, Teryn I; Pignatelli, Michele; Ryan, Tomás J; Tonegawa, Susumu

    2016-03-24

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.

  19. Efficacy of rasagiline in early Parkinson's disease: a meta-analysis of data from the TEMPO and ADAGIO studies.

    PubMed

    Hauser, Robert A; Abler, Victor; Eyal, Eli; Eliaz, Rom E

    2016-10-01

    To evaluate the efficacy of rasagiline versus placebo in a pooled population of patients with early Parkinson's disease (PD). TEMPO and ADAGIO were Phase III studies that evaluated the symptomatic efficacy of rasagiline versus placebo in patients with early PD. This meta-analysis included Unified Parkinson's Disease Rating Scale (UPDRS) observations from weeks 12, 24 and 36 in ADAGIO and from weeks 14 and 26 in TEMPO; TEMPO visits were recoded to weeks 12 and 24, respectively. The present analysis includes all patients who received rasagiline 1 mg/day, 2 mg/day or placebo, and had ≥1 post-baseline observations and a subgroup of patients whose baseline UPDRS Total scores were ≥27 (Upper Quartile population). Change from baseline in UPDRS scores were evaluated using mixed models repeated measures analyses. Of the 1578 patients randomized to the two studies, 1546 patients met criteria for inclusion in the meta-analysis. Effects on UPDRS Total, motor and activities of daily living scores were significantly better for both doses of rasagiline compared with placebo at all time periods. The Upper Quartile population included 402 patients with a UPDRS Total score ≥27 at baseline. These patients generally demonstrated a larger magnitude of treatment effect than was seen in the full population. This meta-analysis confirms the efficacy of rasagiline monotherapy over 36 weeks. Although TEMPO and ADAGIO are considered studies of "very early" PD, both contained a sizeable pool of patients with more severe disease. In addition, the meta-analysis showed a larger magnitude of effect in patients with more severe baseline disease.

  20. Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease.

    PubMed

    Backstrand, K H; Ng, A K; Takvorian, R W; Jones, E L; Fisher, D C; Molnar-Griffin, B J; Silver, B; Tarbell, N J; Mauch, P M

    2001-02-01

    To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.

  1. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease.

    PubMed

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T; Zaal, Kristien; Chandrasekharappa, Settara C; P Hanson, Eric; Yu, Zhen; Mullikin, James C; Hasni, Sarfaraz A; Wertz, Ingrid E; Ombrello, Amanda K; Stone, Deborah L; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K; Leavis, Helen L; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D; Gül, Ahmet; Siegel, Richard M; Boehm, Manfred; Milner, Joshua D; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M; Kastner, Daniel L; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-κB signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of IκBα and nuclear translocation of the NF-κB p65 subunit together with increased expression of NF-κB-mediated proinflammatory cytokines. A20 restricts NF-κB signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-κB-dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease.

  2. Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?

    PubMed

    Scott, Ian C; Rijsdijk, Frühling; Walker, Jemma; Quist, Jelmar; Spain, Sarah L; Tan, Rachael; Steer, Sophia; Okada, Yukinori; Raychaudhuri, Soumya; Cope, Andrew P; Lewis, Cathryn M

    2015-07-01

    Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA. We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions - for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models. HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24 months. HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

  3. Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

    2014-01-01

    Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

  4. Therapeutic singing as an early intervention for swallowing in persons with Parkinson's disease.

    PubMed

    Stegemöller, E L; Hibbing, P; Radig, H; Wingate, J

    2017-04-01

    For persons with Parkinson's disease (PD), secondary motor symptoms such as swallow impairment impact the quality of life and are major contributors to mortality. There is a present need for therapeutic interventions aimed at improving swallow function during the early stages of PD. The purpose of this pilot study was to examine the effects of a group therapeutic singing intervention on swallowing in persons with PD with no significant dysphagia symptoms. Cohort study. University in the United States. Twenty-four participants with PD. Eight weeks of group therapeutic singing. Electromyography (EMG) was used to assess muscle activity associated with swallow pre and post the group singing intervention. Swallow quality of life (SWAL-QOL) and the Unified Parkinson's Disease Rating Scale (UPDRS) were also obtained pre- and post-intervention. Participants reported minimal difficulty with swallowing, yet results revealed a significant increase in EMG outcome measures, as well as significant improvement in UPDRS total and UPDRS motor scores. No significant differences were revealed for SWAL-QOL. Increases in EMG timing measures may suggest that group singing results in the prolongation of laryngeal elevation, protecting the airway from foreign material for longer periods of time during swallow. Combined with the improvement in UPDRS clinical measures, therapeutic singing may be an engaging early intervention strategy to address oropharyngeal dysphagia while also benefiting additional clinical symptoms of PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

    PubMed

    Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

    2016-01-01

    Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost

  6. Mitochondrial metabolism in early neural fate and its relevance for neuronal disease modeling.

    PubMed

    Lorenz, Carmen; Prigione, Alessandro

    2017-12-01

    Modulation of energy metabolism is emerging as a key aspect associated with cell fate transition. The establishment of a correct metabolic program is particularly relevant for neural cells given their high bioenergetic requirements. Accordingly, diseases of the nervous system commonly involve mitochondrial impairment. Recent studies in animals and in neural derivatives of human pluripotent stem cells (PSCs) highlighted the importance of mitochondrial metabolism for neural fate decisions in health and disease. The mitochondria-based metabolic program of early neurogenesis suggests that PSC-derived neural stem cells (NSCs) may be used for modeling neurological disorders. Understanding how metabolic programming is orchestrated during neural commitment may provide important information for the development of therapies against conditions affecting neural functions, including aging and mitochondrial disorders. Copyright © 2017. Published by Elsevier Ltd.

  7. Investigations into Retinal Pathology in the Early Stages of a Mouse Model of Alzheimer’s Disease

    PubMed Central

    Chidlow, Glyn; Wood, John P.M.; Manavis, Jim; Finnie, John; Casson, Robert J.

    2016-01-01

    There is increasing recognition that visual performance is impaired in early stages of Alzheimer’s disease (AD); however, no consensus exists as to the mechanisms underlying this visual dysfunction, in particular regarding the timing, nature, and extent of retinal versus cortical pathology. If retinal pathology presents sufficiently early, it offers great potential as a source of novel biomarkers for disease diagnosis. The current project utilized an array of immunochemical and molecular tools to perform a characterization of retinal pathology in the early stages of disease progression using a well-validated mouse model of AD (APPSWE/PS1ΔE9). Analytical endpoints included examination of aberrant amyloid and tau in the retina, quantification of any neuronal degeneration, delineation of cellular stress responses of neurons and particularly glial cells, and investigation of oxidative stress. Brain, eyes, and optic nerves were taken from transgenic and wild-type mice of 3 to 12 months of age and processed for immunohistochemistry, qPCR, or western immunoblotting. The results revealed robust expression of the human APP transgene in the retinas of transgenic mice, but a lack of identifiable retinal pathology during the period when amyloid deposits were dramatically escalating in the brain. We were unable to demonstrate the presence of amyloid plaques, dystrophic neurites, neuronal loss, macro- or micro-gliosis, aberrant cell cycle re-entry, oxidative stress, tau hyperphosphorylation, or upregulations of proinflammatory cytokines or stress signaling molecules in the retina. The overall results do not support the hypothesis that detectable retinal pathology occurs concurrently with escalating amyloid deposition in the brains of APPSWE/PS1ΔE9 mice. PMID:28035930

  8. The Prevention of Early-Onset Neonatal Group B Streptococcal Disease.

    PubMed

    Money, Deborah; Allen, Victoria M

    2016-12-01

    To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal disease. The key revisions in this updated guideline include changed recommendations for regimens for antibiotic prophylaxis, susceptibility testing, and management of women with pre-labour rupture of membranes. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. Published literature was retrieved through searches of MEDLINE, CINAHL, and The Cochrane Library from January 1980 to July 2012 using appropriate controlled vocabulary and key words (group B streptococcus, antibiotic therapy, infection, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The recommendations in this guideline are designed to help clinicians identify and manage pregnancies at risk for neonatal group B streptococcal disease to optimize maternal and perinatal outcomes. No cost-benefit analysis is provided. There is good evidence based on randomized control trial data that in women with pre-labour rupture of membranes at term who are colonized with group B streptococcus, rates of neonatal infection are

  9. Are we giving azathioprine too late? The case for early immunomodulation in inflammatory bowel disease

    PubMed Central

    Etchevers, María Josefina; Aceituno, Montserrat; Sans, Miquel

    2008-01-01

    Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study). PMID:18810768

  10. Touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson's disease.

    PubMed

    Iakovakis, Dimitrios; Hadjidimitriou, Stelios; Charisis, Vasileios; Bostantzopoulou, Sevasti; Katsarou, Zoe; Hadjileontiadis, Leontios J

    2018-05-16

    Parkinson's disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients' quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject's status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.

  11. Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study.

    PubMed

    Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

    2012-04-01

    Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. To explore processes underpinning the implementation of CKD management in primary care. Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity.

  12. Detection of IFN-γ Secretion by T Cells Collected Before and After Successful Treatment of Early Lyme Disease.

    PubMed

    Callister, Steven M; Jobe, Dean A; Stuparic-Stancic, Aleksandra; Miyamasu, Misato; Boyle, Jeff; Dattwyler, Raymond J; Arnaboldi, Paul M

    2016-05-15

    Current serodiagnostics for Lyme disease lack sensitivity during early disease, and cannot determine treatment response. We evaluated an assay based on QuantiFERON technology utilizing peptide antigens derived from Borrelia burgdorferi to stimulate interferon-gamma (IFN-γ) release as an alternative to serodiagnosis for the laboratory detection of Lyme disease. Blood was obtained from patients with erythema migrans before (n = 29) and 2 months after (n = 27) antibiotic therapy. IFN-γ release was measured by enzyme-linked immunosorbent assay (ELISA) following overnight stimulation of whole blood with the peptide antigens, and compared to the results of standard serological assays (C6, ELISA, and Western blot). IFN-γ release was observed in pretreatment blood of 20 of 29 (69%) patients with Lyme disease. Following antibiotic treatment, IFN-γ was significantly reduced (P = .0002), and was detectable in only 4 of 20 (20%) initially positive patients. By contrast, anti-C6 antibodies were detected in pretreatment sera from 17 of 29 (59%) subjects, whereas only 5 of 29 (17%) patients had positive Western blot seroreactivity. Antibody responses persisted and expanded following treatment. Our findings suggest that measurement of IFN-γ after incubating blood with Borrelia antigens could be useful in the laboratory diagnosis of early Lyme disease. Also, after antibiotic treatment, this response appears to be short lived. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Early life nutrition, epigenetics and programming of later life disease.

    PubMed

    Vickers, Mark H

    2014-06-02

    The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be

  14. Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts: Space for Exploration

    NASA Technical Reports Server (NTRS)

    Elgart, S. R.; Little, M. P.; Campbell, L. J.; Milder, C. M.; Shavers, M. R.; Huff, J. L.; Patel, Z. S.

    2018-01-01

    Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to establish whether there is evidence for excess cardiovascular disease or cancer mortality in an early NASA astronaut cohort and determine if a correlation exists between space radiation exposure and mortality.

  15. Evaluation of Early Atherosclerosis Markers in Patients with Inflammatory Bowel Disease.

    PubMed

    Üstün, Yusuf; Kilincalp, Serta; Çoban, Şahin; Coşkun, Yusuf; Yüksel, İlhami; Ongun, Aydan; Soykan, İrfan; Bektaş, Mehmet; Törüner, Murat; Çetinkaya, Hülya; Örmeci, Necati

    2016-10-24

    BACKGROUND The aim of this study was to investigate relationships between early atherosclerosis and inflammatory bowel disease (IBD) using laboratory, functional, and morphological markers of atherosclerosis. MATERIAL AND METHODS In the present prospective single-center study, 96 patients with IBD (58 patients with ulcerative colitis and 36 patients with Crohn's disease) and 65 healthy control subjects were included. The demographic data of each patient and control subject were recorded. The patients with IBD and healthy controls were compared in terms of the carotid intima-media thickness (CIMT), the values of flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD), and the levels of von Willebrand factor antigen (VWF-Ag), D-dimer, and lipoprotein (a). RESULTS There were no significant differences between the IBD patients and controls in terms of age, sex, BMI, systolic and diastolic BPs, serum levels of total cholesterol, low-density lipoprotein, or triglycerides. IBD patients had significantly higher levels of VWF-Ag (156.6±58.9 vs. 104.2±43.3, P<0.001) and D-dimer (337.2±710.8 vs. 175.9±110.9, P<0.001) as compared to the controls. No significant differences were determined between the 2 groups in terms of FMD and NMD values. Although statistically not significant, the CIMT values were higher in the IBD patients than in the controls (0.517±0.141 mm vs. 0.467±0.099 mm, P=0.073). In the correlation analysis, the CIMT was found to be correlated negatively with FMD and positively with high sensitive C-reactive protein, VWF-Ag, and D-dimer. CONCLUSIONS These findings suggest that VWF-Ag and D-dimer can be beneficial early atherosclerosis markers in IBD patients.

  16. The Evolution of REM Sleep Behavior Disorder in Early Parkinson Disease

    PubMed Central

    Sixel-Döring, Friederike; Zimmermann, Johannes; Wegener, Andrea; Mollenhauer, Brit; Trenkwalder, Claudia

    2016-01-01

    Study Objectives: To investigate the development of REM sleep behavior disorder (RBD) and REM sleep behavioral events (RBE) not yet fulfilling diagnostic criteria for RBD as markers for neurodegeneration in a cohort of Parkinson disease (PD) patients between their de novo baseline assessment and two-year follow-up in comparison to healthy controls (HC). Methods: Clinically confirmed PD patients and HC with video-supported polysomnography (vPSG) data at baseline were re-investigated after two years. Diagnostic scoring for RBE and RBD was performed in both groups and related to baseline findings. Results: One hundred thirteen PD patients and 102 healthy controls (HC) were included in the study. Within two years, the overall occurrence of behaviors during REM sleep in PD patients increased from 50% to 63% (P = 0.02). RBD increased from 25% to 43% (P < 0.001). Eleven of 29 (38%) RBE positive PD patients and 10/56 (18%) patients with normal REM sleep at baseline converted to RBD. In HC, the occurrence of any REM behavior increased from 17% to 20% (n.s.). RBD increased from 2% to 4% (n.s.). One of 15 (7%) RBE positive HC and 1/85 (1%) HC with normal REM at baseline converted to RBD. Conclusions: RBD increased significantly in PD patients from the de novo state to two-year follow-up. We propose RBE being named “prodromal RBD” as it may follow a continuous evolution in PD possibly similar to the spreading of Lewy bodies in PD patients. RBD itself was shown as a robust and stable marker of early PD. Citation: Sixel-Döring F, Zimmermann J, Wegener A, Mollenhauer B, Trenkwalder C. The evolution of REM sleep behavior disorder in early Parkinson disease. SLEEP 2016;39(9):1737–1742. PMID:27306265

  17. Ultrasensitive sensor for detection of early stage chronic kidney disease in human.

    PubMed

    Desai, Dignya; Kumar, Ashok; Bose, Debajyoti; Datta, Manali

    2018-05-15

    A facile label free, ultrasensitive platform for a rapid detection of chronic kidney disease has been fabricated. Early intervention in patients with chronic kidney disease has the potential to delay, or even prevent, the development of end stage renal disease and complications, leading to a marked impact on life expectancy and quality of life. Thus, a potable electrochemical diagnostic biosensor has become an attractive option as electrochemical analysis is feasible to use for on-site detection of samples. In human, Cystatin C present in human body fluids is freely filtered by the glomerulus, but reabsorbed and catabolised by the renal tubules. Trace detectable amount is eliminated in urine, giving this molecular marker an edge over serum creatinine's disadvantages. A carboxyl functionalized multiwalled carbon nanotubes screen printed electrode was immobilized with papain (cysteine protease) where amino group of papain covalently bound carboxyl group on electrode surface by EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) and NHS (N-hydroxysuccinimide) chemistry. The modifications on sensor surface were characterized by field emission scanning electron microscopy. Interaction between papain and chronic kidney disease specific biomarker, Cystatin C was detected by cyclic voltammetry and differential pulse voltammetry within 10min. The sensor is highly specific to Cystatin C and showed negligible response to non-specific macromolecules present in urine. The sensitivity of the sensor was 1583.49µAcm -2 µg -1 and lower limit of detection of Cystatin C was found 0.58ngL -1 which presents as a promising platform for designing potable kidney disease detector. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn's disease.

    PubMed

    Safroneeva, E; Vavricka, S R; Fournier, N; Pittet, V; Peyrin-Biroulet, L; Straumann, A; Rogler, G; Schoepfer, A M

    2015-10-01

    The impact of early treatment with immunomodulators (IM) and/or TNF antagonists on bowel damage in Crohn's disease (CD) patients is unknown. To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2 years from the time of CD diagnosis. Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' with IM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio (HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery (HR 0.322, P = 0.005), and perianal surgery (HR 0.361, P = 0.042), as well as developing any complication (HR 0.567, P = 0.006). Treatment with immunomodulators or TNF antagonists within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2 years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication. © 2015 John Wiley & Sons Ltd.

  19. Modifications of the National Early Warning Score for patients with chronic respiratory disease.

    PubMed

    Pedersen, N E; Rasmussen, L S; Petersen, J A; Gerds, T A; Østergaard, D; Lippert, A

    2018-02-01

    The National Early Warning Score (NEWS) uses physiological variables to detect deterioration in hospitalized patients. However, patients with chronic respiratory disease may have abnormal variables not requiring interventions. We studied how the Capital Region of Denmark NEWS Override System (CROS), the Chronic Respiratory Early Warning Score (CREWS) and the Salford NEWS (S-NEWS) affected NEWS total scores and NEWS performance. In an observational study, we included patients with chronic respiratory disease. The frequency of use of CROS and the NEWS total score changes caused by CROS, CREWS and S-NEWS were described. NEWS, CROS, CREWS and S-NEWS were compared using 48-h mortality and intensive care unit (ICU) admission within 48 h as outcomes. We studied 11,266 patients during 25,978 admissions; the use of CROS lowered NEWS total scores in 40% of included patients. CROS, CREWS and S-NEWS had lower sensitivities than NEWS for 48-h mortality and ICU admission. Specificities and PPV were higher. CROS, CREWS and S-NEWS downgraded, respectively, 51.5%, 44.9% and 32.8% of the NEWS total scores from the 'mandatory doctor presence' and 'immediate doctor presence and specialist consultation' total score intervals to lower intervals. Capital Region of Denmark NEWS Override System was frequently used in patients with chronic respiratory disease. CROS, CREWS and S-NEWS reduced sensitivity for 48-h mortality and ICU admission. Using the methodology prevalent in the NEWS literature, we cannot conclude on the safety of these systems. Future prospective studies should investigate the balance between detection rate and alarm fatigue of different systems, or use controlled designs and patient-centred outcomes. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  20. Verbal Play as an Interactional Discourse Resource in Early Stage Alzheimer’s Disease

    PubMed Central

    Shune, Samantha; Duff, Melissa C.

    2012-01-01

    Background Verbal play, the creative and playful use of language to make puns, rhyme words, and tease, is a pervasive and enjoyable component of social communication and serves important interpersonal functions. The current study examines the use of verbal play in the communicative interactions of individuals with Alzheimer’s disease as part of a broader program of research on language-and-memory-in-use. Aims To document the frequency of verbal play in the communicative interactions of individuals with very mild Alzheimer’s disease (AD) and their familiar communication partners. To characterize the interactional forms, resources, and functions of playful episodes. Methods Using quantitative group comparisons and detailed discourse analysis, we analyzed verbal play in the interactional discourse of five participants with very mild AD and five healthy (demographically matched) comparison participants. Each participant interacted with a familiar partner while completing a collaborative referencing task, and with a researcher between task trials. Results A total of 1,098 verbal play episodes were coded. Despite being in the early stages of AD, all the AD participants used verbal play. There were no significant group differences in the frequency of verbal play episodes or in the interactional forms, resources, or functions of those playful episodes between AD and healthy comparison pair sessions. Conclusions The successful use of verbal play in the interactions of individuals with very mild AD and their partners highlights an area of preserved social communication. These findings represent an important step, both clinically and for research, in documenting the rich ways that individuals with early stage AD orchestrate interactionally meaningful communication with their partners through the use of interactional discourse resources like verbal play. This work also offers a promising clinical tool for tracking and targeting verbal play across disease progression. PMID

  1. Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.

    PubMed

    Stern, Matthew B; Marek, Kenneth L; Friedman, Joseph; Hauser, Robert A; LeWitt, Peter A; Tarsy, Daniel; Olanow, C Warren

    2004-08-01

    Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P < 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD. Copyright 2004 Movement Disorder Society

  2. No sex differences in use of dopaminergic medication in early Parkinson disease in the US and Canada - baseline findings of a multicenter trial.

    PubMed

    Umeh, Chizoba C; Pérez, Adriana; Augustine, Erika F; Dhall, Rohit; Dewey, Richard B; Mari, Zoltan; Simon, David K; Wills, Anne-Marie A; Christine, Chadwick W; Schneider, Jay S; Suchowersky, Oksana

    2014-01-01

    Sex differences in Parkinson disease clinical features have been reported, but few studies have examined sex influences on use of dopaminergic medication in early Parkinson disease. The objective of this study was to test if there are differences in the type of dopaminergic medication used and levodopa equivalent daily dose between men and women with early Parkinson disease enrolled in a large multicenter study of Creatine as a potential disease modifying therapy - the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease Long-Term Study-1. Baseline data of 1,741 participants from 45 participating sites were analyzed. Participants from the United States and Canada were enrolled within five years of Parkinson Disease diagnosis. Two outcome variables were studied: type of dopaminergic medication used and levodopa equivalent daily dose at baseline in the Long-Term Study-1. Chi-square statistic and linear regression models were used for statistical analysis. There were no statistically significant differences in the frequency of use of different types of dopaminergic medications at baseline between men and women with Parkinson Disease. A small but statistically significant difference was observed in the median unadjusted levodopa equivalent daily dose at baseline between women (300 mg) and men (325 mg), but this was not observed after controlling for disease duration (years since Parkinson disease diagnosis), disease severity (Unified Parkinson's Disease Rating Scale Motor and Activities of Daily Living Scores), and body weight. In this large multicenter study, we did not observe sex differences in the type and dose of dopaminergic medications used in early Parkinson Disease. Further research is needed to evaluate the influence of male or female sex on use of dopaminergic medication in mid- and late-stage Parkinson Disease.

  3. Use of multimodality imaging and artificial intelligence for diagnosis and prognosis of early stages of Alzheimer's disease.

    PubMed

    Liu, Xiaonan; Chen, Kewei; Wu, Teresa; Weidman, David; Lure, Fleming; Li, Jing

    2018-04-01

    Alzheimer's disease (AD) is a major neurodegenerative disease and the most common cause of dementia. Currently, no treatment exists to slow down or stop the progression of AD. There is converging belief that disease-modifying treatments should focus on early stages of the disease, that is, the mild cognitive impairment (MCI) and preclinical stages. Making a diagnosis of AD and offering a prognosis (likelihood of converting to AD) at these early stages are challenging tasks but possible with the help of multimodality imaging, such as magnetic resonance imaging (MRI), fluorodeoxyglucose (FDG)-positron emission topography (PET), amyloid-PET, and recently introduced tau-PET, which provides different but complementary information. This article is a focused review of existing research in the recent decade that used statistical machine learning and artificial intelligence methods to perform quantitative analysis of multimodality image data for diagnosis and prognosis of AD at the MCI or preclinical stages. We review the existing work in 3 subareas: diagnosis, prognosis, and methods for handling modality-wise missing data-a commonly encountered problem when using multimodality imaging for prediction or classification. Factors contributing to missing data include lack of imaging equipment, cost, difficulty of obtaining patient consent, and patient drop-off (in longitudinal studies). Finally, we summarize our major findings and provide some recommendations for potential future research directions. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.

    PubMed

    Marques, Adriana; Schwartz, Ira; Wormser, Gary P; Wang, Yanmei; Hornung, Ronald L; Demirkale, Cumhur Y; Munson, Peter J; Turk, Siu-Ping; Williams, Carla; Lee, Chyi-Chia Richard; Yang, Jun; Petzke, Mary M

    2017-12-27

    The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells. This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  5. TGF-β mediates early angiogenesis and latent fibrosis in an Emilin1-deficient mouse model of aortic valve disease

    PubMed Central

    Munjal, Charu; Opoka, Amy M.; Osinska, Hanna; James, Jeanne F.; Bressan, Giorgio M.; Hinton, Robert B.

    2014-01-01

    Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF), fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein that regulates elastogenesis and inhibits TGF-β signaling, but the role of Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1 deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β dysregulation. Using histology, immunohistochemistry, electron microscopy, quantitative gene expression analysis, immunoblotting and echocardiography, we examined the effects of Emilin1 deficiency (Emilin1−/−) in mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell-matrix defects in aortic valve tissue, including EFF, that progress to latent AVD and premature death. The Emilin1−/− aortic valve displays early aberrant provisional angiogenesis and late neovascularization. In addition, Emilin1−/− aortic valves are characterized by early valve interstitial cell activation and proliferation and late myofibroblast-like cell activation and fibrosis. Interestingly, canonical TGF-β signaling (phosphorylated Smad2 and Smad3) is upregulated constitutively from birth to senescence, whereas non-canonical TGF-β signaling (phosphorylated Erk1 and Erk2) progressively increases over time. Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β activation. The early manifestation of EFF and aberrant angiogenesis suggests that these processes are crucial intermediate factors involved in disease progression and therefore might provide new therapeutic targets for human AVD. PMID:25056700

  6. Effects of Phosphate Binder Therapy on Vascular Stiffness in Early Stage Chronic Kidney Disease

    PubMed Central

    Seifert, Michael E.; de las Fuentes, Lisa; Rothstein, Marcos; Dietzen, Dennis J.; Bierhals, Andrew J.; Cheng, Steven C.; Ross, Will; Windus, David; Dávila-Román, Víctor G.; Hruska, Keith A.

    2013-01-01

    Background/Aims Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). The CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of the CKD-MBD. Methods We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23 (FGF23), Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2–3-fold at baseline but were not affected by LaCO3. Conclusion 12 months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of the CKD-MBD. PMID:23941761

  7. [The early diagnosis value of EV 71 IgM class antibodies in the hand, foot and mouth disease].

    PubMed

    Zhao, Jing; Xu, Jun; Chen, Wei-wei; Li, Yong-li; Tang, Yan; Li, Jia; Wang, Hai-bin; Guo, Tong-sheng; Zhao, Min; Li, Bo-an; Mao, Yuan-li

    2011-04-01

    Assessment of detection of IgM antibodies for human enterovirus 71 (EV 71) in early diagnosis for the hand, foot and mouth disease (HFMD). The sera and throat swabs from 38 patients which were clinical diagnosis as HFMD, were continuous daily collected in our hospital in 2010. These specimens were detected by EV 71 IgM antibodies assay, real time RT-PCR methods for EV 71 and Enterovirus. Among 38 HFMD patients, the cumulative positive rates of EV 71 IgM antibodies were: 60.5% on day 1, 71.1% on day 2, 81.5% in the first 3-4 days, 92.1% on day 5, 92.1% on day 6, and the positive rate of nucleic acid detected by the real time RT-PCR for EV 71 and Enterovirus were 60.5%, 73.6%. The positive rate of EV 71 IgM antibodies in the hand, foot and mouth disease just can occur on day 1, and reach to peak on day 5, which can be used as one of indicators of early diagnosis of hand, foot and mouth disease.

  8. The role of the striatum in rule application: the model of Huntington's disease at early stage.

    PubMed

    Teichmann, Marc; Dupoux, Emmanuel; Kouider, Sid; Brugières, Pierre; Boissé, Marie-Françoise; Baudic, Sophie; Cesaro, Pierre; Peschanski, Marc; Bachoud-Lévi, Anne-Catherine

    2005-05-01

    The role of the basal ganglia, and more specifically of the striatum, in language is still debated. Recent studies have proposed that linguistic abilities involve two distinct types of processes: the retrieving of stored information, implicating temporal lobe areas, and the application of combinatorial rules, implicating fronto-striatal circuits. Studies of patients with focal lesions and neurodegenerative diseases have suggested a role for the striatum in morphological rule application, but functional imaging studies found that the left caudate was involved in syntactic processing and not morphological processing. In the present study, we tested the view that the basal ganglia are involved in rule application and not in lexical retrieving in a model of striatal dysfunction, namely Huntington's disease at early stages. We assessed the rule-lexicon dichotomy in the linguistic domain with morphology (conjugation of non-verbs and verbs) and syntax (sentence comprehension) and in a non-linguistic domain with arithmetic operations (subtraction and multiplication). Thirty Huntington's disease patients (15 at stage I and 15 at stage II) and 20 controls matched for their age and cultural level were included in this study. Huntington's disease patients were also assessed using the Unified Huntington's Disease Rating Scale (UHDRS) and MRI. We found that early Huntington's disease patients were impaired in rule application in the linguistic and non-linguistic domains (morphology, syntax and subtraction), whereas they were broadly spared with lexical processing. The pattern of performance was similar in patients at stage I and stage II, except that stage II patients were more impaired in all tasks assessing rules and had in addition a very slight impairment in the lexical condition of conjugation. Finally, syntactic rule abilities correlated with all markers of the disease evolution including bicaudate ratio and performance in executive function, whereas there was no

  9. [Usefulness of serological studies for the early diagnosis of Lyme disease in Primary Health Care Centres].

    PubMed

    Vázquez-López, María Esther; Fernández, Gonzalo; Díaz, Pablo; Díez-Morrondo, Carolina; Pego-Reigosa, Robustiano; Coira-Nieto, Amparo

    2018-01-01

    The main aim of this study was to determine the usefulness of an early diagnosis of Lyme disease (LD) in Primary Health Care Centres (PHCC) using the ELISA test as serological screening technique. A retrospective study (2006-2013) was performed in order to determine the anti-Borrelia seropositivity in 2,842 people at risk of having LD. The possible relationship between the environment and the area of residence with anti-Borrelia seropositivity was also studied according to the origin of the specimens (PHCC/Hospital). Overall, 15.2% of samples were positive to Borrelia spp. Seropositivity was significantly higher in samples sent by PHCC doctors than those sent by Hospital doctors. Seropositivity was significantly higher in rural than in urban populations and in those who live in mountainous or flat areas. The percentage of seropositivity has increased over the years. The role of the PHCC doctor is essential for achieving an early diagnosis of Lyme disease, as a higher percentage of seropositives was detected in samples submitted from PHCC. Furthermore, most early localised LD patients were diagnosed in PHCC, avoiding the appearance of sequelae. Therefore, detection of Borrelia specific antibodies using an ELISA assay is a useful screening test for patients at risk of LD. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  10. Hereditary Parkinson s Disease Natural History Protocol

    ClinicalTrials.gov

    2018-03-27

    Parkinson Disease 6, Early-Onset; Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human; Parkinson Disease Autosomal Recessive, Early Onset; Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1

  11. Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

    PubMed

    Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

    2017-10-01

    Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  12. The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies.

    PubMed

    Alduraywish, S A; Lodge, C J; Campbell, B; Allen, K J; Erbas, B; Lowe, A J; Dharmage, S C

    2016-01-01

    There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years. Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. GP-delivered secondary prevention cardiovascular disease programme; early predictors of likelihood of patient non-adherence.

    PubMed

    Fitzpatrick, Patricia; Lonergan, Moira; Collins, Claire; Daly, Leslie

    2010-12-01

    The aim of this study was to determine how routinely recorded data could predict early the likelihood of patient non-adherence to a primary care-delivered secondary prevention programme for established coronary heart disease (CHD), with patients with CHD (10,851) invited to attend four times per year. Non-adherence was defined as attending no more than three GP visits ever. The study sample was selected to allow a possible two-year recorded follow-up period in which patients could take up invitations. Administrative recordings of visit dates and intervals between visits, baseline results of key parameters and early changes were examined using logistic regression to determine independent predictors of non-adherence. Longer interval between early visits, no family history of CHD, smoking and being outside target for exercise at baseline were independently associated with non-adherence. Early identification by GPs of those who fail to attend on time or who defer appointments, in addition to persistence of lifestyle factors unchanged by a prior serious cardiac event should serve as a warning sign that targeted interventions to maintain adherence in primary care-delivered secondary prevention programmes are necessary.

  14. Fungal infections in children in the early postoperative period after cardiac surgery for congenital heart disease: a single-centre experience.

    PubMed

    Jaworski, Radoslaw; Haponiuk, Ireneusz; Irga-Jaworska, Ninela; Chojnicki, Maciej; Steffens, Mariusz; Paczkowski, Konrad; Zielinski, Jacek

    2016-09-01

    Postoperative infections are still an important problem in cardiac surgery, especially in the paediatric population, and may influence the final outcome of congenital heart disease treatment. Postoperative infections with fungi are uncommon. The aetiology is poorly understood, and the proper diagnosis and treatment is unclear. In this single-centre study, the frequency of invasive fungal disease in children who underwent surgical management of congenital heart diseases was determined along with the risk factors for infection, treatment options and outcomes. All consecutive paediatric patients (<18 years of age) who underwent cardiac surgery for congenital heart disease between September 2008 and December 2015 in a paediatric cardiac centre in Poland were identified. Those who developed invasive fungal disease in the early postoperative period (30 days) were identified. Of the 1540 cardiosurgical procedures for congenital heart disease, 6 were complicated by fungal infection (0.39%). One patient had a high probability of fungal infection, but the diagnosis was unproved. Nevertheless, the patient was successfully treated with antifungal treatment. Five had proven invasive fungal disease. Of these, 3 were diagnosed with candidaemia. All had undergone cardiopulmonary bypass. Of the remaining 2 patients, 1 was a preterm newborn with complete atrioventricular septal defect who developed rib fungal invasion. The remaining patient had pulmonary atresia with ventricular septal defect and developed Fournier's gangrene after surgery. None of the patients died due to infection in the early postoperative period. However, the child with rib fungal invasion died 39 days after surgery as a result of multiorgan failure. Fungal infections in paediatric patients after cardiac surgery may markedly influence morbidity and mortality. Fungal infection prophylaxis in this specific group of children may reduce morbidity, whereas early empirical treatment followed by a targeted approach may

  15. Selective alterations of neurons and circuits related to early memory loss in Alzheimer’s disease

    PubMed Central

    Llorens-Martín, Maria; Blazquez-Llorca, Lidia; Benavides-Piccione, Ruth; Rabano, Alberto; Hernandez, Felix; Avila, Jesus; DeFelipe, Javier

    2014-01-01

    A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII → dentate gyrus → CA3 → CA1) and monosynaptic (ECIII → CA1) circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits. PMID:24904307

  16. Gold-mercaptopropionic acid-polyethylenimine composite based DNA sensor for early detection of rheumatic heart disease.

    PubMed

    Singh, Swati; Kaushal, Ankur; Khare, Shashi; Kumar, Pradeep; Kumar, Ashok

    2014-07-21

    The first gold-mercaptopropionic acid-polyethylenimine composite based electrochemical DNA biosensor was fabricated for the early detection of Streptococcus pyogenes infection in humans causing rheumatic heart disease (heart valve damage). No biosensor is available for the detection of rheumatic heart disease (RHD). Therefore, the mga gene based sensor was developed by the covalent immobilization of a 5'-carboxyl modified single stranded DNA probe onto the gold composite electrode. The immobilized probe was hybridized with the genomic DNA (G-DNA) of S. pyogenes from throat swabs and the electrochemical response was measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance (EI). Covalent immobilization of the probe onto the gold composite and its hybridization with G-DNA was characterized by FTIR and SEM. The sensitivity of the sensor was 110.25 μA cm(-2) ng(-1) with DPV and the lower limit of detection was 10 pg per 6 μL. The sensor was validated with patient throat swab samples and results were compared with available methods. The sensor is highly specific to S. pyogenes and can prevent damage to heart valves by the early detection of the infection in only 30 min.

  17. Children's, parents' and other stakeholders' perspectives on early dietary self-management to delay disease progression of chronic disease in children: a protocol for a mixed studies systematic review with a narrative synthesis.

    PubMed

    Pugh, Pearl; Hemingway, Pippa; Christian, Martin; Higginbottom, Gina

    2018-01-25

    Chronic disease of childhood may be delayed by early dietary intervention. The purpose of this systematic review is to provide decision-makers with a perspective on the role of early dietary intervention, as a form of self-management, to delay disease progression in children with early chronic disease, as described by children, parents and other stakeholders. The study will systematically review empirical research (qualitative, quantitative and mixed method designs), including grey literature, using a narrative synthesis. A four-stage search process will be conducted involving a scoping search, the Scottish Intercollegiate Guidelines Network (SIGN) Patient Issues search filter on MEDLINE, the search of seven databases using a chronic disease and chronic kidney disease (CKD) search strategy, and hand searching the reference lists of identified papers for additional studies. All studies retrieved during the search process will undergo a screening and selection process against the inclusion/exclusion criteria. Methodological quality of relevant studies will be assessed using a validated Mixed Studies Review scoring system, before inclusion in the review. Relevant grey literature will be assessed for methodological quality and relative importance using McGrath et al.'s framework and the Academy Health advisory committee categories, respectively. Data extraction will be guided by the Centre for Review and Dissemination guidance and Popay et al.'s work. The narrative synthesis of the findings will use elements of Popay et al.'s methodology of narrative synthesis, applying recognised tools for each of the four elements: (1) developing a theory of how the intervention works, why and for whom; (2) developing a preliminary synthesis of findings of included studies; (3) exploring relationships in the data; and (4) assessing the robustness of the synthesis. This mixed studies systematic review with a narrative synthesis seeks to elucidate the gaps in current knowledge and

  18. Language background in early life may be related to neuropsychiatry symptoms in patients with Alzheimer disease.

    PubMed

    Liu, Yi-Chien; Hsu, Jung-Lung; Wang, Shuu-Jin; Yip, Ping-Keung; Meguro, Kenichi; Fuh, Jong-Ling

    2017-02-10

    The relationship between early life experience and the occurrence of neuropsychiatry symptoms (NPSs) in patients with Alzheimer disease (AD) is unclear. From 2012 to 2014, we prospectively recruited 250 patients with probable AD from the memory clinic of Taipei Veterans General Hospital. All patients underwent standard assessments, including brain magnetic resonance imaging or computed tomography, neuropsychological tests, neuropsychiatry inventory (NPI-Q) and related blood tests. A linear regression analysis was performed to investigate the relationship between NPSs and age, gender, disease severity, depression, language background (with or without Japanese education). Among the 250 participants, 113 (45.2%) were women. Their average age was 82.6 years. Of all the participants, 93 (37.2%) had received formal Japanese education, whereas 157 (62.8%) did not receive Japanese education. The participants with Japanese education were slightly younger (83.1 ± 3.6 vs. 81.4 ± 3.4, P = 0.006), with a higher proportion of them were women (30.5% vs. 69.8%, P < 0.001) and fewer years of total education (10.8 ± 4.5 vs. 7.7 ± 3.2, P < 0.001), compared to the participants without Japanese education. NPI-Q scores significantly differed between the two groups (15.8 vs. 24.1, P = 0.024). Both disease severity and language background predicted NPI-Q scores. Language background in early life may be related to NPSs in patients with AD, and this effect is more significant in patients with a lower education level than in those with a higher education level. More NPSs may be the result of negative effects on dominant language or early life experiences.

  19. A comparison of sumanirole versus placebo or ropinirole for the treatment of patients with early Parkinson's disease.

    PubMed

    Singer, Carlos; Lamb, Janice; Ellis, Amanda; Layton, Gary

    2007-03-15

    To assess the safety and efficacy of sumanirole, a highly selective dopamine agonist, versus placebo and demonstrate its noninferiority to ropinirole, 614 patients with early Parkinson's disease (PD) were treated with sumanirole, 1 to 16 mg/day; ropinirole, 0.75 to 24 mg/day; or placebo. Primary end point in this flexible-dose, double-blind, double-dummy, parallel-group study of 40 weeks was the change in total sum of the United Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores from baseline to end of maintenance. Approximately half the subjects in the sumanirole and placebo groups withdrew early from the study, most (51.8% and 68.5%, respectively) due to lack of efficacy. Of the ropinirole subjects who withdrew (50.5%), most discontinued because of adverse events. In sumanirole and ropinirole groups, mean changes from baseline of -2.48 and -5.20 in UPDRS II + III mean scores were significant versus 0.38 in the placebo group (P early PD when compared with placebo. Noninferiority of sumanirole to ropinirole was not demonstrated, with a difference of 2.70 (90% CI, 0.92-4.49). Sumanirole was better tolerated than ropinirole. (c) 2006 Movement Disorder Society.

  20. Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease

    PubMed Central

    Macías-Segura, N.; Bastian, Y.; Santiago-Algarra, D.; Castillo-Ortiz, J. D.; Alemán-Navarro, A. L.; Jaime-Sánchez, E.; Gomez-Moreno, M.; Saucedo-Toral, C. A.; Lara-Ramírez, Edgar E.; Zapata-Zuñiga, M.; Enciso-Moreno, L.; González-Amaro, R.; Ramos-Remus, C.; Enciso-Moreno, J. A.

    2018-01-01

    Background Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. Methods Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. Results A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. Conclusion The presence of a specific transcriptome in whole blood of RA patients suggests the activation

  1. Motor-cognitive dual-task deficits in individuals with early-mid stage Huntington disease.

    PubMed

    Fritz, Nora E; Hamana, Katy; Kelson, Mark; Rosser, Anne; Busse, Monica; Quinn, Lori

    2016-09-01

    Huntington disease (HD) results in a range of cognitive and motor impairments that progress throughout the disease stages; however, little research has evaluated specific dual-task abilities in this population, and the degree to which they may be related to functional ability. The purpose of this study was to a) examine simple and complex motor-cognitive dual-task performance in individuals with HD, b) determine relationships between dual-task walking ability and disease-specific measures of motor, cognitive and functional ability, and c) examine the relationship of dual-task measures to falls in individuals with HD. Thirty-two individuals with HD were evaluated for simple and complex dual-task ability using the Walking While Talking Test. Demographics and disease-specific measures of motor, cognitive and functional ability were also obtained. Individuals with HD had impairments in simple and complex dual-task ability. Simple dual-task walking was correlated to disease-specific motor scores as well as cognitive performance, but complex dual-task walking was correlated with total functional capacity, as well as a range of cognitive measures. Number of prospective falls was moderately-strongly correlated to dual-task measures. Our results suggest that individuals with HD have impairments in cognitive-motor dual-task ability that are related to disease progression and specifically functional ability. Dual-task measures appear to evaluate a unique construct in individuals with early to mid-stage HD, and may have value in improving the prediction of falls risk in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

    PubMed

    Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

    2017-02-07

    In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Gender's Effects to the Early Symptoms of Alzheimer's Disease in 5 Asian Countries.

    PubMed

    Yang, Yuan-Han; Meguro, Kenichi; Dominguez, Jacqueline; Chen, Christopher Li-Hsian; Wang, Huali; Ong, Paulus Anam

    2017-06-01

    Asia has the greatest population and more patients with dementia in the world. Early recognition of clinical symptoms of Alzheimer's disease (AD) is crucial for dementia care. In order to foster collaboration in AD care, a uniformed manner to report the early clinical symptoms of AD is necessary. We have recruited clinically diagnosed patients with AD at their very mild stage with Clinical Dementia Rating (CDR) 0.5 in Taiwan, Japan, China, Philippines, and Singapore. Demographic characteristics and psychometrics including Ascertain of Dementia-8 (AD8) questionnaire were administrated to collect and report the clinical presentation in these countries. In total, 713 clinically diagnosed patients with AD at very mild stage, CDR 0.5, have been recruited from these 5 countries. "Repeats questions, stories, or statements" were consistently the frequently reported symptom across these countries. Taiwan, China, and Singapore have the higher AD8 total score compared to that in Japan and Philippines. Japan and Philippines have the gender-related differences in clinical presentation of early AD. Difficulties in using small trouble appliance and in handling complicated financial affairs were frequently reported in Japan female, compared to male, patients with AD. Identifying the clinical symptom of AD and the gender-related issues would be crucial in the dementia care in Asia.

  4. Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

    PubMed

    Charles, James A; Peterlin, B L; Rapoport, Alan M; Linder, Steven L; Kabbouche, Marielle A; Sheftell, Fred D

    2009-08-01

    There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease.

  5. Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice.

    PubMed

    Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Sly, Peter D; Larcombe, Alexander N

    2016-01-01

    Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.

  6. Perfusion MRI in Early Stage of Legg-Calvé-Perthes Disease to Predict Lateral Pillar Involvement: A Preliminary Study.

    PubMed

    Kim, Harry K W; Wiesman, Kathryn D; Kulkarni, Vedant; Burgess, Jamie; Chen, Elena; Brabham, Case; Ikram, Haseeb; Du, Jerry; Lu, Amanda; Kulkarni, Ashok V; Dempsey, Molly; Herring, J Anthony

    2014-07-16

    Current radiographic classifications for Legg-Calvé-Perthes disease cannot be applied at the early stages of the disease. The purpose of this study was to quantify the perfusion of the femoral epiphysis in the early stages of Legg-Calvé-Perthes disease with use of perfusion magnetic resonance imaging (MRI) and to determine if the extent of epiphyseal perfusion can predict the lateral pillar involvement at the mid-fragmentation stage. Twenty-nine patients had gadolinium-enhanced perfusion MRI at the initial stage or early fragmentation stage of Legg-Calvé-Perthes disease and were followed prospectively. The percent perfusion of the whole epiphysis and its lateral third was measured by four independent observers using image analysis software. The radiographs obtained at the mid-fragmentation stage were used for the lateral pillar classification. Intraclass correlation coefficient (ICC) and logistic regression analyses were performed. The mean age (and standard deviation) at diagnosis was 7.7 ± 1.7 years (range, 5.3 to 11.3 years). The mean interval between the MRI and the time of maximum fragmentation was 8.2 ± 5.5 months. The interobserver ICC for the percent perfusion of the lateral third of the epiphysis was 0.90 (95% confidence interval [CI]: 0.83 to 0.95). The mean percent perfusion of the lateral third of the epiphysis was 92% ± 2%, 68% ± 18%, and 46% ± 12% for the hips in which the lateral pillar was later classified as A, B, and C, respectively (p = 0.001). When the perfusion level was ≥90% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group A, as opposed to B or C, was 72.0 (CI: 3.5 to 1476). With a perfusion level of ≤55% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group C, as opposed to A or B, was 33.3 (CI: 2.8 to 392). Similar results were obtained for the whole epiphysis. Perfusion MRI measurements of the total epiphysis and its

  7. Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

    2012-01-01

    Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

  8. Heterozygous familial hypercholesterolemia: an underrecognized cause of early cardiovascular disease.

    PubMed

    Yuan, George; Wang, Jian; Hegele, Robert A

    2006-04-11

    Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder that affects about 1 in 500 people, with a higher prevalence in certain subpopulations such as people of Quebecois, Christian Lebanese and Dutch South Afrikaner extraction. HeFH is characterized by cholesterol deposits affecting the corneas, eyelids and extensor tendons; elevated plasma concentrations of low-density lipoprotein (LDL) cholesterol; and accelerated vascular disease, especially coronary artery disease (CAD). Although HeFH is genetically heterogeneous, it is most often caused by heterozygous mutations in the LDLR gene encoding the LDL receptor. We describe a man who was diagnosed with HeFH after he had a myocardial infarction at 33 years of age. By DNA sequence analysis, he was found to have a heterozygous splicing mutation in his LDLR gene. This discovery expanded the growing mutational spectrum in patients with HeFH in Ontario. Given that HeFH is a treatable cause of early vascular disease, it is important that this condition be recognized, diagnosed and treated in affected patients; but as yet, there is no consensus on the best approach. Diagnostic criteria based on family history and clinical presentation have been proposed for patients with suspected HeFH. Biochemical or molecular screening might be considered to detect new cases of HeFH in populations with a relatively high HeFH prevalence and a relatively small number of possible causative mutations. So far, however, the most cost-effective and efficient systematic strategy to detect previously undiagnosed cases of HeFH is still cascade testing: clinical and biochemical screening of close relatives of the proband patient diagnosed with HeFH. Pharmacologic treatment of HeFH is cost-effective.

  9. Heterozygous familial hypercholesterolemia: an underrecognized cause of early cardiovascular disease

    PubMed Central

    Yuan, George; Wang, Jian; Hegele, Robert A.

    2006-01-01

    Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder that affects about 1 in 500 people, with a higher prevalence in certain subpopulations such as people of Quebecois, Christian Lebanese and Dutch South Afrikaner extraction. HeFH is characterized by cholesterol deposits affecting the corneas, eyelids and extensor tendons; elevated plasma concentrations of low-density lipoprotein (LDL) cholesterol; and accelerated vascular disease, especially coronary artery disease (CAD). Although HeFH is genetically heterogeneous, it is most often caused by heterozygous mutations in the LDLR gene encoding the LDL receptor. We describe a man who was diagnosed with HeFH after he had a myocardial infarction at 33 years of age. By DNA sequence analysis, he was found to have a heterozygous splicing mutation in his LDLR gene. This discovery expanded the growing mutational spectrum in patients with HeFH in Ontario. Given that HeFH is a treatable cause of early vascular disease, it is important that this condition be recognized, diagnosed and treated in affected patients; but as yet, there is no consensus on the best approach. Diagnostic criteria based on family history and clinical presentation have been proposed for patients with suspected HeFH. Biochemical or molecular screening might be considered to detect new cases of HeFH in populations with a relatively high HeFH prevalence and a relatively small number of possible causative mutations. So far, however, the most cost-effective and efficient systematic strategy to detect previously undiagnosed cases of HeFH is still cascade testing: clinical and biochemical screening of close relatives of the proband patient diagnosed with HeFH. Pharmacologic treatment of HeFH is cost-effective. PMID:16606962

  10. Early- and late-onset Alzheimer disease: Are they the same entity?

    PubMed

    Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

    2018-05-01

    Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Retinal vascular imaging in early life: insights into processes and risk of cardiovascular disease

    PubMed Central

    Li, Ling‐Jun; Ikram, Mohammad Kamran

    2015-01-01

    Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent years, studies have shown that the origins of CVD may be traced to vascular and metabolic processes in early life. Retinal vascular imaging is a new technology that allows detailed non‐invasive in vivo assessment and monitoring of the microvasculature. In this systematic review, we described the application of retinal vascular imaging in children and adolescents, and we examined the use of retinal vascular imaging in understanding CVD risk in early life. We reviewed all publications with quantitative retinal vascular assessment in two databases: PubMed and Scopus. Early life CVD risk factors were classified into four groups: birth risk factors, environmental risk factors, systemic risk factors and conditions linked to future CVD development. Retinal vascular changes were associated with lower birth weight, shorter gestational age, low‐fibre and high‐sugar diet, lesser physical activity, parental hypertension history, childhood hypertension, childhood overweight/obesity, childhood depression/anxiety and childhood type 1 diabetes mellitus. In summary, there is increasing evidence supporting the view that structural changes in the retinal microvasculature are associated with CVD risk factors in early life. Thus, the retina is a useful site for pre‐clinical assessment of microvascular processes that may underlie the future development of CVD in adulthood. PMID:26435039

  12. Early life exposure to permethrin: a progressive animal model of Parkinson's disease.

    PubMed

    Nasuti, Cinzia; Brunori, Gloria; Eusepi, Piera; Marinelli, Lisa; Ciccocioppo, Roberto; Gabbianelli, Rosita

    Oxidative stress, alpha-synuclein changes, mitochondrial complex I defects and dopamine loss, observed in the striatum of rats exposed to the pesticide permethrin in early life, could represent neuropathological hallmarks of Parkinson's disease (PD). Nevertheless, an animal model of PD should also fulfill criteria of face and predictive validities. This study was designed to: 1) verify dopaminergic status in the striatum and substantia nigra pars compacta; 2) recognize non-motor symptoms; 3) investigate the time-course development of motor disabilities; 4) assess L-Dopa effectiveness on motor symptoms in rats previously exposed to permethrin in early life. The permethrin-treated group received 34mg/kg daily of permethrin from postnatal day 6 to 21, whereas the age-matched control group was administered with the vehicle only. At adolescent age, the permethrin-treated group showed decreased levels of dopamine in the striatum, loss of dopaminergic neurons in the substantia nigra pars compacta and cognitive impairments. Motor coordination defects appeared at adult age (150days old) in permethrin-treated rats on rotarod and beam walking tasks, whereas no differences between the treated and control groups were detected on the foot print task. Predictive validity was evaluated by testing the ability of L-Dopa (5, 10 or 15mg/kg, os) to restore the postural instability in permethrin-treated rats (150days old) tested in a beam walking task. The results revealed full reversal of motor deficits starting from 10mg/kg of L-Dopa. The overall results indicate that this animal model replicates the progressive, time-dependent nature of the neurodegenerative process in Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Early detection of probable idiopathic Parkinson's disease: I. development of a diagnostic test battery.

    PubMed

    Montgomery, Erwin B; Koller, William C; LaMantia, Theodora J K; Newman, Mary C; Swanson-Hyland, Elizabeth; Kaszniak, Alfred W; Lyons, Kelly

    2000-05-01

    We developed a test battery as an inexpensive and objective aid for the early diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses. The test battery incorporates tests of motor function, olfaction, and mood. In the motor task, a wrist flexion-and-extension task to different targets, movement velocities were recorded. Olfaction was tested with the University of Pennsylvania Smell Identification Test. Mood was assessed with the Beck Depression Inventory. An initial regression model was developed from the results of 19 normal control subjects and 18 patients with early, mild, probable iPD. Prospective application to an independent validation set of 122 normal control subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity rate, with an area under the Receiver Operator Characteristic curve of 0.87. Copyright © 2000 Movement Disorder Society.

  14. Analysis of iodine-131-induced early thyroid hormone variations in Graves' disease.

    PubMed

    Xu, Feng; Gu, Aichun; Pan, Yifan; Yang, Liwen; Ma, Yubo

    2016-11-01

    This prospective study aimed to assess iodine-131 (I)-induced early thyroid hormone variations in Graves' disease (GD) and determine the associated factors. One hundred and seventy-one GD patients treated with I were evaluated (47 men, 124 women). I was administered at 9.0±4.9 mCi on average. Serum free triiodothyronine and free thyroxin were measured within 24 h before treatment and 8 (3-14) days after treatment. Patients were divided into increase, no change, and decrease groups, respectively, on the basis of hormone variations after treatment. χ-Test, analysis of variance, and the Kruskal-Wallis test were used to compare groups in terms of sex, age, course of disease, thyroid stimulating hormone receptor antibodies, antithyroid drug (ATD) pretreatment time, time of ATD discontinuation before I treatment, 24 h thyroid I uptake, thyroid weight, I activity, and I activity/thyroid weight (μCi/g). The Spearman method was used for correlation analyses. Twenty-seven, 20, and 124 cases were assigned to increase, no change, and decrease groups, respectively. Significant differences were found among groups in the time of ATD discontinuation before I treatment [the median duration for methimazole was 11 (5-26), 16 (10-30), and 21 (1-30) days, P=0.000, the median duration for propylthiouracil was 12.5 (5-24), 22 (11-26), and 26 (21-30) days, P=0.000], thyroid weight (93.5±33.6, 90.3±48.8, and 74.1±26.0 g, P=0.003), and μCi/g (84.8±11.8, 100.4±24.9, and 121.1±44.0 μCi/g, P=0.000). Interestingly, μCi/g was negatively and positively correlated to the possibility of hormone increase and decrease, respectively. No significant differences were found in the other parameters assessed. At the early stage of I treatment for GD, few patients showed increased thyroid hormone levels. Key factors may include time of ATD discontinuation before I treatment and μCi/g. High μCi/g might decrease thyroid hormone levels in early treatment, making it safe.

  15. Recall and recognition of verbal paired associates in early Alzheimer's disease.

    PubMed

    Lowndes, G J; Saling, M M; Ames, D; Chiu, E; Gonzalez, L M; Savage, G R

    2008-07-01

    The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical samples but this requires further empirical support.

  16. Initial cognitive decline is associated with cortical thinning in early Parkinson disease

    PubMed Central

    Svenningsson, Per; Weintraub, Daniel; Brønnick, Kolbjørn; Lebedev, Alexander; Westman, Eric; Aarsland, Dag

    2014-01-01

    Objectives: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning. Methods: One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. Results: In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample. Conclusions: These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD. PMID:24808018

  17. Neuropsychological correlates of theory of mind in patients with early Parkinson's disease.

    PubMed

    Santangelo, Gabriella; Vitale, Carmine; Trojano, Luigi; Errico, Domenico; Amboni, Marianna; Barbarulo, Anna Maria; Grossi, Dario; Barone, Paolo

    2012-01-01

    The theory of mind is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one's own. The aim of the study was to explore the neuropsychological correlates of theory of mind in patients affected by early Parkinson's disease (PD). Thirty-three PD patients and 33 age-, sex-, and education-matched control subjects underwent the Frontal Assessment Battery, as well as tasks assessing "cognitive" and "affective" theory of mind, and memory abilities; questionnaires evaluating behavioral disorders and quality of life were also administrated. Although the 2 groups did not differ on neuropsychological tasks, PD patients' performance on tasks assessing cognitive and affective theory of mind was significantly worse than controls. Moreover, PD patients had more behavioral disorders and worse quality of life than controls. After covarying for behavioral and quality of life scores, the differences between patients and controls on theory of mind tasks remained significant. "Cognitive" theory of mind was associated with Frontal Assessment Battery score and 2 domains of quality of life scale, whereas "affective" theory of mind scores correlated only with behavioral scales such as the Frontal Behavioral Inventory and Apathy Evaluation Scale. The results demonstrate that both affective and cognitive aspects of theory of mind are simultaneously impaired in early PD and suggest that deficits in the 2 subcomponents of theory of mind may be linked to dysfunction of different frontosubcortical circuitries in early PD. Copyright © 2011 Movement Disorder Society.

  18. Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

    PubMed

    Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

    2018-05-18

    Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

  19. Deep Brain Stimulation for Parkinson’s Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis

    PubMed Central

    Fundament, Tomasz; Eldridge, Paul R.; Green, Alexander L.; Whone, Alan L.; Taylor, Rod S.; Williams, Adrian C.; Schuepbach, W. M. Michael

    2016-01-01

    Background Parkinson’s disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. Methods We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Results Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. Conclusion These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health

  20. Adiposity is associated with early reduction in bone mass in pediatric inflammatory bowel disease.

    PubMed

    Setty-Shah, Nithya; Maranda, Louise; Nwosu, Benjamin Udoka

    2016-01-01

    The effect of adiposity on bone mass in the early phases of inflammatory bowel disease (IBD) in children and adolescents is unclear. The aim of this study was to determine the role of adiposity on bone mass in the first 3 y of diagnosis of IBD. The expected result is that increased adiposity will be associated with increased bone mass in both the controls and IBD subjects. Height-adjusted bone mineral density (BMD) z-scores of 25 subjects, age 13.97 ± 2.70 y, diagnosed with IBD for <4 y were compared to 24 controls, age 13.65 ± 2.60 y. Overweight was defined as BMI of ≥85th but <95th percentile, and obesity as BMI ≥95th percentile. Severity of IBD was determined by the Pediatric Crohn's Disease Activity Index and Lichtiger Colitis Activity Index. Before stratification by BMI criterion, height-adjusted BMD z-scores were not significantly lower in IBD subjects versus controls for both the femoral neck (-0.8 ± 1.1 versus -0.06 ± 1.1, P = 0.070) and lumbar vertebrae (-0.4 ± 1.2 versus 0.2 ± 1.2, P = 0.086). Following stratification, height-adjusted BMD z-scores were significantly lower in the overweight/obese IBD subjects versus overweight/obese controls for femoral neck (-0.9 ± 0.9 versus 0.3 ± 1.3, P = 0.032); and non-significantly lower for the lumbar spine z-score (-0.4 ± 1.6 versus 0.5 ± 1.3, P = 0.197). BMD z-score had no relationship with the duration of disease, steroid therapy, and the severity of disease. Adiposity was associated with reduced bone mass in the early phases of IBD, but with increased bone mass in the controls. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Comparison of composite measures of disease activity in an early seropositive rheumatoid arthritis cohort

    PubMed Central

    Ranganath, Veena K; Yoon, Jeonglim; Khanna, Dinesh; Park, Grace S; Furst, Daniel E; Elashoff, David A; Jawaheer, Damini; Sharp, John T; Gold, Richard H; Keystone, Edward C; Paulus, Harold E

    2007-01-01

    Objective To evaluate concordance and agreement of the original DAS44/ESR‐4 item composite disease activity status measure with nine simpler derivatives when classifying patient responses by European League of Associations for Rheumatology (EULAR) criteria, using an early rheumatoid factor positive (RF+) rheumatoid arthritis (RA) patient cohort. Methods Disease‐modifying anti‐rheumatic drug‐naïve RF+ patients (n = 223; mean duration of symptoms, 6 months) were categorised as ACR none/20/50/70 responders. One‐way analysis of variance and two‐sample t tests were used to investigate the relationship between the ACR response groups and each composite measure. EULAR reached/change cut‐point scores were calculated for each composite measure. EULAR (good/moderate/none) responses for each composite measure and the degree of agreement with the DAS44/ESR‐4 item were calculated for 203 patients. Results Patients were mostly female (78%) with moderate to high disease activity. A centile‐based nomogram compared equivalent composite measure scores. Changes from baseline in the composite measures in patients with ACRnone were significantly less than those of ACR20/50/70 responders, and those for ACR50 were significantly different from those for ACR70. EULAR reached/change cut‐point scores for our cohort were similar to published cut‐points. When compared with the DAS44/ESR‐4 item, EULAR (good/moderate/none) percentage agreements were 92 with the DAS44/ESR‐3 item, 74 with the Clinical Disease Activity Index, and 80 with the DAS28/ESR‐4 item, the DAS28/CRP‐4 item and the Simplified Disease Activity Index. Conclusion The relationships of nine different RA composite measures against the DAS44/ESR‐4 item when applied to a cohort of seropositive patients with early RA are described. Each of these simplified status and response measures could be useful in assessing patients with RA, but the specific measure selected should be pre‐specified and

  2. Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

    PubMed

    Kurz, Ella; Davis, Deborah

    2015-04-17

    Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

  3. Functional and morphological assessment of ocular structures and follow-up of patients with early-stage Parkinson's disease.

    PubMed

    Hasanov, Samir; Demirkilinc Biler, Elif; Acarer, Ahmet; Akkın, Cezmi; Colakoglu, Zafer; Uretmen, Onder

    2018-05-09

    To evaluate and follow-up of functional and morphological changes of the optic nerve and ocular structures prospectively in patients with early-stage Parkinson's disease. Nineteen patients with a diagnosis of early-stage Parkinson's disease and 19 age-matched healthy controls were included in the study. All participants were examined minimum three times at the intervals of at least 6 month following initial examination. Pattern visually evoked potentials (VEP), contrast sensitivity assessments at photopic conditions, color vision tests with Ishihara cards and full-field visual field tests were performed in addition to measurement of retinal nerve fiber layer (RNFL) thickness of four quadrants (top, bottom, nasal, temporal), central and mean macular thickness and macular volumes. Best corrected visual acuity was observed significantly lower in study group within all three examinations. Contrast sensitivity values of the patient group were significantly lower in all spatial frequencies. P100 wave latency of VEP was significantly longer, and amplitude was lower in patient group; however, significant deterioration was not observed during the follow-up. Although average peripapillary RNFL thickness was not significant between groups, RNFL thickness in the upper quadrant was thinner in the patient group. While there was no difference in terms of mean macular thickness and total macular volume values between the groups initially, a significant decrease occurred in the patient group during the follow-up. During the initial and follow-up process, a significant deterioration in visual field was observed in the patient group. Structural and functional disorders shown as electro-physiologically and morphologically exist in different parts of visual pathways in early-stage Parkinson's disease.

  4. [Utility of axial images in an early Alzheimer disease diagnosis support system (VSRAD)].

    PubMed

    Goto, Masami; Aoki, Shigeki; Abe, Osamu; Masumoto, Tomohiko; Watanabe, Yasushi; Satake, Yoshiroh; Nishida, Katsuji; Ino, Kenji; Yano, Keiichi; Iida, Kyohhito; Mima, Kazuo; Ohtomo, Kuni

    2006-09-20

    In recent years, voxel-based morphometry (VBM) has become a popular tool for the early diagnosis of Alzheimer disease. The Voxel-Based Specific Regional Analysis System for Alzheimer's Disease (VSRAD), a VBM system that uses MRI, has been reported to be clinically useful. The able-bodied person database (DB) of VSRAD, which employs sagittal plane imaging, is not suitable for analysis by axial plane imaging. However, axial plane imaging is useful for avoiding motion artifacts from the eyeball. Therefore, we created an able-bodied person DB by axial plane imaging and examined its utility. We also analyzed groups of able-bodied persons and persons with dementia by axial plane imaging and reviewed the validity. After using the DB of axial plane imaging, the Z-score of the intrahippocampal region improved by 8 in 13 instances. In all brains, the Z-score improved by 13 in all instances.

  5. Targeting early PKCθ-dependent T-cell infiltration of dystrophic muscle reduces disease severity in a mouse model of muscular dystrophy.

    PubMed

    Lozanoska-Ochser, Biliana; Benedetti, Anna; Rizzo, Giuseppe; Marrocco, Valeria; Di Maggio, Rosanna; Fiore, Piera; Bouche, Marina

    2018-03-01

    Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre-necrotic stage of muscular dystrophy as the relevant time frame for T-cell-based interventions. We focused on protein kinase C θ (PKCθ, encoded by Prkcq), a critical regulator of effector T-cell activation, as a potential target to inhibit T-cell activity in dystrophic muscle. Lack of PKCθ not only reduced the frequency and number of infiltrating T cells but also led to quantitative and qualitative changes in the innate immune cell infiltrate in mdx/Prkcq -/- muscle. These changes were due to the inhibition of T cells, since PKCθ was necessary for T-cell but not for myeloid cell infiltration of acutely injured muscle. Targeting T cells with a PKCθ inhibitor early in the disease process markedly diminished the size of the inflammatory cell infiltrate and resulted in reduced muscle damage. Moreover, diaphragm necrosis and fibrosis were also reduced following treatment. Overall, our findings identify the early T-cell infiltrate as a therapeutic target and highlight the potential of PKCθ inhibition as a therapeutic approach to muscular dystrophy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. White Matter Integrity Linked To Functional Impairments in Aging and Early Alzheimer’s Disease

    PubMed Central

    Kavcic, Voyko; Ni, Hongyan; Zhu, Tong; Zhong, Jianhui; Duffy, Charles J.

    2008-01-01

    Background Alzheimer’s disease (AD) is associated with changes in cerebral white matter (WM) but the functional significance of such findings is not yet established. We hypothesized that diffusion tensor imaging (DTI) might reveal links between regional WM changes and specific neuropsychologically and psychophysically defined impairments in early AD. Methods Older adult control subjects (OA, n=18) and mildly impaired AD patients (n=14) underwent neuropsychological and visual perceptual testing along with DTI of cerebral WM. DTI yielded factional anisotropy (FA) and mean diffusivity () maps for nine ROIs in three brain regions that were then compared to the performance measures. Results AD patients showed non-significant trends toward lower FAs in the posterior region’s callosal and sub-cortical ROIs. However, posterior callosal FA was significantly correlated with verbal fluency and figural memory impairments, whereas posterior subcortical FA was correlated with delayed verbal memory, figural memory, and optic flow perceptual impairments. Conclusions WM changes in early AD are concentrated in posterior cerebral areas with distributions that correspond to specific functional impairments. DTI can be used to assess regional pathology related to individual’s deficits in early AD. PMID:19012862

  7. Tracking early decline in cognitive function in older individuals at risk for Alzheimer's disease dementia: the Alzheimer's Disease Cooperative Study Cognitive Function Instrument

    PubMed Central

    Amariglio, Rebecca E.; Donohue, Michael C.; Marshall, Gad A.; Rentz, Dorene M.; Salmon, David P.; Ferris, Steven H.; Karantzoulis, Stella; Aisen, Paul S.; Sperling, Reisa A.

    2015-01-01

    Importance Several large-scale Alzheimer's disease (AD) secondary prevention trials have begun to target individuals at the preclinical stage. The success of these trials depends on validated outcome measures that are sensitive to early clinical progression in individuals who are initially asymptomatic. Objective To investigate the utility of the Cognitive Function Instrument (CFI) to track early changes in cognitive function in older individuals without clinical impairment at baseline. Design, Setting, and Participants Longitudinal study over the course of 48 months at participating Alzheimer's Disease Cooperative Study (ADCS) sites. The study included 468 healthy older individuals (Clinical Dementia Rating Scale [CDR] Global = 0, above cut-off on modified Mini-Mental State Exam and Free and Cued Selective Reminding Test) (mean age= 79.4 years ±3.6). All subjects and their study partners completed the Self and Partner CFI annually. Subjects also underwent concurrent annual neuropsychological assessment and apolipoprotein E (APOE) genotyping. Main outcomes and measures Comparison of CFI scores between clinical progressors (Clinical Dementia Rating Scale [CDR] ≥ 0.5) and non-progressors (CDR remained = 0), as well as between APOE ε4 carriers and non-carriers were performed. Correlations of change between the CFI and neuropsychological performance were assessed longitudinally. Results At 48 months, group differences between clinical progressors and non-progressors were significant for CFI Self, CFI Partner, and CFI Self+Partner total scores. At month 48, APOE ε4 carriers showed greater progression than non-carriers on CFI Partner and CFI Self+Partner scores. Both CFI Self and CFI Partner scores were associated with longitudinal cognitive decline, although findings suggest self report may be more accurate early in the process, whereas accuracy of partner report improves when there is progression to cognitive impairment. Conclusions and Relevance Demonstrating

  8. A randomised trial of early palliative care for maternal stress in infants prenatally diagnosed with single-ventricle heart disease.

    PubMed

    Hancock, Hayley S; Pituch, Ken; Uzark, Karen; Bhat, Priya; Fifer, Carly; Silveira, Maria; Yu, Sunkyung; Welch, Suzanne; Donohue, Janet; Lowery, Ray; Aiyagari, Ranjit

    2018-04-01

    Children with single-ventricle disease experience high mortality and complex care. In other life-limiting childhood illnesses, paediatric palliative care may mitigate maternal stress. We hypothesised that early palliative care in the single-ventricle population may have the same benefit for mothers. In this pilot randomised trial of early palliative care, mothers of infants with prenatal single-ventricle diagnoses completed surveys measuring depression, anxiety, coping, and quality of life at a prenatal visit and neonatal discharge. Infants were randomised to receive early palliative care - structured evaluation, psychosocial/spiritual, and communication support before surgery - or standard care. Among 56 eligible mothers, 40 enrolled and completed baseline surveys; 38 neonates were randomised, 18 early palliative care and 20 standard care; and 34 postnatal surveys were completed. Baseline Beck Depression Inventory-II and State-Trait Anxiety Index scores exceeded normal pregnant sample scores (mean 13.76±8.46 versus 7.0±5.0 and 46.34±12.59 versus 29.8±6.35, respectively; p=0.0001); there were no significant differences between study groups. The early palliative care group had a decrease in prenatal to postnatal State-Trait Anxiety Index scores (-7.6 versus 0.3 in standard care, p=0.02), higher postnatal Brief Cope Inventory positive reframing scores (p=0.03), and a positive change in PedsQL Family Impact Module communication and family relationships scores (effect size 0.46 and 0.41, respectively). In conclusion, these data show that mothers of infants with single-ventricle disease experience significant depression and anxiety prenatally. Early palliative care resulted in decreased maternal anxiety, improved maternal positive reframing, and improved communication and family relationships.

  9. Early-onset sleep defects in Drosophila models of Huntington's disease reflect alterations of PKA/CREB signaling

    PubMed Central

    Gonzales, Erin D.; Tanenhaus, Anne K.; Zhang, Jiabin; Chaffee, Ryan P.; Yin, Jerry C.P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention. PMID:26604145

  10. Rheumatic heart disease in pregnancy: How can health services adapt to the needs of Indigenous women? A qualitative study.

    PubMed

    Belton, Suzanne; Kruske, Sue; Jackson Pulver, Lisa; Sherwood, Juanita; Tune, Kylie; Carapetis, Jonathan; Vaughan, Geraldine; Peek, Michael; McLintock, Claire; Sullivan, Elizabeth

    2017-11-06

    To study rheumatic heart disease health literacy and its impact on pregnancy, and to identify how health services could more effectively meet the needs of pregnant women with rheumatic heart disease. Researchers observed and interviewed a small number of Aboriginal women and their families during pregnancy, childbirth and postpartum as they interacted with the health system. An Aboriginal Yarning method of relationship building over time, participant observations and interviews with Aboriginal women were used in the study. The settings were urban, island and remote communities across the Northern Territory. Women were followed interstate if they were transferred during pregnancy. The participants were pregnant women and their families. We relied on participants' abilities to tell their own experiences so that researchers could interpret their understanding and perspective of rheumatic heart disease. Aboriginal women and their families rarely had rheumatic heart disease explained appropriately by health staff and therefore lacked understanding of the severity of their illness and its implications for childbearing. Health directives in written and spoken English with assumed biomedical knowledge were confusing and of limited use when delivered without interpreters or culturally appropriate health supports. Despite previous studies documenting poor communication and culturally inadequate care, health systems did not meet the needs of pregnant Aboriginal women with rheumatic heart disease. Language-appropriate health education that promotes a shared understanding should be relevant to the gender, life-stage and social context of women with rheumatic heart disease. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  11. Estrogenic exposure affects metamorphosis and alters sex ratios in the northern leopard frog (Rana pipiens): identifying critically vulnerable periods of development.

    PubMed

    Hogan, Natacha S; Duarte, Paula; Wade, Michael G; Lean, David R S; Trudeau, Vance L

    2008-05-01

    During the transformation from larval tadpole to juvenile frog, there are critical periods of metamorphic development and sex differentiation that may be particularly sensitive to endocrine disruption. The aim of the present study was to identify sensitive developmental periods for estrogenic endocrine disruption in the northern leopard frog (Rana pipiens) using short, targeted exposures to the synthetic estrogen, ethinylestradiol (EE2). Post-hatch tadpoles (Gosner stage 27) were exposed over five distinct periods of metamorphosis: early (stage 27-30), mid (stage 30-36), early and mid (stage 27-36), late (stage 36-42), and the entire metamorphic period (chronic; stage 27-42). For each period, animals were sampled immediately following the EE2 exposure and at metamorphic climax (stage 42). The effects of EE2 on metamorphic development and sex differentiation were assessed through measures of length, weight, developmental stage, days to metamorphosis, sex ratios and incidence of gonadal intersex. Our results show that tadpoles exposed to EE2 during mid-metamorphosis were developmentally delayed immediately following exposure and took 2 weeks longer to reach metamorphic climax. In the unexposed groups, there was low proportion (0.15) of intersex tadpoles at stage 30 and gonads appeared to be morphologically distinct (male and female) in all individuals by stage 36. Tadpoles exposed early in development displayed a strong female-biased sex ratio compared to the controls. Moreover, these effects were also seen at metamorphic climax, approximately 2-3 months after the exposure period, demonstrating that transient early life-stage exposure to estrogen can induce effects on the reproductive organs that persist into the beginning of adult life-stages.

  12. Targeting Aβ and tau in Alzheimer's disease, an early interim report

    PubMed Central

    Golde, Todd E.; Petrucelli, Leonard; Lewis, Jada

    2009-01-01

    The amyloid β (Aβ) and tau proteins, which misfold, aggregate, and accumulate in the Alzheimer's disease (AD) brain, are implicated as central factors in a complex neurodegenerative cascade. Studies of mutations that cause early onset AD and promote Aβ accumulation in the brain strongly support the notion that inhibiting Aβ aggregation will prevent AD. Similarly, genetic studies of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17 MAPT) showing that mutations in the MAPT gene encoding tau lead to abnormal tau accumulation and neurodegeneration. Such genetic studies clearly show that tau dysfunction and aggregation can be central to neurodegeneration, however, most likely in a secondary fashion in relation to AD. Additional pathologic, biochemical and modeling studies further support the concept that Aβ and tau are prime targets for disease modifying therapies in AD. Treatment strategies aimed at preventing the aggregation and accumulation of Aβ, tau, or both proteins should therefore be theoretically possible, assuming that treatment can be initiated before either irreversible damage is present or downstream, self-sustaining, pathological cascades have been initiated. Herein, we will review recent advances and also potential setbacks with respect to the myriad of therapeutic strategies that are designed to slow down, prevent, or clear the accumulation of either “pathological” Aβ or tau. We will also discuss the need for thoughtful prioritization with respect to clinical development of the pre-clinically validated modifiers of Aβ and tau pathology. The current number of candidate therapies targeting Aβ is becoming so large that a triage process is clearly needed to insure that resources are invested in a way such that the best candidates for disease modifying therapy are rapidly moved toward clinical trials. Finally, we will discuss the challenges for an appropriate “triage” after potential disease modifying therapies

  13. MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

    PubMed Central

    Arshad, Ahmad R.; Sulaiman, Siti A.; Saperi, Amalia A.; Jamal, Rahman; Mohamed Ibrahim, Norlinah; Abdul Murad, Nor Azian

    2017-01-01

    Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis. PMID:29163029

  14. Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.

    PubMed

    Stout, Julie C; Jones, Rebecca; Labuschagne, Izelle; O'Regan, Alison M; Say, Miranda J; Dumas, Eve M; Queller, Sarah; Justo, Damian; Santos, Rachelle Dar; Coleman, Allison; Hart, Ellen P; Dürr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Langbehn, Doug R; Tabrizi, Sarah J; Frost, Chris

    2012-07-01

    Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials. There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks. 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls. The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD.

  15. Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson’s Disease: A Critical Review

    PubMed Central

    Nair, Arun T; Ramachandran, Vadivelan; Joghee, Nanjan M; Antony, Shanish; Ramalingam, Gopalakrishnan

    2018-01-01

    Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients. PMID:29291606

  16. A Bayesian Model for the Prediction and Early Diagnosis of Alzheimer's Disease.

    PubMed

    Alexiou, Athanasios; Mantzavinos, Vasileios D; Greig, Nigel H; Kamal, Mohammad A

    2017-01-01

    Alzheimer's disease treatment is still an open problem. The diversity of symptoms, the alterations in common pathophysiology, the existence of asymptomatic cases, the different types of sporadic and familial Alzheimer's and their relevance with other types of dementia and comorbidities, have already created a myth-fear against the leading disease of the twenty first century. Many failed latest clinical trials and novel medications have revealed the early diagnosis as the most critical treatment solution, even though scientists tested the amyloid hypothesis and few related drugs. Unfortunately, latest studies have indicated that the disease begins at the very young ages thus making it difficult to determine the right time of proper treatment. By taking into consideration all these multivariate aspects and unreliable factors against an appropriate treatment, we focused our research on a non-classic statistical evaluation of the most known and accepted Alzheimer's biomarkers. Therefore, in this paper, the code and few experimental results of a computational Bayesian tool have being reported, dedicated to the correlation and assessment of several Alzheimer's biomarkers to export a probabilistic medical prognostic process. This new statistical software is executable in the Bayesian software Winbugs, based on the latest Alzheimer's classification and the formulation of the known relative probabilities of the various biomarkers, correlated with Alzheimer's progression, through a set of discrete distributions. A user-friendly web page has been implemented for the supporting of medical doctors and researchers, to upload Alzheimer's tests and receive statistics on the occurrence of Alzheimer's disease development or presence, due to abnormal testing in one or more biomarkers.

  17. Diagnostic tools of early brain disturbances in an asymptomatic neonate with maple syrup urine disease.

    PubMed

    Terek, Demet; Koroglu, Ozge; Yalaz, Mehmet; Gokben, Sarenur; Calli, Cem; Coker, Mahmut; Kultursay, Nilgun

    2013-08-01

    Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder resulting from the defective activity of branched-chain 2-ketoacid dehydrogenase complex. Routine screening of newborn with tandem mass spectroscopy on the third day of life may detect elevated branched-chain amino acids in blood before the appearance of encephalopathic symptoms in MSUD cases. If undiagnosed by such a routine screening test, patients often present with encephalopathy and seizures. Clinical neurologic examination is supplemented by electroencephalography and imaging. Here, we report abnormal amplitude-integrated electroencephalography, electroencephalography, magnetic resonance imaging, and magnetic resonance imaging spectroscopy findings in a neurologically asymptomatic male newborn who was diagnosed with MSUD at the third week of life. These neurologic disturbances disappeared at the fourth month of life with appropriate special diet. Therefore, even in already asymptomatic cases, early neurologic deterioration of brain metabolism and structure can be detected with these early laboratory findings, indicating the importance of early diagnosis and management. Patients may also benefit from these investigations during the follow-up period. Georg Thieme Verlag KG Stuttgart · New York.

  18. Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life.

    PubMed

    Axelrud, Luiza K; Santoro, Marcos L; Pine, Daniel S; Talarico, Fernanda; Gadelha, Ary; Manfro, Gisele G; Pan, Pedro M; Jackowski, Andrea; Picon, Felipe; Brietzke, Elisa; Grassi-Oliveira, Rodrigo; Bressan, Rodrigo A; Miguel, Eurípedes C; Rohde, Luis A; Hakonarson, Hakon; Pausova, Zdenka; Belangero, Sintia; Paus, Tomas; Salum, Giovanni A

    2018-06-01

    Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume. Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project. Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar for the Brazilian replication sample (immediate and delayed recall, β=-0.259 and β=-0.232, both significant). Quantile regressions showed lower hippocampal volumes bilaterally for individuals with high polygenic risk scores. Associations fell short of significance for the Canadian sample. Genetic risk for Alzheimer's disease may affect early-life cognition and hippocampal volumes, as shown in two independent samples. These data support previous evidence that some forms of late-life dementia may represent developmental conditions with roots in childhood. This result may vary depending on a sample's genetic risk and may be specific to some types of memory tasks.

  19. [Study on early intervention of compound nutrition for cognitive dysfunction in Alzheimer's disease].

    PubMed

    Wang, Chao; Xie, Wei; Zhu, Jinfeng; Dang, Rui; Wang, Decai

    2014-01-01

    To observe the early prevention effect of the compound nutrients recipe for cognitive dysfunction of Alzheimer' s disease model-APP-PSN transgenic mouse. 36 APP-PSN transgenic mice aged two months randomly were divided into the intervention group supplied with compound recipe in the diet and the control group fed based feed, the former had high dose and low dose, 12 APP-PSN transgenic negative mice aged two months as the negative control were fed based feed. After 3 months' intervention, four groups' cognitive functions were evaluated using the Morris water maze, active avoidance experiment and jumping stair experiment. There was not statistically different between all the four groups for the weight and food intake. Compared with the control group, Morris water maze's incubation period of the intervention group was lower obviously, and jumping stair experiment's incubation period of the intervention group was higher obviously. In the active avoidance experiment, the high and low dose intervention group' s conditioned response accounted about 46.67% and 45.00% respectively, and the control group's conditioned response accounted about 20.83%. The differences of the three behavioral experiments between control group and intervention group had the statistical significance (P < 0.05), so the same as between control group and negative control group (P < 0.05). And there was no difference between intervention group and negative control group for the three behavioral experiments. The early supplementation with compound nutrition could postpone the occurrence and development of Alzheimer' s disease mice model's cognitive dysfunction.

  20. Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

    PubMed Central

    2015-01-01

    Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo