Science.gov

Sample records for impaired drug-binding capacity

  1. Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro

    PubMed Central

    Olsen, Harald; Andersen, Anders; Nordbø, Arve; Kongsgaard, Ulf E; Børmer, Ole P

    2004-01-01

    Background Albumin is the most abundant protein in blood plasma, and due to its ligand binding properties, serves as a circulating depot for endogenous and exogenous (e.g. drugs) compounds. Hence, the unbound drug is the pharmacologically active drug. Commercial human albumin preparations are frequently used during surgery and in critically ill patients. Recent studies have indicated that the use of pharmaceutical-grade albumin is controversial in critically ill patients. In this in vitro study we investigated the drug binding properties of pharmaceutical-grade albumins (Baxter/Immuno, Octapharma, and Pharmacia & Upjohn), native human serum, and commercially available human serum albumin from Sigma Chemical Company. Methods The binding properties of the various albumin solutions were tested in vitro by means of ultrafiltration. Naproxen, warfarin, and digitoxin were used as ligands. HPLC was used to quantitate the total and free drug concentrations. The data were fitted to a model of two classes of binding sites for naproxen and warfarin and one class for digitoxin, using Microsoft Excel and Graphpad Prism. Results The drugs were highly bound to albumin (95–99.5%). The highest affinity (lowest K1) was found with naproxen. Pharmaceutical-grade albumin solutions displayed significantly lower drug-binding capacity compared to native human serum and Sigma albumin. Thus, the free fraction was considerably higher, approximately 40 times for naproxen and 5 and 2 times for warfarin and digitoxin, respectively. The stabilisers caprylic acid and N-acetyl-DL-tryptophan used in the manufacturing procedure seem to be of importance. Adding the stabilisers to human serum and Sigma albumin reduced the binding affinity whereas charcoal treatment of the pharmaceutical-grade albumin from Octapharma almost restored the specific binding capacity. Conclusion This in vitro study demonstrates that the specific binding for warfarin and digitoxin is significantly reduced and for naproxen

  2. Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity[S

    PubMed Central

    Vaisar, Tomáš; Tang, Chongren; Babenko, Ilona; Hutchins, Patrick; Wimberger, Jake; Suffredini, Anthony F.; Heinecke, Jay W.

    2015-01-01

    Recent studies demonstrate that HDL’s ability to promote cholesterol efflux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL’s major protein. However, the mechanisms that impair cholesterol efflux capacity during vascular disease are unclear. Inflammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL’s cholesterol efflux capacity. We therefore tested the hypothesis that HDL’s impaired efflux capacity is mediated by specific changes of its protein cargo. Humans with acute inflammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C efflux capacity was significantly impaired. Proteomic analyses demonstrated that HDL’s cholesterol efflux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute inflammation caused a marked impairment of HDL-C efflux capacity that correlated with a large increase in HDL SAA. In striking contrast, the efflux capacity of mouse inflammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the inflammatory impairment of HDL-C efflux capacity is due in part to SAA-mediated remodeling of HDL’s protein cargo. PMID:25995210

  3. Clinical relevance of drug binding to plasma proteins

    NASA Astrophysics Data System (ADS)

    Ascenzi, Paolo; Fanali, Gabriella; Fasano, Mauro; Pallottini, Valentina; Trezza, Viviana

    2014-12-01

    Binding to plasma proteins highly influences drug efficacy, distribution, and disposition. Serum albumin, the most abundant protein in plasma, is a monomeric multi-domain macromolecule that displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds, such as fatty acids and most acidic drugs. α-1-Acid glycoprotein, the second main plasma protein, is a glycoprotein physiologically involved in the acute phase reaction and is the main carrier for basic and neutral drugs. High- and low-density lipoproteins play a limited role in drug binding and are natural drug delivery system only for few lipophilic drugs or lipid-based formulations. Several factors influence drug binding to plasma proteins, such as pathological conditions, concurrent administration of drugs, sex, and age. Any of these factors, in turn, influences drug efficacy and toxicity. Here, biochemical, biomedical, and biotechnological aspects of drug binding to plasma proteins are reviewed.

  4. Variable Judgments of Decisional Capacity in Cognitively Impaired Research Subjects

    PubMed Central

    Stocking, Carol B.; Hougham, Gavin W.; Danner, Deborah D.; Patterson, Marion B.; Whitehouse, Peter J.; Sachs, Greg A.

    2008-01-01

    OBJECTIVES To compare assessments of the decisional capacity of cognitively impaired patients by research assistants (RAs) and by family caregiver/proxies; and to determine whether either or both groups judge capacity differently depending on the specific (hypothetical) research enrollment decision being made. DESIGN Cross sectional SETTING Three clinics, one each in Ohio, Kentucky and Illinois PARTICIPANTS 149 patients with established dementia diagnoses and their caregiver/proxies MEASUREMENTS As part of a longer interview, patients were asked about future enrollment in five hypothetical research projects with varying risks and benefits. After patients reported each decision and reasons for that decision, RAs (using Applebaum & Grisso’s four standards) indicated whether the patient was competent to make that decision on their own. In separate interviews, caregiver/proxies were asked for a similar appraisal based on life experience with the patient. RA and proxy judgments were compared. RESULTS Capacity judgments by RAs and by caregivers differed by specific project for most patients. Agreement between RA and proxy judgments varied by project but agreement was only “fair’ when tested by kappa (range in data .21 - .39). There were 50 patients who were appraised as competent for all decisions by proxies and 47 who were so assessed by RAs. Of these only 24 were the same patients. CONCLUSION If capacity were assessed anew for each enrollment decision, more potential participants could maintain authority in making those decisions. PMID:19054202

  5. Schizophrenia: An Impairment in the Capacity to Perceive Affordances

    PubMed Central

    Kim, Nam-Gyoon; Kim, Hakboon

    2017-01-01

    Phenomenological psychopathologists conceptualize schizophrenia as a self-disorder involving profound distortions of selfhood. For James Gibson, “to perceive the world is to coperceive oneself.” If the sense of self is disturbed in individuals with schizophrenia, this could also lead to disturbances in these individuals’ ability to perceive affordances, environmental properties taken with reference to the perceiver’s action capabilities (e.g., a rigid surface affording ‘walk-on-able,’ chairs ‘sit-on-able,’ and so on). To test this hypothesis, three experiments investigated schizophrenia patients’ affordance perception. Participants were presented with a photo of a common object on the computer and then asked to judge its secondary affordance (a non-designed function) in a two-choice reaction time task in Experiment 1 and in a yes/no task in Experiment 2. Schizophrenia participants performed less accurately and more slowly than controls. To rule out visual impairment as a contributing factor, in Experiment 3, participants identified physical properties (color, shape, material composition) of the objects. Schizophrenia participants were as accurate as controls and responded faster than in the previous experiments. Results suggest that the capacity to perceive affordances is likely impaired in people with schizophrenia, although the capacity to detect the object’s physical properties is kept intact. Inability to perceive affordances, those functionally significant properties of the surrounding environment, may help explain why schizophrenia patients may appear as somewhat detached from the world. PMID:28701973

  6. Loss of Adipocyte VEGF Impairs Endurance Exercise Capacity in Mice.

    PubMed

    Zachwieja, Nicole J; O'Connell, Grant C; Stricker, Janelle C; Allen, Jessica; Vona-Davis, Linda; Bryner, Randall; Mandler, William; Olfert, I Mark

    2015-11-01

    Reducing vascular endothelial growth factor (VEGF) in adipose tissue alters adipose vascularity and metabolic homeostasis. We hypothesized that this would also affect metabolic responses during exercise-induced stress and that adipocyte-specific VEGF-deficient (adipoVEGF-/-) mice would have impaired endurance capacity. Endurance exercise capacity in adipoVEGF-/- (n = 10) and littermate control (n = 11) mice was evaluated every 4 wk between 6 and 24 wk of age using a submaximal endurance run to exhaustion at 20 m·min(-1) at 10° incline. Maximal running speed, using incremental increases in speed at 30-s intervals, was tested at 25 and 37 wk of age. White and brown adipose tissue capillarity were reduced by 40% in adipoVEGF-/-, and no difference in skeletal muscle capillarity was observed. Endurance run time to exhaustion was 30% lower in adipoVEGF-/- compared with that in controls at all time points (P < 0.001), but no difference in maximal running speed was observed between the groups. After exercise (1 h at 50% maximum running speed), adipoVEGF-/- mice displayed lower circulating insulin (P < 0.001), lower glycerol (P < 0.05), and tendency for lower blood glucose (P = 0.06) compared with controls. There was no evidence of altered oxidative damage or changes in carnitine palmitoyltransferase-1β expression in skeletal muscle of adipoVEGF-/- mice. These data suggest that VEGF-mediated deficits in adipose tissue blunt the availability of lipid substrates during endurance exercise, which likely reduced endurance performance. Surprisingly, we also found an unchanged basal blood glucose despite lower circulating insulin in adipoVEGF-/- mice, suggesting that loss of adipocyte VEGF can blunt insulin release and/or increase basal insulin sensitivity.

  7. Loss of Adipocyte VEGF Impairs Endurance Exercise Capacity in Mice

    PubMed Central

    Zachwieja, Nicole J.; O’Connell, Grant C.; Stricker, Janelle C.; Allen, Jessica; Vona-Davis, Linda; Bryner, Randall; Mandler, William; Olfert, I. Mark

    2015-01-01

    Purpose Reducing vascular endothelial growth factor (VEGF) in adipose tissue alters adipose vascularity and metabolic homeostasis. We hypothesized that this would also affect metabolic responses during exercise-induced stress, and that adipocyte-specific VEGF deficient (adipoVEGF−/−) mice would have impaired endurance capacity. Methods Endurance exercise capacity in adipoVEGF−/− (n=10) and littermate control (n=11) mice was evaluated every 4 weeks between 6 & 24 weeks of age using a submaximal endurance run to exhaustion at 20 m/min, 10-degree incline. Maximal running speed, using incremental increases in speed at 30-second intervals, was tested at 25 weeks of age. Results White and brown adipose tissue capillarity were reduced by 40% in adipoVEGF−/−, and no difference in skeletal muscle capillarity was observed. Endurance run time to exhaustion was 30% lower in adipoVEGF−/− compared to controls at all time points (p<0.001), but no difference in maximal running speed was observed between the groups. Following exercise (1 hour at 50% maximum running speed), adipoVEGF−/− mice displayed lower circulating insulin, (p<0.001), lower glycerol (p<0.05), and a tendency for lower blood glucose (p=0.06) compared to controls. There was no evidence of altered oxidative damage or changes in carnitine palmitoyltransferase-1β expression in skeletal muscle of adipoVEGF−/− mice. Conclusions These data suggest that VEGF-mediated deficits in adipose tissue blunts the availability of lipid substrates during endurance exercise, both of which likely reduce endurance performance. Surprisingly, we also find an unchanged basal blood glucose, despite lower circulating insulin in adipoVEGF−/− mice, suggesting loss of adipocyte VEGF can blunt insulin release and/or increase basal insulin sensitivity. PMID:25785931

  8. Higher Self-Control Capacity Predicts Lower Anxiety-Impaired Cognition during Math Examinations

    PubMed Central

    Bertrams, Alex; Baumeister, Roy F.; Englert, Chris

    2016-01-01

    We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition 5 months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests. PMID:27065013

  9. A clinical decision algorithm for hospital inpatients with impaired decision-making capacity.

    PubMed

    Chase, Jack

    2014-08-01

    Impaired decision-making capacity is a frequent complication of inpatient hospitalization, with potential negative impacts on patients and the healthcare system. Studies of clinician behavior show difficulty in diagnosis and management of capacity impairment. Appropriate management of incapacitated patients may benefit safety, medical outcomes, and healthcare expenditure. To create a clinical decision algorithm for identification and management of hospital inpatients with impaired capacity. The Department of Risk Management at San Francisco General Hospital (SFGH) convened a multidisciplinary workgroup to improve management of incapacitated patients. The workgroup studied institutional data and case experience, solicited mental health expertise, and performed a brief review of published tools for management of incapacitated patients. The workgroup produced a clinical decision algorithm for hospital inpatients with impaired decision-making capacity. The algorithm is explained via 3 common scenarios, and notable details include identification and management in a single visual diagram, emphasis on safety planning for a high-risk subset of incapacitated patients, and explanation for multiple disciplines of consultation. The algorithm was disseminated to providers, workshops were conducted, and associated quality improvements were implemented. Initial feedback was positive, relating to clinical competency, decreased practice anxiety, and improved teamwork. Impaired decision-making capacity is frequent among hospitalized patients, including at SFGH. An algorithm, based on institutional review and prior published work, is presented as an example to address the common challenge of acutely ill patients with impaired decision-making capacity. © 2014 Society of Hospital Medicine.

  10. Progressively impaired proteasomal capacity during terminal plasma cell differentiation

    PubMed Central

    Cenci, Simone; Mezghrani, Alexandre; Cascio, Paolo; Bianchi, Giada; Cerruti, Fulvia; Fra, Anna; Lelouard, Hugues; Masciarelli, Silvia; Mattioli, Laura; Oliva, Laura; Orsi, Andrea; Pasqualetto, Elena; Pierre, Philippe; Ruffato, Elena; Tagliavacca, Luigina; Sitia, Roberto

    2006-01-01

    After few days of intense immunoglobulin (Ig) secretion, most plasma cells undergo apoptosis, thus ending the humoral immune response. We asked whether intrinsic factors link plasma cell lifespan to Ig secretion. Here we show that in the late phases of plasmacytic differentiation, when antibody production becomes maximal, proteasomal activity decreases. The excessive load for the reduced proteolytic capacity correlates with accumulation of polyubiquitinated proteins, stabilization of endogenous proteasomal substrates (including Xbp1s, IκBα, and Bax), onset of apoptosis, and sensitization to proteasome inhibitors (PI). These events can be reproduced by expressing Ig-μ chain in nonlymphoid cells. Our results suggest that a developmental program links plasma cell death to protein production, and help explaining the peculiar sensitivity of normal and malignant plasma cells to PI. PMID:16498407

  11. Impaired Semantic Knowledge Underlies the Reduced Verbal Short-Term Storage Capacity in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Peters, Frederic; Majerus, Steve; De Baerdemaeker, Julie; Salmon, Eric; Collette, Fabienne

    2009-01-01

    A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor…

  12. Impaired Semantic Knowledge Underlies the Reduced Verbal Short-Term Storage Capacity in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Peters, Frederic; Majerus, Steve; De Baerdemaeker, Julie; Salmon, Eric; Collette, Fabienne

    2009-01-01

    A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor…

  13. Impaired working memory capacity is not caused by failures of selective attention in schizophrenia.

    PubMed

    Erickson, Molly A; Hahn, Britta; Leonard, Carly J; Robinson, Benjamin; Gray, Brad; Luck, Steven J; Gold, James

    2015-03-01

    The cognitive impairments associated with schizophrenia have long been known to involve deficits in working memory (WM) capacity. To date, however, the causes of WM capacity deficits remain unknown. The present study examined selective attention impairments as a putative contributor to observed capacity deficits in this population. To test this hypothesis, we used an experimental paradigm that assesses the role of selective attention in WM encoding and has been shown to involve the prefrontal cortex and the basal ganglia. In experiment 1, participants were required to remember the locations of 3 or 5 target items (red circles). In another condition, 3-target items were accompanied by 2 distractor items (yellow circles), which participants were instructed to ignore. People with schizophrenia (PSZ) exhibited significant impairment in memory for the locations of target items, consistent with reduced WM capacity, but PSZ and healthy control subjects did not differ in their ability to filter the distractors. This pattern was replicated in experiment 2 for distractors that were more salient. Taken together, these results demonstrate that reduced WM capacity in PSZ is not attributable to a failure of filtering irrelevant distractors.

  14. Association Between Exercise Capacity and Late Onset of Dementia, Alzheimer Disease, and Cognitive Impairment.

    PubMed

    Müller, Jan; Chan, Khin; Myers, Jonathan N

    2017-02-01

    To address the association between exercise capacity and the onset of dementia, Alzheimer disease, and cognitive impairment. For 6104 consecutive veteran patients (mean ± SD age: 59.2±11.4 years) referred for treadmill exercise testing, the combined end point of dementia, Alzheimer disease, and cognitive impairment was abstracted from the Veterans Affairs computerized patient record system. After mean ± SD follow-up of 10.3±5.5 years, 353 patients (5.8%) developed the composite end point at a mean ± SD age of 76.7±10.3 years. After correction for confounders in multivariate Cox proportional hazards regression, higher age at exercise testing (hazard ratio [HR]=1.08; 95% CI, 1.07-1.09; P<.001), current smoking (HR=1.44; 95% CI, 1.08-1.93; P=.01), and exercise capacity (HR=0.92; 95% CI, 0.89-0.96; P<.001) emerged as predictors of cognitive impairment. Each 1-metabolic equivalent increase in exercise capacity conferred a nearly 8% reduction in the incidence of cognitive impairment. Meeting the recommendations for daily activity was not associated with a delay in onset of cognitive impairment (HR=1.07; 95% CI, 0.86-1.32; P=.55). Exercise capacity is strongly associated with cognitive function; the inverse association between fitness and cognitive impairment provides an additional impetus for health care providers to promote physical activity. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  15. Impaired Contingent Attentional Capture Predicts Reduced Working Memory Capacity in Schizophrenia

    PubMed Central

    Mayer, Jutta S.; Fukuda, Keisuke; Vogel, Edward K.; Park, Sohee

    2012-01-01

    Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding. PMID:23152783

  16. Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction.

    PubMed

    Giannotti, Giovanna; Doerries, Carola; Mocharla, Pavani S; Mueller, Maja F; Bahlmann, Ferdinand H; Horvàth, Tibor; Jiang, Hong; Sorrentino, Sajoscha A; Steenken, Nora; Manes, Costantina; Marzilli, Mario; Rudolph, K Lenhard; Lüscher, Thomas F; Drexler, Helmut; Landmesser, Ulf

    2010-06-01

    Prehypertension is a highly frequent condition associated with an increased cardiovascular risk. Endothelial dysfunction is thought to promote the development of hypertension and vascular disease; however, underlying mechanisms remain to be further determined. The present study characterizes for the first time the in vivo endothelial repair capacity of early endothelial progenitor cells (EPCs) in patients with prehypertension/hypertension and examines its relation with endothelial function. Early EPCs were isolated from healthy subjects and newly diagnosed prehypertensive and hypertensive patients (n=52). In vivo endothelial repair capacity of EPCs was examined by transplantation into a nude mouse carotid injury model. EPC senescence was determined (RT-PCR of telomere length). NO and superoxide production of EPCs were measured using electron spin resonance spectroscopy analysis. CD34(+)/KDR(+) mononuclear cells and circulating endothelial microparticles were examined by fluorescence-activated cell sorter analysis. Endothelium-dependent and -independent vasodilations were determined by high-resolution ultrasound. In vivo endothelial repair capacity of EPCs was substantially impaired in prehypertensive/hypertensive patients as compared with healthy subjects (re-endothelialized area: 15+/-3%/13+/-2% versus 28+/-3%; P<0.05 versus healthy subjects). Senescence of EPCs in prehypertension/hypertension was substantially increased, and NO production was markedly reduced. Moreover, reduced endothelial repair capacity of early EPCs was significantly related to an accelerated senescence of early EPCs and impaired endothelial function. The present study demonstrates for the first time that in vivo endothelial repair capacity of early EPCs is reduced in patients with prehypertension and hypertension, is related to EPC senescence and impaired endothelial function, and likely represents an early event in the development of hypertension.

  17. Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration

    PubMed Central

    Monette, Jeffrey S.; Hutchins, Patrick M.; Ronsein, Graziella E.; Wimberger, Jake; Irwin, Angela D.; Tang, Chongren; Sara, Jaskanwal D.; Shao, Baohai; Vaisar, Tomas; Lerman, Amir; Heinecke, Jay W.

    2016-01-01

    Rationale Coronary endothelial dysfunction (ED)–an early marker of atherosclerosis–increases the risk of cardiovascular events. Objective We tested the hypothesis that cholesterol efflux capacity and HDL particle concentration predict coronary ED better than HDL-cholesterol (HDL-C). Methods and Results We studied 80 subjects with non-obstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in response to intra-coronary infusions of acetylcholine during diagnostic coronary angiography. Cholesterol efflux capacity and HDL particle concentration (HDL-PIMA) were assessed with validated assays. Cholesterol efflux capacity and HDL-PIMA were both strong, inverse predictors of ED (P<0.001 and 0.005, respectively). In contrast, HDL-C and other traditional lipid risk factors did not differ significantly between control and ED subjects. Large HDL particles were markedly decreased in ED subjects (33%; P=0.005). After correction for HDL-C, both efflux capacity and HDL-PIMA remained significant predictors of ED status. HDL-PIMA explained cholesterol efflux capacity more effectively than HDL-C (r=0.54 and 0.36, respectively). The efflux capacities of isolated HDL and serum HDL correlated strongly (r=0.49). Conclusions Cholesterol efflux capacity and HDL-PIMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-PIMA and HDL itself account for a much larger fraction of the variation in cholesterol efflux capacity than does HDL-C. A selective decrease in large HDL particles may contribute to impaired cholesterol efflux capacity in ED subjects. These observations support a role for HDL size, concentration and function as markers—and perhaps mediators—of coronary atherosclerosis in humans. PMID:27114438

  18. Augmentation of normal and glutamate-impaired neuronal respiratory capacity by exogenous alternative biofuels.

    PubMed

    Laird, Melissa D; Clerc, Pascaline; Polster, Brian M; Fiskum, Gary

    2013-12-01

    Mitochondrial respiratory capacity is critical for responding to changes in neuronal energy demand. One approach toward neuroprotection is the administration of alternative energy substrates ("biofuels") to overcome brain injury-induced inhibition of glucose-based aerobic energy metabolism. This study tested the hypothesis that exogenous pyruvate, lactate, β-hydroxybutyrate, and acetyl-L-carnitine each increase neuronal respiratory capacity in vitro either in the absence of or following transient excitotoxic glutamate receptor stimulation. Compared to the presence of 5 mM glucose alone, the addition of pyruvate, lactate, or β-hydroxybutyrate (1.0-10.0 mM) to either day in vitro (DIV) 14 or 7 rat cortical neurons resulted in significant, dose-dependent stimulation of respiratory capacity, measured by cell respirometry as the maximal O2 consumption rate in the presence of the respiratory uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone. A 30-min exposure to 100 μM glutamate impaired respiratory capacity for DIV 14, but not DIV 7, neurons. Glutamate reduced the respiratory capacity for DIV 14 neurons with glucose alone by 25 % and also reduced respiratory capacity with glucose plus pyruvate, lactate, or β-hydroxybutyrate. However, respiratory capacity in glutamate-exposed neurons following pyruvate or β-hydroxybutyrate addition was still, at least, as high as that obtained with glucose alone in the absence of glutamate exposure. These results support the interpretation that previously observed neuroprotection by exogenous pyruvate, lactate, or β-hydroxybutyrate is at least partially mediated by their preservation of neuronal respiratory capacity.

  19. Exercise training reverses impaired skeletal muscle metabolism induced by artificial selection for low aerobic capacity

    PubMed Central

    Lessard, Sarah J.; Rivas, Donato A.; Stephenson, Erin J.; Yaspelkis, Ben B.; Koch, Lauren G.; Britton, Steven L.

    2011-01-01

    We have used a novel model of genetically imparted endurance exercise capacity and metabolic health to study the genetic and environmental contributions to skeletal muscle glucose and lipid metabolism. We hypothesized that metabolic abnormalities associated with low intrinsic running capacity would be ameliorated by exercise training. Selective breeding for 22 generations resulted in rat models with a fivefold difference in intrinsic aerobic capacity. Low (LCR)- and high (HCR)-capacity runners remained sedentary (SED) or underwent 6 wk of exercise training (EXT). Insulin-stimulated glucose transport, insulin signal transduction, and rates of palmitate oxidation were lower in LCR SED vs. HCR SED (P < 0.05). Decreases in glucose and lipid metabolism were associated with decreased β2-adrenergic receptor (β2-AR), and reduced expression of Nur77 target proteins that are critical regulators of muscle glucose and lipid metabolism [uncoupling protein-3 (UCP3), fatty acid transporter (FAT)/CD36; P < 0.01 and P < 0.05, respectively]. EXT reversed the impairments to glucose and lipid metabolism observed in the skeletal muscle of LCR, while increasing the expression of β2-AR, Nur77, GLUT4, UCP3, and FAT/CD36 (P < 0.05) in this tissue. However, no metabolic improvements were observed following exercise training in HCR. Our results demonstrate that metabolic impairments resulting from genetic factors (low intrinsic aerobic capacity) can be overcome by an environmental intervention (exercise training). Furthermore, we identify Nur77 as a potential mechanism for improved skeletal muscle metabolism in response to EXT. PMID:21048074

  20. Impaired semantic knowledge underlies the reduced verbal short-term storage capacity in Alzheimer's disease.

    PubMed

    Peters, Frédéric; Majerus, Steve; De Baerdemaeker, Julie; Salmon, Eric; Collette, Fabienne

    2009-12-01

    A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor STM performance. The aim of this study was to examine the influence of semantic knowledge on verbal short-term memory storage capacity in normal aging and in AD by exploring the impact of word imageability on STM performance. Sixteen patients suffering from mild AD, 16 healthy elderly subjects and 16 young subjects performed an immediate serial recall task using word lists containing high or low imageability words. All participant groups recalled more high imageability words than low imageability words, but the effect of word imageability on verbal STM was greater in AD patients than in both the young and the elderly control groups. More precisely, AD patients showed a marked decrease in STM performance when presented with lists of low imageability words, whereas recall of high imageability words was relatively well preserved. Furthermore, AD patients displayed an abnormal proportion of phonological errors in the low imageability condition. Overall, these results indicate that the support of semantic knowledge on STM performance was impaired for lists of low imageability words in AD patients. More generally, these findings suggest that the deterioration of semantic knowledge is partly responsible for the poor verbal short-term storage capacity observed in AD.

  1. Substrate and drug binding sites in LeuT.

    PubMed

    Nyola, Ajeeta; Karpowich, Nathan K; Zhen, Juan; Marden, Jennifer; Reith, Maarten E; Wang, Da-Neng

    2010-08-01

    LeuT is a member of the neurotransmitter/sodium symporter family, which includes the neuronal transporters for serotonin, norepinephrine, and dopamine. The original crystal structure of LeuT shows a primary leucine-binding site at the center of the protein. LeuT is inhibited by different classes of antidepressants that act as potent inhibitors of the serotonin transporter. The newly determined crystal structures of LeuT-antidepressant complexes provide opportunities to probe drug binding in the serotonin transporter, of which the exact position remains controversial. Structure of a LeuT-tryptophan complex shows an overlapping binding site with the primary substrate site. A secondary substrate binding site was recently identified, where the binding of a leucine triggers the cytoplasmic release of the primary substrate. This two binding site model presents opportunities for a better understanding of drug binding and the mechanism of inhibition for mammalian transporters.

  2. The Ethics of Sham Surgery on Research Subjects with Cognitivie Impairments that Affect Decision-Making Capacity

    PubMed Central

    Resnik, David B.; Miller, Frank

    2010-01-01

    Populations recruited to participate in sham surgery clinical trials sometimes include patients with cognitive impairments that affect decision-making capacity. In this commentary we examine arguments for and against including these patients in sham surgery clinical trials. We argue that patients with cognitive impairments that affect decision-making capacity should not be excluded from a sham surgery clinical trial if there are scientific reasons for including them in the study and basic ethical requirements for clinical research are met. PMID:20570755

  3. Decisional Capacity for Research Participation in Individuals with Mild Cognitive Impairment

    PubMed Central

    Jefferson, Angela L.; Lambe, Susan; Moser, David J.; Byerly, Laura K.; Ozonoff, Al; Karlawish, Jason H.

    2009-01-01

    OBJECTIVES To assess decisional capacity performance and the neuropsychological correlates of such performance to better understand higher-level instrumental activities of daily living in individuals with mild cognitive impairment (MCI). DESIGN Cross-sectional. SETTING Research center, medical center, or patient’s home. PARTICIPANTS Forty participants with MCI and 40 cognitively normal older controls (NCs) aged 60 to 90 (mean age ± standard deviation 73.3 ± 6.6; 54% female). MEASUREMENTS Capacity to provide informed consent for a hypothetical, but ecologically valid, clinical trial was assessed using the MacArthur Competence Assessment Tool for Clinical Research. Neuropsychological functioning was assessed using a comprehensive protocol. RESULTS Adjusted between-group comparisons yielded significant differences for most decisional capacity indices examined, including Understanding (P = .001; NC>MCI) and Reasoning (P = .002; NC>MCI). Post hoc analyses revealed that participants with MCI who were categorized as capable of providing informed consent according to expert raters had higher levels of education than those who were categorized as incapable. CONCLUSION The findings suggest that many individuals with MCI perform differently on a measure of decisional capacity than their NC peers and that participants with MCI who are incapable of providing informed consent on a hypothetical and complex clinical trial are less educated. These findings are consistent with prior studies documenting functional and financial skill difficulties in individuals with MCI. PMID:18482298

  4. Declining financial capacity in mild cognitive impairment: A 1-year longitudinal study.

    PubMed

    Triebel, K L; Martin, R; Griffith, H R; Marceaux, J; Okonkwo, O C; Harrell, L; Clark, D; Brockington, J; Bartolucci, A; Marson, Daniel C

    2009-09-22

    To investigate 1-year change in financial capacity in relation to conversion from amnestic mild cognitive impairment (MCI) to dementia. Seventy-six cognitively healthy older controls, 25 patients with amnestic MCI who converted to Alzheimer-type dementia during the study period (MCI converters), and 62 patients with MCI who did not convert to dementia (MCI nonconverters) were administered the Financial Capacity Instrument (FCI) at baseline and 1-year follow-up. Performance on the FCI domain and global scores was compared within and between groups using multivariate repeated-measures analyses. At baseline, controls performed better than MCI converters and nonconverters on almost all FCI domains and on both FCI total scores. MCI converters performed below nonconverters on domains of financial concepts, cash transactions, bank statement management, and bill payment and on both FCI total scores. At 1-year follow-up, MCI converters showed significantly greater decline than controls and MCI nonconverters for the domain of checkbook management and for both FCI total scores. The domain of bank statement management showed a strong trend. For both the checkbook and bank statement domains, MCI converters showed declines in procedural skills, such as calculating the correct balance in a checkbook register, but not in conceptual understanding of a checkbook or a bank statement. Declining financial skills are detectable in patients with mild cognitive impairment (MCI) in the year before their conversion to Alzheimer disease. Clinicians should proactively monitor patients with MCI for declining financial skills and advise patients and families about appropriate interventions.

  5. Capacity Limitations in Working Memory: The Impact on Lexical and Morphological Learning by Children with Language Impairment.

    ERIC Educational Resources Information Center

    Weismer, Susan Ellis

    1996-01-01

    This article examines the role of capacity limitations in working memory for children with specific language impairment (SLI). Preliminary findings support the contention that capacity constraints play a role in language disorders and that variations in the presentation rate of linguistic models affect the ability of children with SLI to learn new…

  6. Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging

    PubMed Central

    Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina

    2016-01-01

    Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways. PMID:26951333

  7. Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging.

    PubMed

    Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina; Morita, Yohei; Rudolph, Karl Lenhard

    2016-04-04

    Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways. © 2016 Tang et al.

  8. Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans

    PubMed Central

    Merritt, Edward K.; Stec, Michael J.; Thalacker-Mercer, Anna; Windham, Samuel T.; Cross, James M.; Shelley, David P.; Craig Tuggle, S.; Kosek, David J.; Kim, Jeong-su

    2013-01-01

    The regenerative response of skeletal muscle to mechanically induced damage is impaired with age. Previous work in our laboratory suggests this may result from higher proinflammatory signaling in aging muscle at rest and/or a greater inflammatory response to damage. We, therefore, assessed skeletal muscle proinflammatory signaling at rest and 24 h after unaccustomed, loaded knee extension contractions that induced modest muscle damage (72% increase in serum creatine kinase) in a cohort of 87 adults across three age groups (AGE40, AGE61, and AGE76). Vastus lateralis muscle gene expression and protein cell signaling of the IL-6 and TNF-α pathways were determined by quantitative PCR and immunoblot analysis. For in vitro studies, cell signaling and fusion capacities were compared among primary myoblasts from young (AGE28) and old (AGE64) donors treated with TNF-α. Muscle expression was higher (1.5- to 2.1-fold) in AGE76 and AGE61 relative to AGE40 for several genes involved in IL-6, TNF-α, and TNF-like weak inducer of apoptosis signaling. Indexes of activation for the proinflammatory transcription factors signal transducer and activator of transcription-3 and NF-κB were highest in AGE76. Resistance loading reduced gene expression of IL-6 receptor, muscle RING finger 1, and atrogin-1, and increased TNF-like weak inducer of apoptosis receptor expression. Donor myoblasts from AGE64 showed impaired differentiation and fusion in standard media and greater NF-κB activation in response to TNF-α treatment (compared with AGE28). We show for the first time that human aging is associated with muscle inflammation susceptibility (i.e., higher basal state of proinflammatory signaling) that is present in both tissue and isolated myogenic cells and likely contributes to the impaired regenerative capacity of skeletal muscle in the older population. PMID:23681911

  9. Glutamate Impairs Mitochondria Aerobic Respiration Capacity and Enhances Glycolysis in Cultured Rat Astrocytes.

    PubMed

    Yan, Xu; Shi, Zhong Fang; Xu, Li Xin; Li, Jia Xin; Wu, Min; Wang, Xiao Xuan; Jia, Mei; Dong, Li Ping; Yang, Shao Hua; Yuan, Fang

    2017-01-01

    To study the effect of glutamate on metabolism, shifts in glycolysis and lactate release in rat astrocytes. After 10 days, secondary cultured astrocytes were treated with 1 mmol/L glutamate for 1 h, and the oxygen consumption rates (OCR) and extra cellular acidification rate (ECAR) was analyzed using a Seahorse XF 24 Extracellular Flux Analyzer. Cell viability was then evaluated by MTT assay. Moreover, changes in extracellular lactate concentration induced by glutamate were tested with a lactate detection kit. Compared with the control group, treatment with 1 mmol/L glutamate decreased the astrocytes' maximal respiration and spare respiratory capacity but increased their glycolytic capacity and glycolytic reserve. Further analysis found that 1-h treatment with different concentrations of glutamate (0.1-1 mmol/L) increased lactate release from astrocytes, however the cell viability was not affected by the glutamate treatment. The current study provided direct evidence that exogenous glutamate treatment impaired the mitochondrial respiration capacity of astrocytes and enhanced aerobic glycolysis, which could be involved in glutamate injury or protection mechanisms in response to neurological disorders. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  10. Multidrug-resistance drug-binding peptides generated by using a phage display library.

    PubMed

    Popkov, M; Lussier, I; Medvedkine, V; Estève, P O; Alakhov, V; Mandeville, R

    1998-01-15

    A phage display library of random decapeptides was used to generate peptide ligands that can bind multidrug-resistance (MDR) drugs mimicking, in this respect, the drug-binding activity of P-glycoprotein. Seven peptide sequences were identified that specifically bound doxorubicin. Five of these sequences expressed the core consensus motif WXXW. The displacement assay showed that the phages expressing these peptides bound MDR type drugs (vinblastine, doxorubicin, verapamil, and genistein) with the same selectivity as P-glycoprotein and did not interact with non-MDR type drugs, such as arabinosylcytosine (Ara-C) and melphalan. One of the selected peptides that showed a highest capacity for the binding (VCDWWGWGIC) was synthesized and displayed competition with the phage for doxorubicin binding. The structure modeling suggested that all the selected sequences contained a hydrophobic envelope in which MDR drugs could be docked with substantial energy minimization. Western blot analysis showed that monospecific antibody obtained against the phage expressing VCDWWGWGIC peptide could specifically recognize P-glycoprotein in the membrane fraction of MDR phenotype MCF-7ADR cells. The MDR drug-binding sequences generated during this work could provide an important tool for design and screening of new chemotherapeutic agents.

  11. Clinical Interview Assessment of Financial Capacity in Older Adults with Mild Cognitive Impairment and Alzheimer’s Disease

    PubMed Central

    Marson, Daniel C.; Martin, Roy C.; Wadley, Virginia; Griffith, H. Randall; Snyder, Scott; Goode, Patricia S.; Kinney, F. Cleveland; Nicholas, Anthony P.; Steele, Terri; Anderson, Britt; Zamrini, Edward; Raman, Rema; Bartolucci, Alfred; Harrell, Lindy E.

    2009-01-01

    Objectives To investigate financial capacity in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using a clinician interview approach. Design Cross-sectional. Setting Tertiary care medical center. Participants Healthy older adults (N=75), patients with amnestic MCI (N=58), mild AD (N=97), and moderate AD (N=31). Measurements The investigators and five study physicians developed a conceptually based, semi-structured clinical interview for evaluating seven core financial domains and overall financial capacity (Semi-Structured Clinical Interview for Financial Capacity; SCIFC). For each participant, a physician made capacity judgments (capable, marginally capable, or incapable) for each financial domain and for overall capacity. Results Study physicians made a total of over 11,000 capacity judgments across the study sample (N=261). Very good inter-rater agreement was obtained for the SCIFC judgments. Increasing proportions of marginal and incapable judgment ratings were associated with increasing disease severity across the four study groups. For overall financial capacity, 95 percent of physician judgments for older controls were rated as capable, as compared to only 82% for patients with MCI, 26% for patients with mild AD, and 4% for patients with moderate AD. Conclusion Financial capacity in cognitively impaired older adults can be reliably evaluated by physicians using a relatively brief, semi-structured clinical interview. Financial capacity shows mild impairment in MCI, emerging global impairment in mild AD, and advanced global impairment in moderate AD. MCI patients and their families should proactively engage in financial and legal planning given these patients’ risk of developing AD and accelerated loss of financial abilities. PMID:19453308

  12. Age-related decline of autocrine pituitary adenylate cyclase-activating polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

    PubMed

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-06-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging.

  13. Age-Related Decline of Autocrine Pituitary Adenylate Cyclase-Activating Polypeptide Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells

    PubMed Central

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E.; Csiszar, Anna

    2015-01-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging. PMID:25136000

  14. Physiological responses to heat of resting man with impaired sweating capacity

    NASA Technical Reports Server (NTRS)

    Totel, G. L.

    1974-01-01

    The effects of total-body heat exposure were studied in three groups of subjects with varied degrees of impaired sweating capacity. The responses of two ectodermal dysplasic men, six quadriplegic men, and a man with widespread burned scar tissue were compared with the responses of three able-bodied men resting in the heat. It was found that the able-bodied and burned subjects competed successfully with a controlled environment of 38 C and 20% relative humidity for up to 150 min, whereas the quadriplegic and ectodermal dysplasic men developed hyperthermia, hyperventilation, and distress after only 120 and 75 min of heat exposure, respectively. The intolerance to heat is thus ascribed directly to the inability to produce and evaporate sweat.

  15. The impact of attentional allocation capacities on nonword repetition in children with specific language impairment.

    PubMed

    Leclercq, Anne-Lise; Maillart, Christelle; Lange, Manon; Majerus, Steve

    2015-01-01

    This study aimed at directly assessing the hypothesis that attentional allocation capacity influences poor nonword repetition (NWR) performances in children with specific language impairment (SLI), using an attention demanding visual search task given concurrently with the NWR task. Twenty-one children with SLI, 21 typically developing children matched on age and 21 typically developing children matched on nonword span performed an immediate serial recall task of nonwords. The nonword lists were presented either alone or concurrently with the visual search task. Overall, results revealed a resource-sharing trade-off between the two tasks. Children with SLI were affected to the same extent as their span-matched controls by the necessity to allocate their attentional resources between the two tasks. Interestingly, nonword processing strategies seemed to differ among groups: age-matched controls allocated a larger part of their attentional resources to the encoding stage, whereas nonword recall was more attention demanding in children with SLI and younger controls.

  16. A Study of Impairing Injuries in Real World Crashes Using the Injury Impairment Scale (IIS) and the Predicted Functional Capacity Index (PFCI-AIS)

    PubMed Central

    Barnes, Jo; Morris, Andrew

    2009-01-01

    The ability to predict impairment outcomes in large databases using a simplified technique allows researchers to focus attention on preventing costly impairing injuries. The dilemma that exists for researchers is to determine which method is the most reliable and valid. This study examines available methods to predict impairment and explores the differences between the IIS and pFCI applied to real world crash injury data. Occupant injury data from the UK Co-operative Crash Injury Study (CCIS) database have been coded using AIS 1990 and AIS 2005. The data have subsequently been recoded using the associated impairment scales namely the Injury Impairment Scale (IIS) and the predicted Functional Capacity Index (pFCI) to determine the predicted impairment levels of injuries at one year post crash. Comparisons between the levels of impairment were made and any differences further explored. Injury data for the period February 2006 to September 2008 from the CCIS database were used in the analysis which involved a dataset of 2,437 occcupants who sustained over 8000 injuries. This study found some differences between the impairment scales for injuries coded to the AIS 1990 and AIS 2005 coding dictionaries. The pFCI predicts 31.5% of injuries to be impairing in AIS 2005, less than the IIS (38.5%) using AIS 1990. Using CCIS data the pFCI predicted that only 6% of the occupants with a coded injury would have an impairing injury compared to 24% of occupants using the IIS. The main body regions identified as having the major differences between the two impairment scales for car occupants were the head and spine. Follow up data were then used for a small number of cases (n=31, lower extremity and whiplash injuries) to examine any differences in predicted impairment versus perceived impairment. These data were selected from a previous study conducted between 2003 and 2006 and identified the discrepancy between predicted impairment and actual perceived impairment as defined by the

  17. A study of impairing injuries in real world crashes using the Injury Impairment Scale (IIS) and the predicted Functional Capacity Index (PFCI-AIS).

    PubMed

    Barnes, Jo; Morris, Andrew

    2009-10-01

    The ability to predict impairment outcomes in large databases using a simplified technique allows researchers to focus attention on preventing costly impairing injuries. The dilemma that exists for researchers is to determine which method is the most reliable and valid. This study examines available methods to predict impairment and explores the differences between the IIS and pFCI applied to real world crash injury data. Occupant injury data from the UK Co-operative Crash Injury Study (CCIS) database have been coded using AIS 1990 and AIS 2005. The data have subsequently been recoded using the associated impairment scales namely the Injury Impairment Scale (IIS) and the predicted Functional Capacity Index (pFCI) to determine the predicted impairment levels of injuries at one year post crash. Comparisons between the levels of impairment were made and any differences further explored. Injury data for the period February 2006 to September 2008 from the CCIS database were used in the analysis which involved a dataset of 2,437 occcupants who sustained over 8000 injuries. This study found some differences between the impairment scales for injuries coded to the AIS 1990 and AIS 2005 coding dictionaries. The pFCI predicts 31.5% of injuries to be impairing in AIS 2005, less than the IIS (38.5%) using AIS 1990. Using CCIS data the pFCI predicted that only 6% of the occupants with a coded injury would have an impairing injury compared to 24% of occupants using the IIS. The main body regions identified as having the major differences between the two impairment scales for car occupants were the head and spine. Follow up data were then used for a small number of cases (n=31, lower extremity and whiplash injuries) to examine any differences in predicted impairment versus perceived impairment. These data were selected from a previous study conducted between 2003 and 2006 and identified the discrepancy between predicted impairment and actual perceived impairment as defined by the

  18. Cognitive models of medical decision-making capacity in patients with mild cognitive impairment.

    PubMed

    Okonkwo, O C; Griffith, H R; Belue, K; Lanza, S; Zamrini, E Y; Harrell, L E; Brockington, J C; Clark, D; Raman, R; Marson, D C

    2008-03-01

    This study investigated cognitive predictors of medical decision-making capacity (MDC) in patients with amnestic mild cognitive impairment (MCI). A total of 56 healthy controls, 60 patients with MCI, and 31 patients with mild Alzheimer's disease (AD) were administered the Capacity to Consent to Treatment Instrument (CCTI) and a neuropsychological test battery. The CCTI assesses MDC across four established treatment consent standards--S1 (expressing choice), S3 (appreciation), S4 (reasoning), and S5 (understanding)--and one experimental standard [S2] (reasonable choice). Scores on neuropsychological measures were correlated with scores on each CCTI standard. Significant bivariate correlates were subsequently entered into stepwise regression analyses to identity group-specific multivariable predictors of MDC across CCTI standards. Different multivariable cognitive models emerged across groups and consent standards. For the MCI group, measures of short-term verbal memory were key predictors of MDC for each of the three clinically relevant standards (S3, S4, and S5). Secondary predictors were measures of executive function. In contrast, in the mild AD group, measures tapping executive function and processing speed were primary predictors of S3, S4, and S5. MDC in patients with MCI is supported primarily by short-term verbal memory. The findings demonstrate the impact of amnestic deficits on MDC in patients with MCI.

  19. Fast growth may impair regeneration capacity in the branching coral Acropora muricata.

    PubMed

    Denis, Vianney; Guillaume, Mireille M M; Goutx, Madeleine; de Palmas, Stéphane; Debreuil, Julien; Baker, Andrew C; Boonstra, Roxane K; Bruggemann, J Henrich

    2013-01-01

    Regeneration of artificially induced lesions was monitored in nubbins of the branching coral Acropora muricata at two reef-flat sites representing contrasting environments at Réunion Island (21°07'S, 55°32'E). Growth of these injured nubbins was examined in parallel, and compared to controls. Biochemical compositions of the holobiont and the zooxanthellae density were determined at the onset of the experiment, and the photosynthetic efficiency (Fv/Fm ) of zooxanthellae was monitored during the experiment. Acropora muricata rapidly regenerated small lesions, but regeneration rates significantly differed between sites. At the sheltered site characterized by high temperatures, temperature variations, and irradiance levels, regeneration took 192 days on average. At the exposed site, characterized by steadier temperatures and lower irradiation, nubbins demonstrated fast lesion repair (81 days), slower growth, lower zooxanthellae density, chlorophyll a concentration and lipid content than at the former site. A trade-off between growth and regeneration rates was evident here. High growth rates seem to impair regeneration capacity. We show that environmental conditions conducive to high zooxanthellae densities in corals are related to fast skeletal growth but also to reduced lesion regeneration rates. We hypothesize that a lowered regenerative capacity may be related to limited availability of energetic and cellular resources, consequences of coral holobionts operating at high levels of photosynthesis and associated growth.

  20. Impaired Adipose Tissue Expandability and Lipogenic Capacities as Ones of the Main Causes of Metabolic Disorders

    PubMed Central

    Tinahones, Francisco José

    2015-01-01

    Obesity is considered a major health problem. However, mechanisms involved and its comorbidities are not elucidated. Recent theories concerning the causes of obesity have focused on a limit to the functional capacity of adipose tissue, comparing it with other vital organs. This assumption has been the central point of interest in our laboratory. We proposed that the failure of adipose tissue is initiated by the difficulty of this tissue to increase its cellularity due to excess in fat contribution, owing to genetic or environmental factors. Nevertheless, why the adipose tissue reduces its capacity to make new adipocytes via mesenchymal cells of the stroma has not yet been elucidated. Thus, we suggest that this tissue ceases fulfilling its main function, the storage of excess fat, thereby affecting some of the key factors involved in lipogenesis, some of which are reviewed in this paper (PPARγ, ROR1, FASN, SCD1, Rab18, BrCa1, ZAG, and FABP4). On the other hand, mechanisms involved in adipose tissue expandability are also impaired, predominating hypertrophy via an increase in apoptosis and a decrease in adipogenesis and angiogenesis. However, adipose tissue failure is only part of this great orchestra, only a chapter of this nightmare. PMID:25922847

  1. Financial capacity of older African Americans with amnestic mild cognitive impairment.

    PubMed

    Triebel, Kristen L; Okonkwo, Ozioma C; Martin, Roy; Griffith, Henry Randall; Crowther, Martha; Marson, Daniel C

    2010-01-01

    This study investigated financial abilities of 154 patients with mild cognitive impairment (MCI) (116 white, 38 African American) using the Financial Capacity Instrument (FCI). In a series of linear regression models, we examined the effect of race on FCI performance and identified preliminary predictor variables that mediated observed racial differences on the FCI. Prior/premorbid abilities were identified. Predictor variables examined in the models included race and other demographic factors (age, education, sex), performance on global cognitive measures (MMSE, DRS-2 Total Score), history of cardiovascular disease (hypertension, diabetes, hypercholesterolemia), and a measure of educational achievement (WRAT-3 Arithmetic). African American patients with MCI performed below white patients with MCI on 6 of the 7 FCI domains examined and on the FCI total score. WRAT-3 Arithmetic emerged as a partial mediator of group differences on the FCI, accounting for 54% of variance. In contrast, performance on global cognitive measures and history of cardiovascular disease only accounted for 14% and 2%, respectively, of the variance. Racial disparities in financial capacity seem to exist among patients with amnestic MCI. Basic academic math skills related to educational opportunity and quality of education account for a substantial proportion of the group difference in financial performance.

  2. Sentence Repetition Accuracy in Adults With Developmental Language Impairment: Interactions of Participant Capacities and Sentence Structures

    PubMed Central

    Miller, Carol A.; van Hell, Janet G.

    2016-01-01

    Purpose We asked whether sentence repetition accuracy could be explained by interactions of participant processing limitations with the structures of the sentences. We also tested a prediction of the procedural deficit hypothesis (Ullman & Pierpont, 2005) that adjuncts are more difficult than arguments for individuals with developmental language impairment (DLI). Method Forty-four young adults participated, 21 with DLI. The sentence repetition task varied sentence length and the use of arguments and adjuncts. We also administered measures of working memory and processing speed. Our regression models focused on these interactions: group and argument status; processing speed, length, and argument status; and working memory capacity, length, and argument status. Results Language ability group was a significant predictor of sentence repetition accuracy but did not interact with argument status. Processing speed interacted with sentence length and argument status. Working memory capacity and its separate interactions with argument status and sentence length predicted sentence repetition accuracy. Conclusions Many adults with DLI may have difficulty with adjuncts as a result of their working memory limitations rather than their language ability. Cognitive limitations common to individuals with DLI are revealed more by particular sentence structures, suggesting ways to construct more diagnostically accurate sentence repetition tasks. PMID:27272196

  3. Fast Growth May Impair Regeneration Capacity in the Branching Coral Acropora muricata

    PubMed Central

    Denis, Vianney; Guillaume, Mireille M. M.; Goutx, Madeleine; de Palmas, Stéphane; Debreuil, Julien; Baker, Andrew C.; Boonstra, Roxane K.; Bruggemann, J. Henrich

    2013-01-01

    Regeneration of artificially induced lesions was monitored in nubbins of the branching coral Acropora muricata at two reef-flat sites representing contrasting environments at Réunion Island (21°07′S, 55°32′E). Growth of these injured nubbins was examined in parallel, and compared to controls. Biochemical compositions of the holobiont and the zooxanthellae density were determined at the onset of the experiment, and the photosynthetic efficiency (Fv/Fm) of zooxanthellae was monitored during the experiment. Acropora muricata rapidly regenerated small lesions, but regeneration rates significantly differed between sites. At the sheltered site characterized by high temperatures, temperature variations, and irradiance levels, regeneration took 192 days on average. At the exposed site, characterized by steadier temperatures and lower irradiation, nubbins demonstrated fast lesion repair (81 days), slower growth, lower zooxanthellae density, chlorophyll a concentration and lipid content than at the former site. A trade-off between growth and regeneration rates was evident here. High growth rates seem to impair regeneration capacity. We show that environmental conditions conducive to high zooxanthellae densities in corals are related to fast skeletal growth but also to reduced lesion regeneration rates. We hypothesize that a lowered regenerative capacity may be related to limited availability of energetic and cellular resources, consequences of coral holobionts operating at high levels of photosynthesis and associated growth. PMID:24023627

  4. Sentence Repetition Accuracy in Adults With Developmental Language Impairment: Interactions of Participant Capacities and Sentence Structures.

    PubMed

    Poll, Gerard H; Miller, Carol A; van Hell, Janet G

    2016-04-01

    We asked whether sentence repetition accuracy could be explained by interactions of participant processing limitations with the structures of the sentences. We also tested a prediction of the procedural deficit hypothesis (Ullman & Pierpont, 2005) that adjuncts are more difficult than arguments for individuals with developmental language impairment (DLI). Forty-four young adults participated, 21 with DLI. The sentence repetition task varied sentence length and the use of arguments and adjuncts. We also administered measures of working memory and processing speed. Our regression models focused on these interactions: group and argument status; processing speed, length, and argument status; and working memory capacity, length, and argument status. Language ability group was a significant predictor of sentence repetition accuracy but did not interact with argument status. Processing speed interacted with sentence length and argument status. Working memory capacity and its separate interactions with argument status and sentence length predicted sentence repetition accuracy. Many adults with DLI may have difficulty with adjuncts as a result of their working memory limitations rather than their language ability. Cognitive limitations common to individuals with DLI are revealed more by particular sentence structures, suggesting ways to construct more diagnostically accurate sentence repetition tasks.

  5. Impaired aerobic exercise capacity and cardiac autonomic control in primary antiphospholipid syndrome.

    PubMed

    Garcia, C B; Perandini, L A; Seguro, L P C; Gualano, B; Roschel, H; Bonfa, E; Borba, E F; Sá-Pinto, A L

    2013-08-01

    Primary antiphospholipid syndrome (PAPS) is associated with increased risk of cardiovascular disease and mortality. Aerobic capacity and cardiac autonomic control are also associated with these risks. The aim of our study was to assess aerobic capacity and cardiac autonomic control in PAPS patients. Thirteen women with PAPS and 13 healthy controls matched for age, gender, and body mass index were enrolled for the study. Both groups were sedentary and were not under chronotropic, antidepressants and hypolipemiant drugs. All subjects performed a treadmill-graded maximal exercise. Aerobic capacity was assessed by peak oxygen uptake (VO2peak), time at anaerobic ventilatory threshold (VAT) and respiratory compensation point (RCP) and time-to-exhaustion, whereas cardiac autonomic control was assessed by chronotropic reserve (CR) and heart rate recovery at the first and second minutes after graded exercise (HRR1min and HRR2min, respectively). All aerobic capacity indexes were reduced more in PAPS patients than in healthy subjects: VO2peak (30.2 ± 4.7 vs 34.6 ± 4.3 ml.kg(-1).min(-1), p = 0.021), time at VAT (3.0 ± 1.5 vs 5.0 ± 2.0 min, p = 0.016), time at RCP (6.5 ± 2.0 vs 8.0 ± 2.0 min, p = 0.050), time-to-exhaustion (8.5 ± 2.0 vs 11.0 ± 2.5 min, p = 0.010). HRR1min (22 ± 9 vs 30 ± 7 bpm, p = 0.032) and HRR2min (33 ± 9 vs 46 ± 8 bpm, p = 0.002) were delayed in PAPS patients compared to healthy controls but CR was not significantly different (p = 0.272). In conclusion, an impaired aerobic capacity and cardiac autonomic control was identified in PAPS.

  6. Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

    PubMed

    Murray, Brendan G; Davies, Don A; Molder, Joel J; Howland, John G

    2017-05-01

    Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Impaired exercise capacity and skeletal muscle function in a mouse model of pulmonary inflammation

    PubMed Central

    Tang, Kechun; Murano, George; Wagner, Harrieth; Nogueira, Leonardo; Wagner, Peter D.; Tang, Alisa; Dalton, Nancy D.; Gu, Yusu; Peterson, Kirk L.

    2013-01-01

    Pulmonary TNFα has been linked to reduced exercise capacity in a subset of patients with moderate to severe chronic obstructive pulmonary disease (COPD). We hypothesized that prolonged, high expression of pulmonary TNFα impairs cardiac and skeletal muscle function, and both contribute to exercise limitation. Using a surfactant protein C promoter-TNFα construct, TNFα was overexpressed throughout life in mouse lungs (SP-C/TNFα+). TNFα levels in wild-type (WT) female serum and lung were two- and threefold higher than in WT male mice. In SP-C/TNFα+ mice, TNFα increased similarly in both sexes. Treadmill exercise was impaired only in male SP-C/TNFα+ mice. While increases in lung volume and airspace size induced by TNFα were comparable in both sexes, pulmonary hypertension along with lower body and muscle mass were evident only in male mice. Left ventricular (LV) function (cardiac output, stroke volume, LV maximal pressure, and LV maximal pressure dP/dt) was not altered by TNFα overexpression. Fatigue measured in isolated soleus and EDL was more rapid only in soleus of male SP-C/TNFα+ mice and accompanied by a loss of oxidative IIa fibers, citrate synthase activity, and PGC-1α mRNA and increase in atrogin-1 and MuRF1 expression also only in male mice. In situ gastrocnemius fatigue resistance, reflecting both oxygen availability and contractility, was decreased similarly in female and male SP-C/TNFα+ mice. These data indicate that male, but not female, mice overexpressing pulmonary TNFα are susceptible to exercise limitation, possibly due to muscle wasting and loss of the oxidative muscle phenotype, with protection in females possibly due to estrogen. PMID:23449936

  8. Subclinical zinc deficiency impairs pancreatic digestive enzyme activity and digestive capacity of weaned piglets.

    PubMed

    Brugger, Daniel; Windisch, Wilhelm M

    2016-08-01

    This study investigated the effects of short-term subclinical Zn deficiency on exocrine pancreatic activity and changes in digestive capacity. A total of forty-eight weaned piglets were fed ad libitum a basal diet (maize and soyabean meal) with adequate Zn supply (88 mg Zn/kg diet) during a 2-week acclimatisation phase. Animals were then assigned to eight dietary treatment groups (n 6) according to a complete randomised block design considering litter, live weight and sex. All pigs were fed restrictively (450 g diet/d) the basal diet but with varying ZnSO4.7H2O additions, resulting in 28·1, 33·6, 38·8, 42·7, 47·5, 58·2, 67·8 and 88·0 mg Zn/kg diet for a total experimental period of 8 d. Pancreatic Zn concentrations and pancreatic activities of trypsin, chymotrypsin, carboxypeptidase A and B, elastase and α-amylase exhibited a broken-line response to stepwise reduction in dietary Zn by declining beneath thresholds of 39·0, 58·0, 58·0, 41·2, 47·5, 57·7 and 58·0 mg Zn/kg diet, respectively. Furthermore, carboxypeptidase B and α-amylase activities were significantly lower in samples with reduced pancreatic Zn contents. Coefficients of faecal digestibility of DM, crude protein, total lipids and crude ash responded similarly to pancreatic enzyme activities by declining below dietary thresholds of 54·7, 45·0, 46·9 and 58·2 mg Zn/kg diet, respectively. In conclusion, (1) subclinical Zn deficiency impaired pancreatic exocrine enzymes, (2) this response was connected to pancreatic Zn metabolism and (3) the decline in catalytic activity impaired faecal digestibility already after 1 week of insufficient alimentary Zn supply and very early before clinical deficiency symptoms arise.

  9. Impaired cholesterol efflux capacity and vasculoprotective function of high-density lipoprotein in heart transplant recipients.

    PubMed

    Singh, Neha; Jacobs, Frank; Rader, Daniel J; Vanhaecke, Johan; Van Cleemput, Johan; De Geest, Bart

    2014-05-01

    High-density lipoprotein (HDL) metabolism is significantly altered in heart transplant recipients. We hypothesized that HDL function may be impaired in these patients. Fifty-two patients undergoing coronary angiography between 5 and 15 years after heart transplantation were recruited in this cross-sectional study. Cholesterol efflux capacity of apolipoprotein B-depleted plasma was analyzed using a validated assay. The vasculoprotective function of HDL was studied by means of an endothelial progenitor cell migration assay. HDL cholesterol levels were similar in heart transplant patients compared with healthy controls. However, normalized cholesterol efflux and vasculoprotective function were reduced by 24.1% (p < 0.001) and 27.0% (p < 0.01), respectively, in heart transplant recipients compared with healthy controls. HDL function was similar in patients with and without cardiac allograft vasculopathy (CAV) and was not related to C-reactive protein (CRP) levels. An interaction effect (p = 0.0584) was observed between etiology of heart failure before transplantation and steroid use as factors of HDL cholesterol levels. Lower HDL cholesterol levels occurred in patients with prior ischemic cardiomyopathy who were not taking steroids. However, HDL function was independent of the etiology of heart failure before transplantation and steroid use. The percentage of patients with a CRP level ≥6 mg/liter was 3.92-fold (p < 0.01) higher in patients with CAV than in patients without CAV. HDL function is impaired in heart transplant recipients, but it is unrelated to CAV status. The proportion of patients with a CRP level ≥6 mg/liter is prominently higher in CAV-positive patients. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Structure and localisation of drug binding sites on neurotransmitter transporters.

    PubMed

    Ravna, Aina W; Sylte, Ingebrigt; Dahl, Svein G

    2009-10-01

    The dopamine (DAT), serotontin (SERT) and noradrenalin (NET) transporters are molecular targets for different classes of psychotropic drugs. The crystal structure of Aquifex aeolicus LeuT(Aa) was used as a template for molecular modeling of DAT, SERT and NET, and two putative drug binding sites (pocket 1 and 2) in each transporter were identified. Cocaine was docked into binding pocket 1 of DAT, corresponding to the leucine binding site in LeuT(Aa), which involved transmembrane helices (TMHs) 1, 3, 6 and 8. Clomipramine was docked into binding pocket 2 of DAT, involving TMHs 1, 3, 6, 10 and 11, and extracellular loops 4 and 6, corresponding to the clomipramine binding site in a crystal structure of a LeuT(Aa)-clomipramine complex. The structures of the proposed cocaine- and tricyclic antidepressant-binding sites may be of particular interest for the design of novel DAT interacting ligands.

  11. Impaired colony-forming capacity of circulating endothelial progenitor cells in patients with emphysema.

    PubMed

    Kim, Eun-Kyung; Lee, Ji-Hyun; Jeong, Hye-Cheol; Oh, Doyeon; Hwang, Seong-Gyu; Cho, Yong-Wook; Lee, Seon-Ju; Oh, Yeon-Mok; Lee, Sang-Do

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is classified into emphysema and chronic bronchitis, which are thought to result from different pathophysiological pathways. Smoking-induced lung parenchymal destruction and inadequate repair are involved in the pathogenesis of emphysema. In addition, decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis in the lung may participate in emphysema pathogenesis. As stem cells, circulating endothelial progenitor cells (EPCs) may play a key role in the maintenance of vascular integrity by replacing and repairing the damaged endothelial cells in the tissues. To determine whether the lack of appropriate repair by circulating EPCs in cases of smoking-induced endothelial cell injury participates in emphysema pathogenesis, we determined the association between the colony-forming or migratory capacity of circulating EPCs and the presence of emphysema in 51 patients with COPD. The patients were divided into emphysema (n = 23) and non-emphysema groups (n = 28) based on high-resolution computed tomography. Twenty-two smokers with normal lung function and 14 normal non-smokers served as controls. Circulating EPCs isolated from patients with emphysema showed significantly lower colony-forming units (CFUs) than those from patients with non-emphysema group, smokers with normal lung function, and normal non-smokers. EPCs from patients with emphysema showed significantly lower migratory capacity than those from normal non-smoking controls (p < 0.05). On multivariate analysis, the EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903-0.987, p = 0.011). Thus, impaired functions of circulating EPCs may contribute to the development of emphysema.

  12. Sentence Comprehension in Specific Language Impairment: A Task Designed to Distinguish between Cognitive Capacity and Syntactic Complexity

    ERIC Educational Resources Information Center

    Leonard, Laurence B.; Deevy, Patricia; Fey, Marc E.; Bredin-Oja, Shelley L.

    2013-01-01

    Purpose: This study examined sentence comprehension in children with specific language impairment (SLI) in a manner designed to separate the contribution of cognitive capacity from the effects of syntactic structure. Method: Nineteen children with SLI, 19 typically developing children matched for age (TD-A), and 19 younger typically developing…

  13. Sentence Comprehension in Specific Language Impairment: A Task Designed to Distinguish between Cognitive Capacity and Syntactic Complexity

    ERIC Educational Resources Information Center

    Leonard, Laurence B.; Deevy, Patricia; Fey, Marc E.; Bredin-Oja, Shelley L.

    2013-01-01

    Purpose: This study examined sentence comprehension in children with specific language impairment (SLI) in a manner designed to separate the contribution of cognitive capacity from the effects of syntactic structure. Method: Nineteen children with SLI, 19 typically developing children matched for age (TD-A), and 19 younger typically developing…

  14. Working Memory Capacity and Its Relation to Stroop Interference and Facilitation Effects in Individuals with Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Sung, Jee Eun; Kim, Jin Hee; Jeong, Jee Hyang; Kang, Heejin

    2012-01-01

    Purpose: The purposes of the study were to investigate (a) the task-specific differences in short-term memory (STM) and working memory capacity (WMC) in individuals with mild cognitive impairment (MCI) and normal elderly adults (NEAs), (b) the Stroop interference and facilitation effects, and (c) the relationship of STM and WMC to the Stroop…

  15. Ischemia Reperfusion Unveils Impaired Capacity of Older Adults to Restrain Oxidative Insult

    PubMed Central

    Davies, Sean S.; Traustadóttir, Tinna; Stock, Anthoney A.; Ye, Fei; Shyr, Yu; Harman, S. Mitchell; Roberts, L. Jackson

    2009-01-01

    Age independently predicts poor outcome in a variety of medical settings including sepsis, trauma, severe burns, and surgery. Since these conditions are associated with oxidative stress, we hypothesized that the capacity to constrain oxidative insult diminishes with age, leading to more extensive oxidative damage during trauma. To test this hypothesis, we used supra-systolic inflation of an arm blood pressure cuff to safely induce localized forearm ischemia/reperfusion (I/R) and quantified plasma F2-isoprostane (IsoP) levels in serial blood samples. Prior to I/R, IsoP levels were similar in young (20-33 yrs) and older adults (62-81 yrs). After I/R challenge, the magnitude and duration of increased IsoP levels was significantly greater in older adults. Because aging is associated with declining levels of sex hormones that contribute to regulation of antioxidant enzyme expression, we then examined the response to I/R in older women receiving hormone replacement therapy, and found these women did not manifest the amplified IsoP response found in untreated older women. These finding demonstrate that aging impairs the ability to restrain oxidative damage after an acute insult, which may contribute to the increased vulnerability of older adults to traumatic conditions, and establishes a useful method to identify effective interventions to ameliorate this deficiency. PMID:19596063

  16. Impaired secondary oxidant deactivation capacity and enhanced oxidative stress in serum from alveld affected lambs.

    PubMed

    Hegge, Anne Bee; Mysterud, Ivar; Karlsen, Jan; Skulberg, Olav M; Laane, Carl M M; Schumacher, Trond; Tønnesen, Hanne Hjorth

    2013-09-05

    Alveld is a hepatogenous photosensitivity disorder in lambs. The aim of the study was to investigate if alveld affected lambs had a reduced capacity to handle oxidative stress induced from either endogenous and/or exogenous photosensitizers. Serum samples from alveld lambs (n=33) were compared to serum samples from control lambs (n=31) and exposed to a controlled amount of singlet oxygen ((1)O2). The sera from alveld lambs were found to have an impaired ability to deactivate reactive oxygen species (ROS) compared to control sera. A higher degree of initial hemolysis and a higher concentration of the exogenous photosensitizer phytoporphyrin (PP) were detected in alveld sera compared to the controls. The action spectrum for the formation of (1)O2 indicated that PP as well as the endogenous compound protoporphyrin IX (PP IX) may act as in vivo photosensitizers. A relatively high level of iron was detected in pooled serum from alveld lambs that showed a high degree of hemolysis. It was concluded that alveld photosensitivity is likely to be initiated by a photodynamic reaction involving PP and possibly also PP IX followed by a light-independent reaction involving hemoglobin-related products and catalysis by the Fenton reaction. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Functional Capacity, Muscle Fat Infiltration, Power Output, and Cognitive Impairment in Institutionalized Frail Oldest Old

    PubMed Central

    Casas-Herrero, Alvaro; Cadore, Eduardo L.; Zambom-Ferraresi, Fabricio; Idoate, Fernando; Millor, Nora; Martínez-Ramirez, Alicia; Gómez, Marisol; Rodriguez-Mañas, Leocadio; Marcellán, Teresa; de Gordoa, Ana Ruiz; Marques, Mário C.

    2013-01-01

    Abstract This study examined the neuromuscular and functional performance differences between frail oldest old with and without mild cognitive impairment (MCI). In addition, the associations between functional capacities, muscle mass, strength, and power output of the leg muscles were also examined. Forty-three elderly men and women (91.9±4.1 years) were classified into three groups—the frail group, the frail with MCI group (frail+MCI), and the non-frail group. Strength tests were performed for upper and lower limbs. Functional tests included 5-meter habitual gait, timed up-and-go (TUG), dual task performance, balance, and rise from a chair ability. Incidence of falls was assessed using questionnaires. The thigh muscle mass and attenuation were assessed using computed tomography. There were no differences between the frail and frail+MCI groups for all the functional variables analyzed, except in the cognitive score of the TUG with verbal task, which frail showed greater performance than the frail+MCI group. Significant associations were observed between the functional performance, incidence of falls, muscle mass, strength, and power in the frail and frail+MCI groups (r=−0.73 to r=0.83, p<0.01 to p<0.05). These results suggest that the frail oldest old with and without MCI have similar functional and neuromuscular outcomes. Furthermore, the functional outcomes and incidences of falls are associated with muscle mass, strength, and power in the frail elderly population. PMID:23822577

  18. Relationship between ambulatory capacity and cardiorespiratory fitness in chronic stroke: Influence of stroke-specific impairments

    PubMed Central

    Pang, Marco YC; Eng, Janice J; Dawson, Andrew S

    2016-01-01

    Study Objectives To identify in individuals with chronic stroke (1) the relationship between the maximal oxygen uptake (VO2max) during cycle ergometry and the distance covered in the Six Minute Walk Test (6MWT), and (2) the stroke-specific impairments which are important determinants for the 6MWT distance. Design Cross-sectional study using a convenience sample. Setting Exercise testing laboratory in a tertiary rehabilitation center. Participants Sixty-three older adults (mean age ± standard deviation, 65.3 ± 8.7) with an average post-stroke interval of 5.5 ± 4.9 years. Intervention Not applicable Main Outcome Measures Each subject underwent a maximal cycle ergometer test and a 6MWT. Oxygen consumption (VO2) was measured during both tests. Subjects were also evaluated for Berg Balance Scale, Modified Ashworth Scale of Spasticity, isometric knee extension strength and percent body fat. Results The 6MW distance had a low correlation with the VO2max (r=0.402). Balance, knee extension strength and spasticity were all significant determinants for the 6MWT distance, with balance being the major contributor for the 6MWT distance, accounting for 66.5% of its variance. Conclusions Factors other than the cardiorespiratory status considerably influenced the ambulatory capacity as measured by the 6MWT. The 6MWT distance alone should not be used to indicate cardiorespiratory fitness in individuals with chronic stroke. PMID:15705987

  19. XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells

    PubMed Central

    Moreno-Martínez, Daniel; Nomdedeu, Meritxell; Lara-Castillo, María Carmen; Etxabe, Amaia; Pratcorona, Marta; Tesi, Niccolò; Díaz-Beyá, Marina; Rozman, María; Montserrat, Emili; Urbano-Ispizua, Álvaro; Esteve, Jordi; Risueño, Ruth M.

    2014-01-01

    Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials. PMID:24952669

  20. Recovery of Percent Vital Capacity by Breathing Training in Patients With Panic Disorder and Impaired Diaphragmatic Breathing.

    PubMed

    Yamada, Tatsuji; Inoue, Akiomi; Mafune, Kosuke; Hiro, Hisanori; Nagata, Shoji

    2017-09-01

    Slow diaphragmatic breathing is one of the therapeutic methods used in behavioral therapy for panic disorder. In practice, we have noticed that some of these patients could not perform diaphragmatic breathing and their percent vital capacity was initially reduced but could be recovered through breathing training. We conducted a comparative study with healthy controls to investigate the relationship between diaphragmatic breathing ability and percent vital capacity in patients with panic disorder. Our findings suggest that percent vital capacity in patients with impaired diaphragmatic breathing was significantly reduced compared with those with normal diaphragmatic breathing and that diaphragmatic breathing could be restored by breathing training. Percent vital capacity of the healthy controls was equivalent to that of the patients who had completed breathing training. This article provides preliminary findings regarding reduced vital capacity in relation to abnormal respiratory movements found in patients with panic disorder, potentially offering alternative perspectives for verifying the significance of breathing training for panic disorder.

  1. Association of TNF-α with Impaired Migration Capacity of Mesenchymal Stem Cells in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Li, Xia; Feng, Xuebing; Zhang, Jiyun; Chen, Jinyun; Liu, Rui; Chen, Haifeng; Sun, Lingyun

    2014-01-01

    Previous studies indicated that bone marrow mesenchymal stem cells (BMSCs) from patients with systemic lupus erythematosus (SLE) exhibited impaired capacities of proliferation, differentiation, and immune modulation. Considering that migration capacity is important for the exertion of BMSCs functions, the defects in migration might contribute to BMSCs dysfunction in SLE patients. In this study, we showed that the migration capacity of SLE BMSCs was remarkably impaired in comparison with those of healthy controls. Increased tumor necrosis factor α (TNF-α) in SLE serum significantly inhibited the migration capacity and in vivo homing capacity of SLE BMSCs via a specific TNF receptor I (TNFRI) manner, in which decreased HGF mRNA production caused by the activation of I kappa B kinase beta (IKK-β) pathway is partially involved. To our knowledge, this is the first report to discuss the possible mechanisms for impaired migration of BMSCs in SLE patients. Our results suggest that inhibition of TNF-α pathway might be helpful for accelerating BMSCs migration to the inflammatory microenvironment in SLE patients, thereby having a potential role in SLE treatment. PMID:25762184

  2. Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin.

    PubMed

    Ashrafi-Kooshk, Mohammad Reza; Ebrahimi, Farangis; Ranjbar, Samira; Ghobadi, Sirous; Moradi, Nastaran; Khodarahmi, Reza

    2015-09-01

    Human serum albumin (HSA), the most abundant protein in blood plasma, is a monomeric multidomain protein that possesses an extraordinary capacity for binding, so that serves as a circulating depot for endogenous and exogenous compounds. During the heat sterilization process, the structure of pharmaceutical-grade HSA may change and some of its activities may be lost. In this study, to provide deeper insight on this issue, we investigated drug-binding and some physicochemical properties of purified albumin (PA) and pharmaceutical-grade albumin (PGA) using two known drugs (indomethacin and ibuprofen). PGA displayed significantly lower drug binding capacity compared to PA. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between the drugs and the proteins are different from each other. Surface hydrophobicity as well as the stability of PGA decreased compared to PA, also surface hydrophobicity of PA and PGA increased upon drugs binding. Also, kinetic analysis of pseudo-esterase activities indicated that Km and Vmax parameters for PGA enzymatic activity are more and less than those of PA, respectively. This in vitro study demonstrates that the specific drug binding of PGA is significantly reduced. Such studies can act as connecting bridge between basic research discoveries and clinical applications.

  3. Reading skills in young adolescents with a history of Specific Language Impairment: The role of early semantic capacity.

    PubMed

    Buil-Legaz, Lucía; Aguilar-Mediavilla, Eva; Rodríguez-Ferreiro, Javier

    2015-01-01

    This study assessed the reading skills of 19 Spanish-Catalan children with Specific Language Impairment (SLI) and 16 age-matched control children. Children with SLI have difficulties with oral language comprehension, which may affect later reading acquisition. We conducted a longitudinal study examining reading acquisition in these children between 8 and 12 years old and we relate this data with early oral language acquisition at 6 years old. Compared to the control group, the SLI group presented impaired decoding and comprehension skills at age 8, as evidenced by poor scores in all the assessed tasks. Nevertheless, only text comprehension abilities appeared to be impaired at age 12. Individual analyses confirmed the presence of comprehension deficits in most of the SLI children. Furthermore, early semantic verbal fluency at age 6 appeared to significantly predict the reading comprehension capacity of SLI participants at age 12. Our results emphasize the importance of semantic capacity at early stages of oral language development over the consolidation of reading acquisition at later stages. Readers will recognize the relevance of prior oral language impairment, especially semantic capacity, in children with a history of SLI as a risk factor for the development of later reading difficulties. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Neurocognitive predictors of financial capacity across the dementia spectrum: Normal aging, mild cognitive impairment, and Alzheimer's disease.

    PubMed

    Sherod, Megan G; Griffith, H Randall; Copeland, Jacquelynn; Belue, Katherine; Krzywanski, Sara; Zamrini, Edward Y; Harrell, Lindy E; Clark, David G; Brockington, John C; Powers, Richard E; Marson, Daniel C

    2009-03-01

    Financial capacity is a complex instrumental activity of daily living critical to independent functioning of older adults and sensitive to impairment in patients with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, little is known about the neurocognitive basis of financial impairment in dementia. We developed cognitive models of financial capacity in cognitively healthy older adults (n = 85) and patients with MCI (n = 113) and mild AD (n = 43). All participants were administered the Financial Capacity Instrument (FCI) and a neuropsychological test battery. Univariate correlation and multiple regression procedures were used to develop cognitive models of overall FCI performance across groups. The control model (R2 = .38) comprised (in order of entry) written arithmetic skills, delayed story recall, and simple visuomotor sequencing. The MCI model (R2 = .69) comprised written arithmetic skills, visuomotor sequencing and set alternation, and race. The AD model (R2 = .65) comprised written arithmetic skills, simple visuomotor sequencing, and immediate story recall. Written arithmetic skills (WRAT-3 Arithmetic) was the primary predictor across models, accounting for 27% (control model), 46% (AD model), and 55% (MCI model) of variance. Executive function and verbal memory were secondary model predictors. The results offer insight into the cognitive basis of financial capacity across the dementia spectrum of cognitive aging, MCI, and AD.

  5. PKCδ Inhibition Impairs Mammary Cancer Proliferative Capacity But Selects Cancer Stem Cells, Involving Autophagy.

    PubMed

    Berardi, Damián E; Flumian, Carolina; Rodriguez, Cristina E; Bessone, María I Díaz; Cirigliano, Stefano M; Joffé, Elisa D Bal de Kier; Fiszman, Gabriel L; Urtreger, Alejandro J; Todaro, Laura B

    2016-03-01

    Protein kinase C (PKC) is a family of serine/threonine kinases that regulate diverse cellular functions including cell death, proliferation, and survival. Recent studies have reported that PKCδ, are involved in apoptosis or autophagy induction. In the present study we focused on how PKCδ regulates proliferation and cancer stem cell (CSC) properties of the hormone-independent mammary cancer cell line LM38-LP, using pharmacological and genetic approaches. We found that pharmacological inhibition of PKCδ, by Rottlerin treatment, impairs in vitro LM38-LP proliferation through cell cycle arrest, inducing the formation of cytoplasmic-vacuoles. Using immunofluorescence we confirmed that Rottlerin treatment induced the apparition of LC3 dots in cell cytoplasm, and increased autophagy flux. On the other side, the same treatment increased CSC growth rate and self-renewal. Furthermore, Rottlerin pre-treatment induced in CSC the development of a "grape-like" morphology when they are growing in 3D cultures (Matrigel), usually associated with a malignant phenotype, as well as an increase in the number of experimental lung metastasis when these cells were inoculated in vivo. The PKCδ knockdown, by RNA interference, induced autophagy and increased CSC number, indicating that these effects are indeed exerted through a PKCδ dependent pathway. Finally, the increase in the number of mammospheres could be reversed by a 3MA treatment, suggesting that autophagy mechanism is necessary for the increased of CSC self-renewal induced by PKCδ inhibition. Here we demonstrated that PKCδ activity exerts a dual role through the autophagy mechanism, decreasing proliferative capacity of mammary tumor cells but also regulating tumor stem cell self-renewal. © 2015 Wiley Periodicals, Inc.

  6. Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women.

    PubMed

    Brownlie, Thomas; Utermohlen, Virginia; Hinton, Pamela S; Haas, Jere D

    2004-03-01

    We previously showed that iron supplementation significantly improves iron status and maximal work capacity in previously untrained, marginally iron-deficient women with a baseline serum transferrin receptor concentration > 8.0 mg/L. However, the effect of transferrin receptor status on adaptation in endurance capacity after aerobic training in these subjects has not been fully explored. Our objective was to examine the effect of baseline serum transferrin receptor status on adaptations in endurance capacity. Forty-one untrained, iron-depleted, nonanemic women were randomly assigned to receive either 100 mg FeSO(4) or a placebo for 6 wk in a double-blind trial. All subjects trained on cycle ergometers 5 d/wk for the last 4 wk of the study. Endurance capacity was assessed at baseline and after treatment by using a 15-km time trial conducted on a cycle ergometer. Significant treatment effects were observed for time to complete the 15-km time trial, work rate, and percentage of maximal oxygen uptake in subjects with a baseline serum transferrin receptor concentration > 8.0 mg/L. No significant treatment effects were observed in subjects with a normal baseline transferrin receptor concentration. Our findings suggest that, in the presence of overt tissue iron deficiency, iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women. This impairment can be corrected with iron supplementation.

  7. ABCA1-Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

    PubMed

    Yassine, Hussein N; Feng, Qingru; Chiang, Jiarong; Petrosspour, Larissa M; Fonteh, Alfred N; Chui, Helena C; Harrington, Michael G

    2016-02-12

    Animal and human studies indicate that ABCA1-mediated cholesterol transport is important in Alzheimer's disease (AD). We hypothesized that the efficiency of cerebrospinal fluid (CSF) to facilitate ABCA1-mediated cholesterol efflux would be reduced in participants with mild cognitive impairment (MCI) or AD compared with cognitively healthy participants. CSF was collected from a cross-sectional study of cognitively healthy participants (n=47) and participants with MCI (n=35) or probable AD (n=26).The capacity of CSF to mediate cholesterol transport was assessed using a BHK cell line that can be induced to express the ABCA1 transporter. ABCA1-mediated cholesterol efflux capacity was 30% less in participants with MCI or AD compared with cognitively healthy participants (P<0.001 for both). Cholesterol efflux capacity correlated with CSF cholesterol content (r=0.37, P<0.001). CSF phosphatidylcholine decreased in participants with MCI and AD compared with cognitively healthy participants (9% less in MCI and 27% less in AD compared with cognitively healthy participants, P=0.01) and correlated with CSF efflux capacity (r=0.3, P=0.001). CSF sphingomyelin also correlated with the efflux capacity (r=0.24, P=0.02). Concentrations of CSF apoA-I and apoE did not significantly correlate with measures of efflux capacity. In people with MCI and AD, the capacity of CSF to facilitate ABCA1-mediated cholesterol efflux is impaired. This lesser cholesterol efflux in MCI supports a pathophysiological role for ABCA1-mediated cholesterol transport in early neurodegeneration. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Investigating medical decision-making capacity in patients with cognitive impairment using a protocol based on linguistic features.

    PubMed

    Tallberg, Ing-Mari; Stormoen, Sara; Almkvist, Ove; Eriksdotter, Maria; Sundström, Erik

    2013-10-01

    A critical question is whether cognitively impaired patients have the competence for autonomous decisions regarding participation in clinical trials. The present study aimed to investigate medical decision-making capacity by use of a Swedish linguistic instrument for medical decision-making (LIMD) in hypothetical clinical trials in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Three comparable groups (age, education) participated in the study: AD (n = 20; MMSE: 24.1 ± 3.3) and MCI (n = 22; MMSE: 26.7 ± 2.4) patients and healthy controls (n = 37; MMSE: 29.1 ± 1.0). Medical decision-making capacity was operationalized as answers to questions regarding participation in three hypothetical clinical trials. Answers were scored regarding comprehension, evaluation and intelligibility of decisions, and a total LIMD score was used as the measure of medical decision-making ability. Groups differed significantly in LIMD with AD patients performing worst and MCI poorer than the control group. A strong association was found between all LIMD scores and diagnosis which supported the assertion that LIMD as it is designed is a one-dimensional instrument of medical decision-making capacity (MDMC). The results indicate that a fundamental communicative ability has an impact on the competence for autonomous decisions in cognitive impairment.

  9. Increased Muscle Sympathetic Nerve Activity and Impaired Executive Performance Capacity in Obstructive Sleep Apnea

    PubMed Central

    Goya, Thiago T.; Silva, Rosyvaldo F.; Guerra, Renan S.; Lima, Marta F.; Barbosa, Eline R.F.; Cunha, Paulo Jannuzzi; Lobo, Denise M.L.; Buchpiguel, Carlos A.; Busatto-Filho, Geraldo; Negrão, Carlos E.; Lorenzi-Filho, Geraldo; Ueno-Pardi, Linda M.

    2016-01-01

    impaired executive performance capacity in obstructive sleep apnea. SLEEP 2016;39(1):25–33. PMID:26237773

  10. Increased serum advanced glycation end products are associated with impairment in HDL antioxidative capacity in diabetic nephropathy.

    PubMed

    Zhou, Huali; Tan, Kathryn C B; Shiu, Sammy W M; Wong, Ying

    2008-03-01

    Advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications. Recent data suggest that AGEs may also interfere with the function of HDL and the reverse cholesterol transport pathway. We have investigated whether serum AGE level is associated with impairment in the antioxidative capacity of HDL and in the ability of serum to induce cholesterol efflux in type 2 diabetic patients with and without nephropathy. A total of 167 controls and 264 diabetic patients was recruited. The ability of serum to induce cellular cholesterol efflux and the capacity of HDL to inhibit LDL oxidation ex vivo was determined. Serum AGEs were assayed by competitive ELISA using a polyclonal rabbit antisera raised against AGE-RNase. Diabetic subjects were subdivided into three groups (normoalbuminuria, microalbuminuria and proteinuria). Serum AGEs were significantly increased in diabetic patients with microalbuminuria or proteinuria (P < 0.001). Cholesterol efflux was significantly decreased in all three groups of diabetic patients compared to controls (P < 0.001) whereas the antioxidative capacity of HDL was significantly impaired in patients with microalbuminuria or proteinuria (P < 0.01). No relationship between serum AGEs and cholesterol efflux was found. However, serum AGE concentration was significantly associated with the antioxidative capacity of HDL and this was partly due to the adverse effect of AGEs on paraoxonase-1 activity. In type 2 diabetic patients with incipient or overt nephropathy, increased serum concentration of AGEs was associated with impairment in the antioxidative capacity of HDL. Cholesterol efflux to serum was also reduced but was not related to serum AGEs.

  11. Sodium channel selectivity filter regulates antiarrhythmic drug binding.

    PubMed

    Sunami, A; Dudley, S C; Fozzard, H A

    1997-12-09

    Local anesthetic antiarrhythmic drugs block Na+ channels and have important clinical uses. However, the molecular mechanism by which these drugs block the channel has not been established. The family of drugs is characterized by having an ionizable amino group and a hydrophobic tail. We hypothesized that the charged amino group of the drug may interact with charged residues in the channel's selectivity filter. Mutation of the putative domain III selectivity filter residue of the adult rat skeletal muscle Na+ channel (micro1) K1237E increased resting lidocaine block, but no change was observed in block by neutral analogs of lidocaine. An intermediate effect on the lidocaine block resulted from K1237S and there was no effect from K1237R, implying an electrostatic effect of Lys. Mutation of the other selectivity residues, D400A (domain I), E755A (domain II), and A1529D (domain IV) allowed block by externally applied quaternary membrane-impermeant derivatives of lidocaine (QX314 and QX222) and accelerated recovery from block by internal QX314. Neo-saxitoxin and tetrodotoxin, which occlude the channel pore, reduced the amount of QX314 bound in D400A and A1529D, respectively. Block by outside QX314 in E755A was inhibited by mutation of residues in transmembrane segment S6 of domain IV that are thought to be part of an internal binding site. The results demonstrate that the Na+ channel selectivity filter is involved in interactions with the hydrophilic part of the drugs, and it normally limits extracellular access to and escape from their binding site just within the selectivity filter. Participation of the selectivity ring in antiarrhythmic drug binding and access locates this structure adjacent to the S6 segment.

  12. Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

    PubMed

    Ungvari, Zoltan; Tucsek, Zsuzsanna; Sosnowska, Danuta; Toth, Peter; Gautam, Tripti; Podlutsky, Andrej; Csiszar, Agnes; Losonczy, Gyorgy; Valcarcel-Ares, M Noa; Sonntag, William E; Csiszar, Anna

    2013-08-01

    Age-related impairment of angiogenesis is likely to play a central role in cerebromicrovascular rarefaction and development of vascular cognitive impairment, but the underlying mechanisms remain elusive. To test the hypothesis that dysregulation of Dicer1 (ribonuclease III, a key enzyme of the microRNA [miRNA] machinery) impairs endothelial angiogenic capacity in aging, primary cerebromicrovascular endothelial cells (CMVECs) were isolated from young (3 months old) and aged (24 months old) Fischer 344 × Brown Norway rats. We found an age-related downregulation of Dicer1 expression both in CMVECs and in small cerebral vessels isolated from aged rats. In aged CMVECs, Dicer1 expression was increased by treatment with polyethylene glycol-catalase. Compared with young cells, aged CMVECs exhibited altered miRNA expression profile, which was associated with impaired proliferation, adhesion to vitronectin, collagen and fibronectin, cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing technology), and impaired ability to form capillary-like structures. Overexpression of Dicer1 in aged CMVECs partially restored miRNA expression profile and significantly improved angiogenic processes. In young CMVECs, downregulation of Dicer1 (siRNA) resulted in altered miRNA expression profile associated with impaired proliferation, adhesion, migration, and tube formation, mimicking the aging phenotype. Collectively, we found that Dicer1 is essential for normal endothelial angiogenic processes, suggesting that age-related dysregulation of Dicer1-dependent miRNA expression may be a potential mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging.

  13. Urine Concentrating Capacity, Vasopressin and Copeptin in ADPKD and IgA Nephropathy Patients with Renal Impairment

    PubMed Central

    Bakker, Stephan J. L.; Boesten, Lianne S. M.; Duit, A. A. Margreeth; Franssen, Casper F. M.; Gaillard, Carlo A. J. M.; Gansevoort, Ron T.

    2017-01-01

    Background Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients have an impaired urine concentrating capacity. Increased circulating vasopressin (AVP) concentrations are supposed to play a role in the progression of ADPKD. We hypothesized that ADPKD patients have a more severely impaired urine concentrating capacity in comparison to other patients with chronic kidney disease at a similar level of kidney function, with consequently an enhanced AVP response to water deprivation with higher circulating AVP concentrations. Methods 15 ADPKD (eGFR<60) patients and 15 age-, sex- and eGFR-matched controls with IgA nephropathy (IgAN), underwent a water deprivation test to determine maximal urine concentrating capacity. Plasma and urine osmolality, urine aquaporin-2 (AQP2) and plasma AVP and copeptin (a surrogate marker for AVP) were measured at baseline and after water deprivation (average 16 hours). In ADPKD patients, height adjusted total kidney volume (hTKV) was measured by MRI. Results Maximal achieved urine concentration was lower in ADPKD compared to IgAN controls (533±138 vs. 642±148 mOsm/kg, p = 0.046), with particularly a lower maximal achieved urine urea concentration (223±74 vs. 299±72 mmol/L, p = 0.008). After water deprivation, plasma osmolality was similar in both groups although change in plasma osmolality was more profound in ADPKD due to a lower baseline plasma osmolality in comparison to IgAN controls. Copeptin and AVP increased significantly in a similar way in both groups. AVP, copeptin and urine AQP2 were inversely associated with maximal urine concentrating in both groups. Conclusions ADPKD patients have a more severely impaired maximal urine concentrating capacity with a lower maximal achieved urine urea concentration in comparison to IgAN controls with similar endogenous copeptin and AVP responses. PMID:28081165

  14. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts

    NASA Technical Reports Server (NTRS)

    Eckes, B.; Dogic, D.; Colucci-Guyon, E.; Wang, N.; Maniotis, A.; Ingber, D.; Merckling, A.; Langa, F.; Aumailley, M.; Delouvee, A.; Koteliansky, V.; Babinet, C.; Krieg, T.

    1998-01-01

    Loss of a vimentin network due to gene disruption created viable mice that did not differ overtly from wild-type littermates. Here, primary fibroblasts derived from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured, and biological functions were studied in in vitro systems resembling stress situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild-type cells. Vimentin-deficient cells also displayed reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli. Reorganization of collagen fibrils and contraction of collagen lattices were severely impaired. The spatial organization of focal contact proteins, as well as actin microfilament organization was disturbed. Thus, absence of a vimentin filament network does not impair basic cellular functions needed for growth in culture, but cells are mechanically less stable, and we propose that therefore they are impaired in all functions depending upon mechanical stability.

  15. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts

    NASA Technical Reports Server (NTRS)

    Eckes, B.; Dogic, D.; Colucci-Guyon, E.; Wang, N.; Maniotis, A.; Ingber, D.; Merckling, A.; Langa, F.; Aumailley, M.; Delouvee, A.; hide

    1998-01-01

    Loss of a vimentin network due to gene disruption created viable mice that did not differ overtly from wild-type littermates. Here, primary fibroblasts derived from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured, and biological functions were studied in in vitro systems resembling stress situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild-type cells. Vimentin-deficient cells also displayed reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli. Reorganization of collagen fibrils and contraction of collagen lattices were severely impaired. The spatial organization of focal contact proteins, as well as actin microfilament organization was disturbed. Thus, absence of a vimentin filament network does not impair basic cellular functions needed for growth in culture, but cells are mechanically less stable, and we propose that therefore they are impaired in all functions depending upon mechanical stability.

  16. Working Memory Capacity and Language Processes in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Marton, Klara; Schwartz, Richard G.

    2003-01-01

    This study examined the interaction between working memory and language comprehension in children with specific language impairment (SLI), focusing on the function of the central executive component and its interaction with the phonological loop (A. D. Baddeley, 1986) in complex working memory tasks. Thirteen children with SLI and 13 age-matched…

  17. Sustained Selective Attention Skills of Preschool Children with Specific Language Impairment: Evidence for Separate Attentional Capacities

    ERIC Educational Resources Information Center

    Spaulding, Tammie J.; Plante, Elena; Vance, Rebecca

    2008-01-01

    Purpose: The present study was designed to investigate the performance of preschool children with specific language impairment (SLI) and their typically developing (TD) peers on sustained selective attention tasks. Method: This study included 23 children diagnosed with SLI and 23 TD children matched for age, gender, and maternal education level.…

  18. Visual Impairment does not Limit Training Effects in Development of Aerobic and Anaerobic Capacity in Tandem Cyclists

    PubMed Central

    Malwina, Kamelska Anna; Krzysztof, Mazurek; Piotr, Zmijewski

    2015-01-01

    The study aimed to investigate the differences in the effects of 7-month training on aerobic and anaerobic capacity in tandem cycling athletes with and without visual impairment. In this study, Polish elite (n=13) and sub-elite (n=13) visually impaired (VI) (n=13; 40.8 ±12.8 years) and properly sighted (PS) (n=13; 36.7 ±12.2 years) tandem-cycling athletes participated voluntarily in 7-month routine training. The following pre-/post-training measurements were conducted on separate days: maximal oxygen uptake (VO2max) was estimated with age correction using the Physical Working Capacity test on a bicycle ergometer according to the Astrand-Ryhming method. Maximal power output (Pmax) was evaluated using the Quebec test on a bicycle ergometer. At baseline, VO2max (47.8 ±14.1 vs 42.0 ±8.3 ml/kg/min, respectively) and Pmax (11.5 ±1.5 vs 11.5 ±1.0 W/kg) did not differ significantly between PS and VI cyclists. However, differences in aerobic capacity were considered as clinically significant. Two-way ANOVA revealed that after 7 month training, there were statistically significant increases in VO2max (p=0.003) and Pmax (p=0.009) among VI (VO2max, +9.1%; Pmax, +6.3%) and PS (VO2max, +9.1%; Pmax, +11.7%) cyclists, however, no time × visual impairment interaction effect was found (VO2max, p=0.467; Pmax, p=0.364). After training, VO2max (p=0.03), but not Pmax (p=0.13), was significantly greater in elite compared to sub-elite tandem cyclists. VI and PS tandem cyclists showed similar rates of improvement in VO2max and Pmax after 7-month training. VO2max was a significant determinant of success in tandem cycling. This is one of the first studies providing reference values for aerobic and anaerobic capacity in visually impaired cyclists. PMID:26834877

  19. Visual Impairment does not Limit Training Effects in Development of Aerobic and Anaerobic Capacity in Tandem Cyclists.

    PubMed

    Malwina, Kamelska Anna; Krzysztof, Mazurek; Piotr, Zmijewski

    2015-11-22

    The study aimed to investigate the differences in the effects of 7-month training on aerobic and anaerobic capacity in tandem cycling athletes with and without visual impairment. In this study, Polish elite (n=13) and sub-elite (n=13) visually impaired (VI) (n=13; 40.8 ±12.8 years) and properly sighted (PS) (n=13; 36.7 ±12.2 years) tandem-cycling athletes participated voluntarily in 7-month routine training. The following pre-/post-training measurements were conducted on separate days: maximal oxygen uptake (VO2max) was estimated with age correction using the Physical Working Capacity test on a bicycle ergometer according to the Astrand-Ryhming method. Maximal power output (Pmax) was evaluated using the Quebec test on a bicycle ergometer. At baseline, VO2max (47.8 ±14.1 vs 42.0 ±8.3 ml/kg/min, respectively) and Pmax (11.5 ±1.5 vs 11.5 ±1.0 W/kg) did not differ significantly between PS and VI cyclists. However, differences in aerobic capacity were considered as clinically significant. Two-way ANOVA revealed that after 7 month training, there were statistically significant increases in VO2max (p=0.003) and Pmax (p=0.009) among VI (VO2max, +9.1%; Pmax, +6.3%) and PS (VO2max, +9.1%; Pmax, +11.7%) cyclists, however, no time × visual impairment interaction effect was found (VO2max, p=0.467; Pmax, p=0.364). After training, VO2max (p=0.03), but not Pmax (p=0.13), was significantly greater in elite compared to sub-elite tandem cyclists. VI and PS tandem cyclists showed similar rates of improvement in VO2max and Pmax after 7-month training. VO2max was a significant determinant of success in tandem cycling. This is one of the first studies providing reference values for aerobic and anaerobic capacity in visually impaired cyclists.

  20. Impaired exercise capacity after lung transplantation is related to delayed recovery of muscle strength.

    PubMed

    Walsh, James R; Chambers, Daniel C; Davis, Rebecca J; Morris, Norman R; Seale, Helen E; Yerkovich, Stephanie T; Hopkins, Peter M A

    2013-01-01

    Lung transplant recipients report reduced exercise capacity despite satisfactory graft function. We analysed changes in lung function, six-min walk distance (6MWD), and quadriceps strength in the first 26-wk post-transplant and examined what factors predict 6MWD recovery. All lung transplant recipients at a single institution between June 2007 and January 2011 were considered for inclusion. Lung function, 6MWD, and quadriceps strength corrected for body weight (QS%) were recorded pre- and two-, six-, 13-, and 26-wk post-transplant. Fifty recipients, of mean (± SD) age 42 (± 13) yr, were studied. Mean FEV1 % and 6MWD improved from 26.4% to 88.9% and from 397 to 549 m at 26 wk, respectively (both p < 0.001). QS% declined in the first two wk but had improved to above pre-transplant levels by 26 wk (p = 0.027). On multivariate analysis (n = 35), lower pre-transplant exercise capacity and greater recovery in muscle strength explained most of the improvement in exercise capacity. Delayed recovery of exercise capacity after lung transplantation is unrelated to delay in improvement in graft function, but occurs secondary to the slow recovery of muscle strength. Our findings show that additional controlled trials are needed to better understand the influence of exercise rehabilitation on improvement in exercise capacity post-transplantation.

  1. Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice.

    PubMed

    Yokota, Takashi; Kinugawa, Shintaro; Hirabayashi, Kagami; Matsushima, Shouji; Inoue, Naoki; Ohta, Yukihiro; Hamaguchi, Sanae; Sobirin, Mochamad A; Ono, Taisuke; Suga, Tadashi; Kuroda, Satoshi; Tanaka, Shinya; Terasaki, Fumio; Okita, Koichi; Tsutsui, Hiroyuki

    2009-09-01

    Insulin resistance or diabetes is associated with limited exercise capacity, which can be caused by the abnormal energy metabolism in skeletal muscle. Oxidative stress is involved in mitochondrial dysfunction in diabetes. We hypothesized that increased oxidative stress could cause mitochondrial dysfunction in skeletal muscle and make contribution to exercise intolerance in diabetes. C57/BL6J mice were fed on normal diet or high fat diet (HFD) for 8 wk to induce obesity with insulin resistance and diabetes. Treadmill tests with expired gas analysis were performed to determine the exercise capacity and whole body oxygen uptake (Vo(2)). The work (vertical distance x body weight) to exhaustion was reduced in the HFD mice by 36%, accompanied by a 16% decrease of peak Vo(2). Mitochondrial ADP-stimulated respiration, electron transport chain complex I and III activities, and mitochondrial content in skeletal muscle were decreased in the HFD mice. Furthermore, superoxide production and NAD(P)H oxidase activity in skeletal muscle were significantly increased in the HFD mice. Intriguingly, the treatment of HFD-fed mice with apocynin [10 mmol/l; an inhibitor of NAD(P)H oxidase activation] improved exercise intolerance and mitochondrial dysfunction in skeletal muscle without affecting glucose metabolism itself. The exercise capacity and mitochondrial function in skeletal muscle were impaired in type 2 diabetes, which might be due to enhanced oxidative stress. Therapies designed to regulate oxidative stress and maintain mitochondrial function could be beneficial to improve the exercise capacity in type 2 diabetes.

  2. Extending MIL-STD-1553 bandwidth: a study of impairments, EMI, and channel capacity

    NASA Astrophysics Data System (ADS)

    Hegarty, Michael G.

    2004-09-01

    This paper explores the possibility of increasing the data rates on existing MIL-STD-1553 networks beyond its current one megabit per second rate. A combination of empirical and theoretical methods is used in predicting the capacity of a MIL-STD-1553 network. The analysis begins with an assessment of the usable bandwidth in a 1553 network followed by the development of models to predict signal-to-noise ratios based on a transmit signal level that meets the emissions limits of MIL-STD-461 and a noise level that is representative of a real 1553 system. This paper presents the theoretical capacity limits for several 1553 network configurations. The results of the analysis predict that the theoretical capacity within a legacy MIL-STD-1553 system is expected to be several hundred megabits per second. The achievable rate depends on network configuration and usable bandwidth. Methods of approaching these theoretical capacity limits is not discussed in this paper, rather, this paper provides a framework and a baseline for the analysis of higher data rates over legacy MIL-STD-1553 networks.

  3. When Does Decisional Impairment Become Decisional Incompetence? Ethical and Methodological Issues in Capacity Research in Schizophrenia

    PubMed Central

    Kim, Scott Y H

    2006-01-01

    Most decision-making capacity (DMC) research has focused on measuring the decision-making abilities of patients, rather than on how such persons may be categorized as competent or incompetent. However, research ethics policies and practices either assume that we can differentiate or attempt to guide the differentiation of the competent from the incompetent. Thus there is a need to build on the recent advances in capacity research by conceptualizing and studying DMC as a categorical concept. This review discusses why there is a need for such research and addresses challenges and obstacles, both practical and theoretical. After a discussion of the potential obstacles and suggesting ways to overcome them, it discusses why clinicians with expertise in capacity assessments may be the best source of a provisional “gold standard” for criterion validation of categorical capacity status. The review provides discussions of selected key methodological issues in conducting research that treats DMC as a categorical concept, such as the issue of the optimal number of expert judges needed to generate a criterion standard and the kinds of information presented to the experts in obtaining their judgments. Future research needs are outlined. PMID:16177276

  4. More Is Generally Better: Higher Working Memory Capacity Does Not Impair Perceptual Category Learning

    ERIC Educational Resources Information Center

    Kalish, Michael L.; Newell, Ben R.; Dunn, John C.

    2017-01-01

    It is sometimes supposed that category learning involves competing explicit and procedural systems, with only the former reliant on working memory capacity (WMC). In 2 experiments participants were trained for 3 blocks on both filtering (often said to be learned explicitly) and condensation (often said to be learned procedurally) category…

  5. Impact of germline and somatic missense variations on drug binding sites.

    PubMed

    Yan, C; Pattabiraman, N; Goecks, J; Lam, P; Nayak, A; Pan, Y; Torcivia-Rodriguez, J; Voskanian, A; Wan, Q; Mazumder, R

    2017-03-01

    Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and

  6. Increased Left Ventricular Stiffness Impairs Exercise Capacity in Patients with Heart Failure Symptoms Despite Normal Left Ventricular Ejection Fraction

    PubMed Central

    Sinning, David; Kasner, Mario; Westermann, Dirk; Schulze, Karsten; Schultheiss, Heinz-Peter; Tschöpe, Carsten

    2011-01-01

    Aims. Several mechanisms can be involved in the development of exercise intolerance in patients with heart failure despite normal left ventricular ejection fraction (HFNEF) and may include impairment of left ventricular (LV) stiffness. We therefore investigated the influence of LV stiffness, determined by pressure-volume loop analysis obtained by conductance catheterization, on exercise capacity in HFNEF. Methods and Results. 27 HFNEF patients who showed LV diastolic dysfunction in pressure-volume (PV) loop analysis performed symptom-limited cardiopulmonary exercise testing (CPET) and were compared with 12 patients who did not show diastolic dysfunction in PV loop analysis. HFNEF patients revealed a lower peak performance (P = .046), breathing reserve (P = .006), and ventilation equivalent for carbon dioxide production at rest (P = .002). LV stiffness correlated with peak oxygen uptake (r = −0.636, P < .001), peak oxygen uptake at ventilatory threshold (r = −0.500, P = .009), and ventilation equivalent for carbon dioxide production at ventilatory threshold (r = 0.529, P = .005). Conclusions. CPET parameters such as peak oxygen uptake, peak oxygen uptake at ventilatory threshold, and ventilation equivalent for carbon dioxide production at ventilatory threshold correlate with LV stiffness. Increased LV stiffness impairs exercise capacity in HFNEF. PMID:21403885

  7. Gait analysis in chronic heart failure: The calf as a locus of impaired walking capacity.

    PubMed

    Panizzolo, Fausto A; Maiorana, Andrew J; Naylor, Louise H; Dembo, Lawrence; Lloyd, David G; Green, Daniel J; Rubenson, Jonas

    2014-11-28

    Reduced walking capacity, a hallmark of chronic heart failure (CHF), is strongly correlated with hospitalization and morbidity. The aim of this work was to perform a detailed biomechanical gait analysis to better identify mechanisms underlying reduced walking capacity in CHF. Inverse dynamic analyses were conducted in CHF patients and age- and exercise level-matched control subjects on an instrumented treadmill at self-selected treadmill walking speeds and at speeds representing +20% and -20% of the subjects' preferred speed. Surprisingly, no difference in preferred speed was observed between groups, possibly explained by an optimization of the mechanical cost of transport in both groups (the mechanical cost to travel a given distance; J/kg/m). The majority of limb kinematics and kinetics were also similar between groups, with the exception of greater ankle dorsiflexion angles during stance in CHF. Nevertheless, over two times greater ankle plantarflexion work during stance and per distance traveled is required for a given triceps surae muscle volume in CHF patients. This, together with a greater reliance on the ankle compared to the hip to power walking in CHF patients, especially at faster speeds, may contribute to the earlier onset of fatigue in CHF patients. This observation also helps explain the high correlation between triceps surae muscle volume and exercise capacity that has previously been reported in CHF. Considering the key role played by the plantarflexors in powering walking and their association with exercise capacity, our findings strongly suggest that exercise-based rehabilitation in CHF should not omit the ankle muscle group.

  8. ApoCIII enrichment in HDL impairs HDL-mediated cholesterol efflux capacity.

    PubMed

    Luo, Mengdie; Liu, Aiying; Wang, Shuai; Wang, Tianle; Hu, Die; Wu, Sha; Peng, Daoquan

    2017-05-24

    Apolipoprotein CIII (apoCIII) has been reported to be tightly associated with triglyceride metabolism and the susceptibility to coronary artery disease (CAD). Besides, apoCIII has also been found to affect the anti-apoptotic effects of HDL. However, the effect of apoCIII on HDL-mediated cholesterol efflux, the crucial function of HDL, has not been reported. A hospital-based case-control study was conducted to compare the apoCIII distribution in lipoproteins between CAD patients and nonCAD controls and to explore the relationship between HDL-associated apoCIII (apoCIIIHDL) and HDL-mediated cholesterol efflux. One hundred forty CAD patients and nighty nine nonCAD controls were included. Plasma apoCIII, apoCIIIHDL and cholesterol efflux capacity was measured. The apoCIIIHDL ratio (apoCIIIHDL over plasma apoCIII) was significantly higher in CAD patients than that in control group (0.52 ± 0.24 vs. 0.43 ± 0.22, P = 0.004). Both apoCIIIHDL and apoCIIIHDL ratio were inversely correlated with cholesterol efflux capacity (r = -0.241, P = 0.0002; r = -0.318, P < 0.0001, respectively). Stepwise multiple regression analysis revealed that the apoCIIIHDL ratio was an independent contributor to HDL-mediated cholesterol efflux capacity (standardized β = -0.325, P < 0.001). This study indicates that the presence of apoCIII in HDL may affect HDL-mediated cholesterol efflux capacity, implying the alternative role of apoCIII in the atherogenesis.

  9. Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

    PubMed

    Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

    2014-10-05

    We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus.

  10. Sentence Comprehension in Specific Language Impairment: A Task Designed to Distinguish between Cognitive Capacity and Syntactic Complexity

    PubMed Central

    Leonard, Laurence B.; Deevy, Patricia; Fey, Marc E.; Bredin-Oja, Shelley L.

    2013-01-01

    Purpose This study examined sentence comprehension in children with specific language impairment (SLI) in a manner designed to separate the contribution of cognitive capacity from the effects of syntactic structure. Method Nineteen children with SLI, 19 typically developing children matched for age (TD-A) and 19 younger typically developing children (TD-Y) matched according to sentence comprehension test scores responded to sentence comprehension items that varied in either length or their demands on cognitive capacity based on the nature of the foils competing with the target picture. Results The TD-A children were accurate across all item types. The SLI and TD-Y groups were less accurate than the TD-A group on items with greater length and, especially, on items with the greatest demands on cognitive capacity. The types of errors were consistent with failure to retain details of the sentence apart from syntactic structure. Conclusions The difficulty in the more demanding conditions seemed attributable to interference. Specifically, the children with SLI and the TD-Y children appeared to have difficulty retaining details of the target sentence when the information reflected in the foils closely resembled the information in the target sentence. PMID:22988286

  11. Shmt1 Heterozygosity Impairs Folate-Dependent Thymidylate Synthesis Capacity and Modifies Risk of Apcmin-Mediated Intestinal Cancer Risk

    PubMed Central

    MacFarlane, Amanda J.; Perry, Cheryll A.; McEntee, Michael F.; Lin, David M.; Stover, Patrick J.

    2010-01-01

    Folate-mediated one-carbon metabolism is required for the de novo synthesis of purines, thymidylate, and S-adenosylmethionine, the primary cellular methyl donor. Impairments in folate metabolism diminish cellular methylation potential and genome stability, which are risk factors for colorectal cancer (CRC). Cytoplasmic serine hydroxymethyltransferase (SHMT1) regulates the partitioning of folate-activated one-carbons between thymidylate and S-adenosylmethionine biosynthesis. Therefore, changes in SHMT1 expression enable the determination of the specific contributions made by thymidylate and S-adenosylmethionine biosynthesis to CRC risk. Shmt1 hemizygosity was associated with a decreased capacity for thymidylate synthesis, due to down regulation of enzymes in its biosynthetic pathway, namely thymidylate synthase and cytoplasmic thymidine kinase. Significant Shmt1-dependent changes to methylation capacity, gene expression and purine synthesis were not observed. Shmt1 hemizygosity was associated with increased risk for intestinal cancer in Apcmin/+ mice through a gene-by-diet interaction, indicating that the capacity for thymidylate synthesis modifies susceptibility to intestinal cancer in Apcmin/+ mice. PMID:21406397

  12. Decreased capacity for sodium export out of Arabidopsis chloroplasts impairs salt tolerance, photosynthesis and plant performance.

    PubMed

    Müller, Maria; Kunz, Hans-Henning; Schroeder, Julian I; Kemp, Grant; Young, Howard S; Neuhaus, H Ekkehard

    2014-05-01

    Salt stress is a widespread phenomenon, limiting plant performance in large areas around the world. Although various types of plant sodium/proton antiporters have been characterized, the physiological function of NHD1 from Arabidopsis thaliana has not been elucidated in detail so far. Here we report that the NHD1-GFP fusion protein localizes to the chloroplast envelope. Heterologous expression of AtNHD1 was sufficient to complement a salt-sensitive Escherichia coli mutant lacking its endogenous sodium/proton exchangers. Transport competence of NHD1 was confirmed using recombinant, highly purified carrier protein reconstituted into proteoliposomes, proving Na(+) /H(+) antiport. In planta NHD1 expression was found to be highest in mature and senescent leaves but was not induced by sodium chloride application. When compared to wild-type controls, nhd1 T-DNA insertion mutants showed decreased biomasses and lower chlorophyll levels after sodium feeding. Interestingly, if grown on sand and supplemented with high sodium chloride, nhd1 mutants exhibited leaf tissue Na(+) levels similar to those of wild-type plants, but the Na(+) content of chloroplasts increased significantly. These high sodium levels in mutant chloroplasts resulted in markedly impaired photosynthetic performance as revealed by a lower quantum yield of photosystem II and increased non-photochemical quenching. Moreover, high Na(+) levels might hamper activity of the plastidic bile acid/sodium symporter family protein 2 (BASS2). The resulting pyruvate deficiency might cause the observed decreased phenylalanine levels in the nhd1 mutants due to lack of precursors.

  13. Cold exposure impairs dark-pulse capacity to induce REM sleep in the albino rat.

    PubMed

    Baracchi, Francesca; Zamboni, Giovanni; Cerri, Matteo; Del Sindaco, Elide; Dentico, Daniela; Jones, Christine Ann; Luppi, Marco; Perez, Emanuele; Amici, Roberto

    2008-06-01

    In the albino rat, a REM sleep (REMS) onset can be induced with a high probability and a short latency when the light is suddenly turned off (dark pulse, DP) during non-REM sleep (NREMS). The aim of this study was to investigate to what extent DP delivery could overcome the integrative thermoregulatory mechanisms that depress REMS occurrence during exposure to low ambient temperature (Ta). To this aim, the efficiency of a non-rhythmical repetitive DP (3 min each) delivery during the first 6-h light period of a 12 h:12 h light-dark cycle in inducing REMS was studied in the rat, through the analysis of electroencephalogram, electrocardiogram, hypothalamic temperature and motor activity at different Tas. The results showed that DP delivery triggers a transition from NREMS to REMS comparable to that which occurs spontaneously. However, the efficiency of DP delivery in inducing REMS was reduced during cold exposure to an extent comparable with that observed in spontaneous REMS occurrence. Such impairment was associated with low Delta activity and high sympathetic tone when DPs were delivered. Repetitive DP administration increased REMS amount during the delivery period and a subsequent negative REMS rebound was observed. In conclusion, DP delivery did not overcome the integrative thermoregulatory mechanisms that depress REMS in the cold. These results underline the crucial physiological meaning of the mutual exclusion of thermoregulatory activation and REMS occurrence, and support the hypothesis that the suspension of the central control of body temperature is a prerequisite for REMS occurrence.

  14. Lack of the transcription factor C/EBPδ impairs the intrinsic capacity of peripheral neurons for regeneration.

    PubMed

    Lopez de Heredia, Luis; Magoulas, Charalambos

    2013-01-01

    Adult neurons of the peripheral nervous system (PNS), in contrast to those of the central nervous system, have a remarkable capacity to repair themselves after injury, yet the mechanisms underlying this regenerative propensity of peripheral neurons are far from completely understood. Here we show that the transcription factor CCAAT enhancer binding protein delta (C/EBPδ) is necessary for the efficient axonal regeneration of dorsal root ganglia (DRG) neurons after sciatic nerve crush injury. Loss of C/EBPδ substantially impairs axonal growth in dissociated cultured DRG neurons. In addition, lack of C/EPBδ causes a major reduction in the regenerative response of DRG neurons to a conditioning lesion, which is a well known paradigm of injury that enhances axonal growth due to a transcription-dependent cell body response. C/EBPδ is required for the induction of selected regeneration-associated genes. For example, the expression of SPRR1A (small proline-rich repeat protein 1A) is greatly reduced in DRG neurons of C/EBPδ knockout mice during axonal regeneration compared to those in wild-type mice, while the expression of GAP-43 (growth associated protein-43) and galanin is not affected. Nevertheless, the expected prompt recovery of sciatic nerve function after injury is severely impaired in C/EBPδ knockout mice, having a delay time of approximately 1 month for reaching the full function of recovering wild-type mice, suggesting that a transcription mechanism mediated by C/EBPδ is required for efficient axonal regeneration. Taken together, our results identify C/EBPδ as a crucial component of the transcriptional regulatory machinery which underlies the intrinsic capacity of peripheral neurons for axonal regeneration.

  15. Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity.

    PubMed

    Maamoun, Hatem; Zachariah, Matshediso; McVey, John H; Green, Fiona R; Agouni, Abdelali

    2017-03-01

    Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes. Hemeoxygenase-1 (HO-1) was shown to protect against oxidative stress in diabetes; however, its role in alleviating ER stress-induced endothelial dysfunction remains not fully elucidated. We aim here to test the protective role of HO-1 against high glucose-mediated ER stress and endothelial dysfunction and understand the underlying mechanisms with special emphasis on oxidative stress, inflammation and cell death. Human Umbilical Vein Endothelial Cells (HUVECs) were grown in either physiological or intermittent high concentrations of glucose for 5days in the presence or absence of Cobalt (III) Protoporphyrin IX chloride (CoPP, HO-1 inducer) or 4-Phenyl Butyric Acid (PBA, ER stress inhibitor). Using an integrated cellular and molecular approach, we then assessed ER stress and inflammatory responses, in addition to apoptosis and angiogenic capacity in these cells. Our results show that HO-1 induction prevented high glucose-mediated increase of mRNA and protein expression of key ER stress markers. Cells incubated with high glucose exhibited high levels of oxidative stress, activation of major inflammatory and apoptotic responses [nuclear factor (NF)-κB and c-Jun N-terminal kinase (JNK)] and increased rate of apoptosis; however, cells pre-treated with CoPP or PBA were fully protected. In addition, high glucose enhanced caspases 3 and 7 cleavage and activity and augmented cleaved poly ADP ribose polymerase (PARP) expression whereas HO-1 induction prevented these effects. Finally, HO-1 induction and ER stress inhibition prevented high glucose-induced reduction in NO release and impaired the angiogenic capacity of HUVECs, and enhanced vascular endothelial growth factor (VEGF)-A expression. Altogether, we show here the

  16. Integration of proprioceptive signals and attentional capacity during postural control are impaired but subject to improvement in dyslexic children.

    PubMed

    Quercia, Patrick; Demougeot, Laurent; Dos Santos, Mickaël; Bonnetblanc, François

    2011-04-01

    . Altogether, these results suggest that integration of proprioceptive signals in balance control and attentional capacity are impaired in dyslexic children. However, attention capacity during the control of stance could be improved significantly.

  17. Excess of dietary montmorillonite impairs growth performance, liver function, and antioxidant capacity in starter pigs.

    PubMed

    Zhao, H Y; Mao, X B; Yu, B; He, J; Zheng, P; Yu, J; Luo, J Q; Wang, Q Y; Chen, D W

    2017-07-01

    Montmorillonite (MMT) is widely used as a mycotoxin adsorbent in animal feeds, but its safety remains unclear. This study was conducted to investigate the safety of MMT supplementation in diets fed to starter pigs. A total of 120 32-d-old piglets (initial weight, 8.0 ± 0.9 kg) were randomly allotted into dietary treatments with graded MMT levels (0 [FS 0], 0.5% [FS 0.5], 1.0% [FS 1.0], 2.5% [FS 2.5], and 5.0% [FS 5.0]) with 6 replicate pens per treatment and 4 pigs per pen. All diets were fed for 28 d. As the MMT level increased, ADG and G:F changed in a linear and quadratic manner, while ADFI was linearly decreased ( > 0.05). Compared with FS 0, ADG, ADFI, and G:F of pigs in FS 1.0 increased ( < 0.05). However, the ADFI in pigs of FS 5.0 was lower than that in pigs of FS 0 ( < 0.05). The relative liver weight activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) changed in a linear and quadratic manner ( < 0.05). Compared with FS 0, pigs in FS 2.5 and FS 5.0 had a greater serum ALT ( < 0.05), while AST activity significantly increased in pigs of FS 5.0 ( < 0.05). Dietary MMT supplementation decreased serum Mg content in a linear and quadratic manner ( < 0.05), while Zn and Cu contents were linearly decreased ( < 0.05). Serum Zn and Cu contents of pigs in FS 0.5, FS 2.5, and FS 5.0 groups were lower than those in the control. Pigs fed with 2.5% and 5% MMT showed hepatic histopathological changes, including swelling, granular and vesicular degeneration, and apparent vacuolar degeneration. In addition, the content of serum total antioxidant capacity (T-AOC) and activity of glutathione peroxidase (GSH-PX) decreased in a linear and quadratic manner ( < 0.05). Compared to the control, 5.0% MMT significantly increased piglets' serum malondialdehyde (MDA) concentration and decreased GSH-PX activity ( < 0.05). T-AOC concentration in the pigs fed 2.5% and 5.0% MMT was lower than that in the control group ( < 0.05). Serum superoxide dismutase

  18. High-dose statin use does not impair aerobic capacity or skeletal muscle function in older adults

    PubMed Central

    Stock, Anthoney A.; Harman, S. Mitchell

    2008-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are lipid-lowering agents widely employed for atherosclerosis prevention. HMG-CoA reductase blockade reduces skeletal muscle coenzyme Q10 (CoQ10) levels and mitochondrial respiratory chain activities and may produce mild to severe skeletal muscle myopathy. This study investigated whether high-dose statin treatment would result in measurably decreased exercise capacity in older men and women. Maximal oxygen consumption, aerobic endurance, oxygen uptake kinetics, maximal strength, muscular power, and muscular endurance were measured before and after 12 weeks of statin treatment (simvastatin, 80 mg/day) in nine men and one woman, ages 55–76 years, with LDL-cholesterol levels >3.3 mmol/l (mean = 4.2 ± 0.2 mmol/l). Myalgia symptoms were assessed every 4 weeks. As expected, statin treatment resulted in significant decreases in LDL- and total-cholesterol levels (P < 0.01) with no significant changes in HDL-cholesterol or triglyceride levels. No significant changes were observed in aerobic capacity, endurance, oxygen kinetics or any measures of muscle function. No subject reported symptoms of myalgia, cramps, or weakness during the study. In the absence of myalgia or myopathic symptoms, high-dose simvastatin treatment did not impair exercise capacity in hyperlipidemic older individuals. We conclude that decreases in intramuscular CoQ10, in most patients on high dose statin treatment may not be clinically relevant, due to inter-individual variability in the degree of CoQ10 depletion, sensitivity of muscle to decreases in CoQ10, or both. PMID:19424852

  19. Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

    SciTech Connect

    Deshpande, Chandrika N.; Harrop, Stephen J.; Boucher, Yan; Hassan, Karl A.; Di Leo, Rosa; Xu, Xiaohui; Cui, Hong; Savchenko, Alexei; Chang, Changsoo; Labbate, Maurizio; Paulsen, Ian T.; Stokes, H.W.; Curmi, Paul M.G.; Mabbutt, Bridget C.

    2012-02-15

    The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. We report the 1.8 {angstrom} crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.

  20. POLG2 disease variants: analyses reveal a dominant negative heterodimer, altered mitochondrial localization and impaired respiratory capacity

    PubMed Central

    Young, Matthew J.; Humble, Margaret M.; DeBalsi, Karen L.; Sun, Kathie Y.; Copeland, William C.

    2015-01-01

    Human mitochondrial DNA (mtDNA) is replicated and repaired by the mtDNA polymerase gamma, polγ. Polγ is composed of three subunits encoded by two nuclear genes: (1) POLG codes for the 140-kilodalton (kDa) catalytic subunit, p140 and (2) POLG2 encodes the ∼110-kDa homodimeric accessory subunit, p55. Specific mutations are associated with POLG- or POLG2-related disorders. During DNA replication the p55 accessory subunit binds to p140 and increases processivity by preventing polγ's dissociation from the template. To date, studies have demonstrated that homodimeric p55 disease variants are deficient in the ability to stimulate p140; however, all patients currently identified with POLG2-related disorders are heterozygotes. In these patients, we expect p55 to occur as 25% wild-type (WT) homodimers, 25% variant homodimers and 50% heterodimers. We report the development of a tandem affinity strategy to isolate p55 heterodimers. The WT/G451E p55 heterodimer impairs polγ function in vitro, demonstrating that the POLG2 c.1352G>A/p.G451E mutation encodes a dominant negative protein. To analyze the subcellular consequence of disease mutations in HEK293 cells, we designed plasmids encoding p55 disease variants tagged with green fluorescent protein (GFP). P205R and L475DfsX2 p55 variants exhibit irregular diffuse mitochondrial fluorescence and unlike WT p55, they fail to form distinct puncta associated with mtDNA nucleoids. Furthermore, homogenous preparations of P205R and L475DfsX2 p55 form aberrant reducible multimers. We predict that abnormal protein folding or aggregation or both contribute to the pathophysiology of these disorders. Examination of mitochondrial bioenergetics in stable cell lines overexpressing GFP-tagged p55 variants revealed impaired mitochondrial reserve capacity. PMID:26123486

  1. Capacity of the Catalan and Spanish Versions of the Bilingual Aphasia Test to Distinguish between Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Gomez-Ruiz, Isabel; Aguilar-Alonso, Angel

    2011-01-01

    This study analysed the capacity of the Catalan and Spanish versions of the Bilingual Aphasia Test (BAT) to distinguish between normal and pathological aging. Both versions of the test were administered to 45 bilingual subjects: 15 healthy aging subjects, 15 patients with mild cognitive impairment and 15 patients with Alzheimer's disease. To…

  2. Capacity of the Catalan and Spanish Versions of the Bilingual Aphasia Test to Distinguish between Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Gomez-Ruiz, Isabel; Aguilar-Alonso, Angel

    2011-01-01

    This study analysed the capacity of the Catalan and Spanish versions of the Bilingual Aphasia Test (BAT) to distinguish between normal and pathological aging. Both versions of the test were administered to 45 bilingual subjects: 15 healthy aging subjects, 15 patients with mild cognitive impairment and 15 patients with Alzheimer's disease. To…

  3. Speech Perception and Phonological Short-Term Memory Capacity in Language Impairment: Preliminary Evidence from Adolescents with Specific Language Impairment (SLI) and Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Loucas, Tom; Riches, Nick Greatorex; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Baird, Gillian

    2010-01-01

    Background: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. Aims: This study aimed to investigate the…

  4. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    PubMed

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

  5. Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From Interstitial Fluid in Type 2 Diabetes Mellitus-Brief Report.

    PubMed

    Apro, Johanna; Tietge, Uwe J F; Dikkers, Arne; Parini, Paolo; Angelin, Bo; Rudling, Mats

    2016-05-01

    Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease, the mechanism of which is incompletely understood. Their high-density lipoprotein (HDL) particles in plasma have been reported to have impaired cholesterol efflux capacity. However, the efflux capacity of HDL from interstitial fluid (IF), the starting point for reverse cholesterol transport, has not been studied. We here investigated the cholesterol efflux capacity of HDL from IF and plasma from T2D patients and healthy controls. HDL was isolated from IF and peripheral plasma from 35 T2D patients and 35 age- and sex-matched healthy controls. Cholesterol efflux to HDL was determined in vitro, normalized for HDL cholesterol, using cholesterol-loaded macrophages. Efflux capacity of plasma HDL was 10% lower in T2D patients than in healthy controls, in line with previous observations. This difference was much more pronounced for HDL from IF, where efflux capacity was reduced by 28% in T2D. Somewhat surprisingly, the efflux capacity of HDL from IF was lower than that of plasma HDL, by 15% and 32% in controls and T2D patients, respectively. These data demonstrate that (1) HDL from IF has a lower cholesterol efflux capacity than plasma HDL and (2) the efflux capacity of HDL from IF is severely impaired in T2D when compared with controls. Because IF comprises the compartment where reverse cholesterol transport is initiated, the marked reduction in cholesterol efflux capacity of IF-HDL from T2D patients may play an important role for their increased risk to develop atherosclerosis. © 2016 The Authors.

  6. Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin.

    PubMed

    Awasthi, Saurabh; Murugan, N Arul; Saraswathi, N T

    2015-09-08

    The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs.

  7. Calorimetric investigation of diclofenac drug binding to a panel of moderately glycated serum albumins.

    PubMed

    Indurthi, Venkata S K; Leclerc, Estelle; Vetter, Stefan W

    2014-08-01

    Glycation alters the drug binding properties of serum proteins and could affect free drug concentrations in diabetic patients with elevated glycation levels. We investigated the effect of bovine serum albumin glycation by eight physiologically relevant glycation reagents (glucose, ribose, carboxymethyllysine, acetoin, methylglyoxal, glyceraldehyde, diacetyl and glycolaldehyde) on diclofenac drug binding. We used this non-steroidal anti-inflammatory drug diclofenac as a paradigm for acidic drugs with high serum binding and because of its potential cardiovascular risks in diabetic patients. Isothermal titration calorimetry showed that glycation reduced the binding affinity Ka of serum albumin and diclofenac 2 to 6-fold by reducing structural rigidity of albumin. Glycation affected the number of drug binding sites in a glycation reagent dependent manner and lead to a 25% decrease for most reagent, expect for ribose, with decreased by 60% and for the CML-modification, increased the number of binding sites by 60%. Using isothermal titration calorimetry and differential scanning calorimetry we derived the complete thermodynamic characterization of diclofenac binding to all glycated BSA samples. Our results suggest that glycation in diabetic patients could significantly alter the pharmacokinetics of the widely used over-the-counter NSDAI drug diclofenac and with possibly negative implications for patients.

  8. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding

    SciTech Connect

    Aller, Stephen G.; Yu, Jodie; Ward, Andrew; Weng, Yue; Chittaboina, Srinivas; Zhuo, Rupeng; Harrell, Patina M.; Trinh, Yenphuong T.; Zhang, Qinghai; Urbatsch, Ina L.; Chang, Geoffrey

    2009-04-22

    P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of -6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.

  9. Analysis of drug binding pockets and repurposing opportunities for twelve essential enzymes of ESKAPE pathogens

    PubMed Central

    Naz, Sadia; Ngo, Tony; Farooq, Umar

    2017-01-01

    Background The rapid increase in antibiotic resistance by various bacterial pathogens underlies the significance of developing new therapies and exploring different drug targets. A fraction of bacterial pathogens abbreviated as ESKAPE by the European Center for Disease Prevention and Control have been considered a major threat due to the rise in nosocomial infections. Here, we compared putative drug binding pockets of twelve essential and mostly conserved metabolic enzymes in numerous bacterial pathogens including those of the ESKAPE group and Mycobacterium tuberculosis. The comparative analysis will provide guidelines for the likelihood of transferability of the inhibitors from one species to another. Methods Nine bacterial species including six ESKAPE pathogens, Mycobacterium tuberculosis along with Mycobacterium smegmatis and Eschershia coli, two non-pathogenic bacteria, have been selected for drug binding pocket analysis of twelve essential enzymes. The amino acid sequences were obtained from Uniprot, aligned using ICM v3.8-4a and matched against the Pocketome encyclopedia. We used known co-crystal structures of selected target enzyme orthologs to evaluate the location of their active sites and binding pockets and to calculate a matrix of pairwise sequence identities across each target enzyme across the different species. This was used to generate sequence maps. Results High sequence identity of enzyme binding pockets, derived from experimentally determined co-crystallized structures, was observed among various species. Comparison at both full sequence level and for drug binding pockets of key metabolic enzymes showed that binding pockets are highly conserved (sequence similarity up to 100%) among various ESKAPE pathogens as well as Mycobacterium tuberculosis. Enzymes orthologs having conserved binding sites may have potential to interact with inhibitors in similar way and might be helpful for design of similar class of inhibitors for a particular species. The

  10. Ionizing Radiation Promotes the Acquisition of a Senescence-Associated Secretory Phenotype and Impairs Angiogenic Capacity in Cerebromicrovascular Endothelial Cells: Role of Increased DNA Damage and Decreased DNA Repair Capacity in Microvascular Radiosensitivity

    PubMed Central

    Ungvari, Zoltan; Podlutsky, Andrej; Sosnowska, Danuta

    2013-01-01

    Cerebromicrovascular rarefaction is believed to play a central role in cognitive impairment in patients receiving whole-brain irradiation therapy. To elucidate the mechanism underlying the deleterious effects of γ-irradiation on the cerebral microcirculation, rat primary cerebromicrovascular endothelial cells (CMVECs) were irradiated in vitro. We found that in CMVECs, γ-irradiation (2–8 Gy) elicited increased DNA damage, which was repaired less efficiently in CMVECs compared with neurons, microglia, and astrocytes. Increased genomic injury in CMVECs associated with increased apoptotic cell death. In the surviving cells, γ-irradiation promotes premature senescence (indicated by SA-β-galactosidase positivity and upregulation of p16INK4a), which was associated with impaired angiogenic capacity (decreased proliferation and tube-forming capacity). γ-Irradiated CMVECs acquired a senescence-associated secretory phenotype, characterized by upregulation of proinflammatory cytokines and chemokines (including IL-6, IL-1α, and MCP-1). Collectively, increased vulnerability of γ-irradiated CMVECs and their impaired angiogenic capacity likely contribute to cerebromicrovascular rarefaction and prevent regeneration of the microvasculature postirradiation. The acquisition of a senescence-associated secretory phenotype in irradiated CMVECs is biologically highly significant as changes in the cytokine microenvironment in the hippocampus may affect diverse biological processes relevant for normal neuronal function (including regulation of neurogenesis and the maintenance of the blood brain barrier). PMID:23689827

  11. Ionizing radiation promotes the acquisition of a senescence-associated secretory phenotype and impairs angiogenic capacity in cerebromicrovascular endothelial cells: role of increased DNA damage and decreased DNA repair capacity in microvascular radiosensitivity.

    PubMed

    Ungvari, Zoltan; Podlutsky, Andrej; Sosnowska, Danuta; Tucsek, Zsuzsanna; Toth, Peter; Deak, Ferenc; Gautam, Tripti; Csiszar, Anna; Sonntag, William E

    2013-12-01

    Cerebromicrovascular rarefaction is believed to play a central role in cognitive impairment in patients receiving whole-brain irradiation therapy. To elucidate the mechanism underlying the deleterious effects of γ-irradiation on the cerebral microcirculation, rat primary cerebromicrovascular endothelial cells (CMVECs) were irradiated in vitro. We found that in CMVECs, γ-irradiation (2-8 Gy) elicited increased DNA damage, which was repaired less efficiently in CMVECs compared with neurons, microglia, and astrocytes. Increased genomic injury in CMVECs associated with increased apoptotic cell death. In the surviving cells, γ-irradiation promotes premature senescence (indicated by SA-β-galactosidase positivity and upregulation of p16 (INK4a) ), which was associated with impaired angiogenic capacity (decreased proliferation and tube-forming capacity). γ-Irradiated CMVECs acquired a senescence-associated secretory phenotype, characterized by upregulation of proinflammatory cytokines and chemokines (including IL-6, IL-1α, and MCP-1). Collectively, increased vulnerability of γ-irradiated CMVECs and their impaired angiogenic capacity likely contribute to cerebromicrovascular rarefaction and prevent regeneration of the microvasculature postirradiation. The acquisition of a senescence-associated secretory phenotype in irradiated CMVECs is biologically highly significant as changes in the cytokine microenvironment in the hippocampus may affect diverse biological processes relevant for normal neuronal function (including regulation of neurogenesis and the maintenance of the blood brain barrier).

  12. Species-dependent stereoselective drug binding to albumin: a circular dichroism study.

    PubMed

    Pistolozzi, Marco; Bertucci, Carlo

    2008-03-01

    Drug binding to albumins from different mammalian species was investigated to disclose evidence of species-dependent stereoselectivity in drug-binding processes and affinities. This aspect is important for evaluating the reliability of extrapolating distribution data among species. The circular dichroism (CD) signal induced by drug binding to the albumins [human serum albumin (HSA), bovine serum albumin (BSA), rat serum albumin (RSA), and dog serum albumin (DSA)] were measured and analyzed. The binding of selected drugs and metabolites to HSA significantly differed from the binding to the other albumins in terms of affinity and conformation of the bound ligands. In particular, phenylbutazone, a marker of site one on HSA, showed a higher affinity for binding to BSA with respect to RSA, HSA, and DSA, respectively. In the case of diazepam, a marker of site two on HSA, the affinity decreased in order from HSA to DSA, RSA, and BSA. The induced CD spectra were similar in terms of energy and band signs, suggesting almost the same conformation for the bound drug to the different albumins. Stereoselectivity was high for the binding of ketoprofen to HSA and RSA. A different sign was observed for the CD spectra induced by the drug to the two albumins because of the prevalence of a different conformation of the bound drug. Interestingly, the same induced CD spectra were obtained using either the racemic form or the (S)-enantiomer. Finally, significant differences were observed in the affinity of bilirubin, being highest for BSA, then decreasing for RSA, HSA, and DSA. A more complex conformational equilibrium was observed for bound bilirubin.

  13. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line.

    PubMed

    Kienzler, Aude; Mahler, Barbara J; Van Metre, Peter C; Schweigert, Nathalie; Devaux, Alain; Bony, Sylvie

    2015-07-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line

    USGS Publications Warehouse

    Kienzler, Aude; Mahler, Barbara J.; Van Metre, Peter C.; Schweigert, Nathalie; Devaux, Alain; Bony, Sylvie

    2015-01-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity.

  15. Oligomycin frames a common drug-binding site in the ATP synthase

    SciTech Connect

    Symersky, Jindrich; Osowski, Daniel; Walters, D. Eric; Mueller, David M.

    2015-12-01

    We report the high-resolution (1.9 {angstrom}) crystal structure of oligomycin bound to the subunit c10 ring of the yeast mitochondrial ATP synthase. Oligomycin binds to the surface of the c10 ring making contact with two neighboring molecules at a position that explains the inhibitory effect on ATP synthesis. The carboxyl side chain of Glu59, which is essential for proton translocation, forms an H-bond with oligomycin via a bridging water molecule but is otherwise shielded from the aqueous environment. The remaining contacts between oligomycin and subunit c are primarily hydrophobic. The amino acid residues that form the oligomycin-binding site are 100% conserved between human and yeast but are widely different from those in bacterial homologs, thus explaining the differential sensitivity to oligomycin. Prior genetics studies suggest that the oligomycin-binding site overlaps with the binding site of other antibiotics, including those effective against Mycobacterium tuberculosis, and thereby frames a common 'drug-binding site.' We anticipate that this drug-binding site will serve as an effective target for new antibiotics developed by rational design.

  16. Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.

    PubMed

    Handing, Katarzyna B; Shabalin, Ivan G; Szlachta, Karol; Majorek, Karolina A; Minor, Wladek

    2016-03-01

    Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews.

  17. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

  18. High calcium enhances calcium oxalate crystal binding capacity of renal tubular cells via increased surface annexin A1 but impairs their proliferation and healing.

    PubMed

    Chutipongtanate, Somchai; Fong-ngern, Kedsarin; Peerapen, Paleerath; Thongboonkerd, Visith

    2012-07-06

    Hypercalciuria is associated with kidney stone formation and impaired renal function. However, responses of renal tubular cells upon exposure to high-calcium environment remain largely unknown. We thus performed a proteomic analysis of altered proteins in renal tubular cells induced by high-calcium and evaluated functional significance of these changes. MDCK cells were maintained with or without 20 mM CaCl(2) for 72 h. Cellular proteins were then analyzed by two-dimensional electrophoresis (2-DE) (n = 5 gels derived from 5 independent culture flasks per group). Spot matching and quantitative intensity analysis revealed 20 protein spots (from a total of 700) that were differentially expressed between the two groups. These altered proteins were then identified by Q-TOF-MS and MS/MS analyses, including those involved in calcium binding, protein synthesis, carbohydrate metabolism, lipid metabolism, cell proliferation, mitosis regulation, apoptosis, cell migration, oxidative stress, and ion transport. Protein network analysis and functional validation revealed that high-calcium-exposed cells had 36.5% increase in calcium oxalate monohydrate (COM) crystal-binding capacity. This functional change was consistent to the expression data in which annexin A1 (ANXA1), a membrane-associated calcium-binding protein, was markedly increased on the apical surface of high-calcium-exposed cells. Pretreatment with anti-ANXA1 antibody could neutralize this increasing crystal-binding capacity. Moreover, high-calcium exposure caused defects in cell proliferation and wound healing. These expression and functional data demonstrate the enhanced crystal-binding capacity but impaired cell proliferation and wound healing in renal tubular cells induced by high-calcium. Taken together, these phenomena may contribute, at least in part, to the pathogenic mechanisms of hypercalciuria-induced nephrolithiasis and impaired renal function. Our in vitro study offers several candidates for further

  19. Drug binding in human P-glycoprotein causes conformational changes in both nucleotide-binding domains.

    PubMed

    Loo, Tip W; Bartlett, M Claire; Clarke, David M

    2003-01-17

    The human multidrug resistance P-glycoprotein (P-gp, ABCB1) uses ATP to transport many structurally diverse compounds out of the cell. It is an ABC transporter with two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Recently, we showed that the "LSGGQ" motif in one NBD ((531)LSGGQ(535) in NBD1; (1176)LSGGQ(1180) in NBD2) is adjacent to the "Walker A" sequence ((1070)GSSGCGKS(1077) in NBD2; (427)GNSGCGKS(434) in NBD1) in the other NBD (Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2002) J. Biol. Chem. 277, 41303-41306). Drug substrates can stimulate or inhibit the ATPase activity of P-gp. Here, we report the effect of drug binding on cross-linking between the LSGGQ signature and Walker A sites (Cys(431)(NBD1)/C1176C(NBD2) and Cys(1074)(NBD2)/L531C(NBD1), respectively). Seven drug substrates (calcein-AM, demecolcine, cis(Z)-flupentixol, verapamil, cyclosporin A, Hoechst 33342, and trans(E)-flupentixol) were tested for their effect on oxidative cross-linking. Substrates that stimulated the ATPase activity of P-gp (calcein-AM, demecolcine, cis(Z)-flupentixol, and verapamil) increased the rate of cross-linking between Cys(431)(NBD1-Walker A)/C1176C(NBD2-LSGGQ) and between Cys(1074)(NBD2-Walker A)/L531C(NBD1-LSGGQ) when compared with cross-linking in the absence of drug substrate. By contrast, substrates that inhibited ATPase activity (cyclosporin A, Hoechst 33342, and trans(E)-flupentixol) decreased the rate of cross-linking. These results indicate that interaction between the LSGGQ motifs and Walker A sites must be essential for coupling drug binding to ATP hydrolysis. Drug binding in the transmembrane domains can induce long range conformational changes in the NBDs, such that compounds that stimulate or inhibit ATPase activity must decrease and increase, respectively, the distance between the Walker A and LSGGQ sequences.

  20. Impairment in emotion perception from body movements in individuals with bipolar I and bipolar II disorder is associated with functional capacity.

    PubMed

    Vaskinn, Anja; Lagerberg, Trine Vik; Bjella, Thomas D; Simonsen, Carmen; Andreassen, Ole A; Ueland, Torill; Sundet, Kjetil

    2017-12-01

    Individuals with bipolar disorder present with moderate impairments in social cognition during the euthymic state. The impairment extends to theory of mind and to the perception of emotion in faces and voices, but it is unclear if emotion perception from body movements is affected. The main aim of this study was to examine if participants with bipolar disorder perform worse than healthy control participants on a task using point-light displays of human full figures moving in a manner indicative of a basic emotion (angry, happy, sad, fearful, neutral/no emotion). A secondary research question was whether diagnostic subtypes (bipolar I, bipolar II) and history of psychosis impacted on this type of emotion perception. Finally, symptomatic, neurocognitive, and functional correlates of emotion perception from body movements were investigated. Fifty-three individuals with bipolar I (n = 29) or bipolar II (n = 24) disorder, and 84 healthy control participants were assessed for emotion perception from body movements. The bipolar group also underwent clinical, cognitive, and functional assessment. Research questions were analyzed using analyses of variance and bivariate correlations. The bipolar disorder group differed significantly from healthy control participants for emotion perception from body movements (Cohen's d = 0.40). Analyses of variance yielded no effects of sex, diagnostic subtype (bipolar I, bipolar II), or history of psychosis. There was an effect of emotion, indicating that some emotions are easier to recognize. The lack of a significant group × emotion interaction effect points, however, to this being so regardless of the presence of bipolar disorder. Performance was unrelated to manic and depressive symptom load but showed significant associations with neurocognition and functional capacity. Individuals with bipolar disorder had a small but significant impairment in the ability to perceive emotions from body movement. The impairment was global, i

  1. Whole body hyperthermia, but not skin hyperthermia, accelerates brain and locomotor limb circulatory strain and impairs exercise capacity in humans.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2017-01-01

    Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat-stressed humans, however, the contribution of elevations in skin (Tsk) versus whole body temperatures on exercise capacity has not been characterized. To ascertain their relationships with exercise capacity, blood temperature (TB), oxygen uptake (V̇O2), brain perfusion (MCA Vmean), locomotor limb hemodynamics, and hematological parameters were assessed during incremental cycling exercise with elevated skin (mild hyperthermia; HYPmild), combined core and skin temperatures (moderate hyperthermia; HYPmod), and under control conditions. Both hyperthermic conditions increased Tsk versus control (6.2 ± 0.2°C; P < 0.001), however, only HYPmod increased resting TB, leg blood flow and cardiac output (Q̇), but not MCA Vmean Throughout exercise, Tsk remained elevated in both hyperthermic conditions, whereas only TB was greater in HYPmod At exhaustion, oxygen uptake and exercise capacity were reduced in HYPmod in association with lower leg blood flow, MCA Vmean and mean arterial pressure (MAP), but similar maximal heart rate and TB The attenuated brain and leg perfusion with hyperthermia was associated with a plateau in MCA and two-legged vascular conductance (VC). Mechanistically, the falling MCA VC was coupled to reductions in PaCO2, whereas the plateau in leg vascular conductance was related to markedly elevated plasma [NA] and a plateau in plasma ATP These findings reveal that whole-body hyperthermia, but not skin hyperthermia, compromises exercise capacity in heat-stressed humans through the early attenuation of brain and active muscle blood flow.

  2. Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high-fat diet-induced diabetes.

    PubMed

    Takada, Shingo; Kinugawa, Shintaro; Matsushima, Shouji; Takemoto, Daisuke; Furihata, Takaaki; Mizushima, Wataru; Fukushima, Arata; Yokota, Takashi; Ono, Yoshiko; Shibata, Hiroshi; Okita, Koichi; Tsutsui, Hiroyuki

    2015-11-01

    What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus. We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin

  3. Working Memory Capacity as a Factor Influencing the Relationship between Language Outcome and Rehabilitation in Mandarin-Speaking Preschoolers with Congenital Hearing Impairment.

    PubMed

    Lo, Ming; Chen, Pei-Hua

    2017-01-01

    Memory processes could account for a significant part of the variance in language performances of hearing-impaired children. However, the circumstance in which the performance of hearing-impaired children can be nearly the same as the performance of hearing children remains relatively little studied. Thus, a group of pre-school children with congenital, bilateral hearing loss and a group of pre-school children with normal hearing were invited to participate in this study. In addition, the hearing-impaired participants were divided into two groups according to their working memory span. A language disorder assessment test for Mandarin-speaking preschoolers was used to measure the outcomes of receptive and expressive language of the two groups of children. The results showed that the high-span group performed as good as the hearing group, while the low-span group showed lower accuracy than the hearing group. A linear mixed-effects analysis showed that not only length of rehabilitation but also the memory span affected the measure of language outcome. Furthermore, the rehabilitation length positively correlated with the measure of expressive language only among the participants of the high-span group. The pattern of the results indicates that working memory capacity is one of the factors that could support the children to acquire age-equivalent language skills.

  4. Working Memory Capacity as a Factor Influencing the Relationship between Language Outcome and Rehabilitation in Mandarin-Speaking Preschoolers with Congenital Hearing Impairment

    PubMed Central

    Lo, Ming; Chen, Pei-Hua

    2017-01-01

    Memory processes could account for a significant part of the variance in language performances of hearing-impaired children. However, the circumstance in which the performance of hearing-impaired children can be nearly the same as the performance of hearing children remains relatively little studied. Thus, a group of pre-school children with congenital, bilateral hearing loss and a group of pre-school children with normal hearing were invited to participate in this study. In addition, the hearing-impaired participants were divided into two groups according to their working memory span. A language disorder assessment test for Mandarin-speaking preschoolers was used to measure the outcomes of receptive and expressive language of the two groups of children. The results showed that the high-span group performed as good as the hearing group, while the low-span group showed lower accuracy than the hearing group. A linear mixed-effects analysis showed that not only length of rehabilitation but also the memory span affected the measure of language outcome. Furthermore, the rehabilitation length positively correlated with the measure of expressive language only among the participants of the high-span group. The pattern of the results indicates that working memory capacity is one of the factors that could support the children to acquire age-equivalent language skills. PMID:28337168

  5. Microstructural Integrity of the Superior Cerebellar Peduncle Is Associated with an Impaired Proprioceptive Weighting Capacity in Individuals with Non-Specific Low Back Pain

    PubMed Central

    Pijnenburg, Madelon; Caeyenberghs, Karen; Janssens, Lotte; Goossens, Nina; Swinnen, Stephan P.; Sunaert, Stefan; Brumagne, Simon

    2014-01-01

    Introduction Postural control is a complex sensorimotor task that requires an intact network of white matter connections. The ability to weight proprioceptive signals is crucial for postural control. However, research into central processing of proprioceptive signals for postural control is lacking. This is specifically of interest in individuals with non-specific low back pain (NSLBP), because impairments in postural control have been observed as possible underlying mechanisms of NSLBP. Therefore, the objective was to investigate potential differences in sensorimotor white matter microstructure between individuals with NSLBP and healthy controls, and to determine whether the alterations in individuals with NSLBP are associated with the capacity to weight proprioceptive signals for postural control. Methods The contribution of proprioceptive signals from the ankle and back muscles to postural control was evaluated by local muscle vibration in 18 individuals with NSLBP and 18 healthy controls. Center of pressure displacement in response to muscle vibration was determined during upright standing on a stable and unstable support surface. Diffusion magnetic resonance imaging was applied to examine whether this proprioceptive contribution was associated with sensorimotor white matter microstructure. Results Individuals with NSLBP showed a trend towards a reduced fractional anisotropy along the left superior cerebellar peduncle compared to healthy controls (p = 0.039). The impaired microstructural integrity of the superior cerebellar peduncle in individuals with NSLBP was significantly correlated with the response to ankle muscle vibration (p<0.003). Conclusions In individuals with NSLBP, a decreased integrity of the superior cerebellar peduncle was associated with an increased reliance on ankle muscle proprioception, even on unstable support surface, which implies an impaired proprioceptive weighting capacity. Our findings emphasize the importance of the superior

  6. Muscle-specific adaptations, impaired oxidative capacity and maintenance of contractile function characterize diet-induced obese mouse skeletal muscle.

    PubMed

    Shortreed, Karin E; Krause, Matthew P; Huang, Julianna H; Dhanani, Dili; Moradi, Jasmin; Ceddia, Rolando B; Hawke, Thomas J

    2009-10-06

    The effects of diet-induced obesity on skeletal muscle function are largely unknown, particularly as it relates to changes in oxidative metabolism and morphology. Compared to control fed mice, mice fed a high fat diet (HFD; 60% kcal: fat) for 8 weeks displayed increased body mass and insulin resistance without overt fasting hyperglycemia (i.e. pre-diabetic). Histological analysis revealed a greater oxidative potential in the HFD gastrocnemius/plantaris (increased IIA, reduced IIB fiber-type percentages) and soleus (increased I, IIA cross-sectional areas) muscles, but no change in fiber type percentages in tibialis anterior muscles compared to controls. Intramyocellular lipid levels were significantly increased relative to control in HFD gastrocnemius/plantaris, but were similar to control values in the HFD soleus. Using a novel, single muscle fiber approach, impairments in complete palmitate and glucose oxidation (72.8+/-6.6% and 61.8+/-9.1% of control, respectively; p<0.05) with HFD were detected. These reductions were consistent with measures made using intact extensor digitorum longus and soleus muscles. Compared to controls, no difference in succinate dehydrogenase or citrate synthase enzyme activities were observed between groups in any muscle studied, however, short-chain fatty acyl CoA dehydrogenase (SCHAD) activity was elevated in the HFD soleus, but not tibialis anterior muscles. Despite these morphological and metabolic alterations, no significant difference in peak tetanic force or low-frequency fatigue rates were observed between groups. These findings indicate that HFD induces early adaptive responses that occur in a muscle-specific pattern, but are insufficient to prevent impairments in oxidative metabolism with continued high-fat feeding. Moreover, the morphological and metabolic changes which occur with 8 weeks of HFD do not significantly impact muscle contractile properties.

  7. Resistance exercise prevents impaired homocysteine metabolism and hepatic redox capacity in Walker-256 tumor-bearing male Wistar rats.

    PubMed

    Deminice, Rafael; Padilha, Camila de Souza; Borges, Fernando; da Silva, Lilian Eslaine Costa Mendes; Rosa, Flávia Troncon; Robinson, Jason Lorne; Cecchini, Rubens; Guarnier, Flávia Alessandra; Frajacomo, Fernando Trevisan

    2016-10-01

    The aim of this study was to investigate changes in homocysteine (Hcy) metabolism and redox balance in response to exercise treatment in a tumor-bearing rat model. Male Wistar rats were exposed, or not, to a resistance exercise program 6 wk before inoculation with Walker-256 tumor cells or vehicle. After application, rats maintained their routine for 12 d and were then sacrificed for plasma and liver analyses. Impaired Hcy metabolism was evident after 12 d of tumor cell inoculation as demonstrated by significantly increased (P < 0.05) plasma total homocysteine (tHcy) concentration (53%) and decreased plasma cysteine, methionine, and vitamin B12 concentrations. Decreased hepatic cystathionine β-synthase (CBS) and betaine-homocysteine S-methyltransferase mRNA levels were found in tumor-bearing rats but not in controls. Tumor inoculation also decreased levels of liver reduced glutathione (GSH) and increased hepatic oxidative stress compared with non-tumor controls. However, resistance exercise prevented the tumor-impaired transsulfuration pathway as demonstrated by the decreased plasma tHcy, hepatic CBS expression, and increased GSH in tumor-exercised versus tumor-sedentary rats. Remarkably, all measures of liver oxidative stress were suppressed by exercise training. Tumor weight was unchanged between groups. Resistance exercise prevented tHcy accumulation and liver oxidative damage caused by Walker-256 tumor cell inoculation; the modulatory effects of resistance exercise on Hcy metabolism appear to be at the level of transsulfuration pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. ABCG2 is a high-capacity urate transporter and its genetic impairment increases serum uric acid levels in humans.

    PubMed

    Nakayama, Akiyoshi; Matsuo, Hirotaka; Takada, Tappei; Ichida, Kimiyoshi; Nakamura, Takahiro; Ikebuchi, Yuki; Ito, Kousei; Hosoya, Tatsuo; Kanai, Yoshikatsu; Suzuki, Hiroshi; Shinomiya, Nariyoshi

    2011-12-01

    The ATP-binding cassette, subfamily G, member 2 (ABCG2/BCRP) gene encodes a well-known transporter, which exports various substrates including nucleotide analogs such as 3'-azido-3'-deoxythymidine (AZT). ABCG2 is also located in a gout-susceptibility locus (MIM 138900) on chromosome 4q, and has recently been identified by genome-wide association studies to relate to serum uric acid (SUA) and gout. Becuase urate is structurally similar to nucleotide analogs, we hypothesized that ABCG2 might be a urate exporter. To demonstrate our hypothesis, transport assays were performed with membrane vesicles prepared from ABCG2-overexpressing cells. Transport of estrone-3-sulfate (ES), a typical substrate of ABCG2, is inhibited by urate as well as AZT and ES. ATP-dependent transport of urate was then detected in ABCG2-expressing vesicles but not in control vesicles. Kinetic analysis revealed that ABCG2 is a high-capacity urate transporter that maintained its function even under high-urate concentration. The calculated parameters of ABCG2-mediated transport of urate were a Km of 8.24 ± 1.44 mM and a Vmax of 6.96 ± 0.89 nmol/min per mg of protein. Moreover, the quantitative trait locus (QTL) analysis performed in 739 Japanese individuals revealed that a dysfunctional variant of ABCG2 increased SUA as the number of minor alleles of the variant increased (p = 6.60 × 10(-5)). Because ABCG2 is expressed on the apical membrane in several tissues, including kidney, intestine, and liver, these findings indicate that ABCG2, a high-capacity urate exporter, has a physiological role of urate homeostasis in the human body through both renal and extrarenal urate excretion.

  9. Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser228 severely impairs antiatherogenic capacity.

    PubMed

    Dinnes, Donna Lee M; White, Melanie Y; Kockx, Maaike; Traini, Mathew; Hsieh, Victar; Kim, Mi-Jurng; Hou, Liming; Jessup, Wendy; Rye, Kerry-Anne; Thaysen-Andersen, Morten; Cordwell, Stuart J; Kritharides, Leonard

    2016-12-01

    Apolipoprotein A-I (apoA-I) is the major component of HDL and central to the ability of HDL to stimulate ATP-binding cassette transporter A1 (ABCA1)-dependent, antiatherogenic export of cholesterol from macrophage foam cells, a key player in the pathology of atherosclerosis. Cell-mediated modifications of apoA-I, such as chlorination, nitration, oxidation, and proteolysis, can impair its antiatherogenic function, although it is unknown whether macrophages themselves contribute to such modifications. To investigate this, human monocyte-derived macrophages (HMDMs) were incubated with human apoA-I under conditions used to induce cholesterol export. Two-dimensional gel electrophoresis and Western blot analysis identified that apoA-I is cleaved (∼20-80%) by HMDMs in a time-dependent manner, generating apoA-I of lower MW and isoelectric point. Mass spectrometry analysis identified a novel C-terminal cleavage site of apoA-I between Ser(228)-Phe(229) Recombinant apoA-I truncated at Ser(228) demonstrated profound loss of capacity to solubilize lipid and to promote ABCA1-dependent cholesterol efflux. Protease inhibitors, small interfering RNA knockdown in HMDMs, mass spectrometry analysis, and cathepsin B activity assays identified secreted cathepsin B as responsible for apoA-I cleavage at Ser(228) Importantly, C-terminal cleavage of apoA-I was also detected in human carotid plaque. Cleavage at Ser(228) is a novel, functionally important post-translational modification of apoA-I mediated by HMDMs that limits the antiatherogenic properties of apoA-I.-Dinnes, D. L. M., White, M. Y., Kockx, M., Traini, M., Hsieh, V., Kim, M.-J., Hou, L., Jessup, W., Rye, K.-A., Thaysen-Andersen, M., Cordwell, S. J., Kritharides, L. Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser(228) severely impairs antiatherogenic capacity. © FASEB.

  10. Anguillicola crassus impairs the silvering-related enhancements of the ROS defense capacity in swimbladder tissue of the European eel (Anguilla anguilla).

    PubMed

    Schneebauer, Gabriel; Hanel, Reinhold; Pelster, Bernd

    2016-10-01

    In a process called silvering, European eels prepare for their long-distance migration from European freshwater systems to the Sargasso Sea for reproduction. During this journey, eels perform extended diel vertical migrations, and the concomitant changes in hydrostatic pressure significantly affect the swimbladder, functioning as a buoyancy organ. As the swimbladder is primarily filled with oxygen, the tissue has to cope with extreme hyperoxic conditions, which typically are accompanied by the generation of reactive oxygen species (ROS) and oxidative stress. In addition, since the introduction of the parasitic nematode Anguillicola crassus in the early 1980s, swimbladder function of most of the European eels is impaired by the infection with this parasite. However, the exact pathways to detoxify ROS and how these pathways are affected by silvering or the infection are still unknown. In swimbladder and muscle tissue from uninfected and infected yellow, and from uninfected and infected silver eels, we measured the level of lipid peroxidation, which increases with ROS stress. To assess the capacity of the ROS defense systems, we analyzed the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), and determined the concentration of the antioxidant glutathione (GSH + GSSG). In swimbladder tissue, we found increased concentrations of GSH + GSSG as well as higher activities of SOD, GPx and GR, suggesting that SOD and the glutathione cycle are important for ROS detoxification. Comparing swimbladder tissue of uninfected yellow with uninfected silver eels, the concentration of GSH + GSSG and the activity of SOD were higher after silvering, corresponding with lower levels of lipid peroxidation. Whereas in yellow eels the infection with A. crassus had no effect, in silver eels the capacity to cope with ROS was significantly impaired. In muscle tissue, silvering or the infection only affected the activity of SOD

  11. Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects

    PubMed Central

    Smith, Kyle P.; Gifford, Kathleen M.; Waitzman, Joshua S.; Rice, Sarah E.

    2014-01-01

    While it is currently estimated that 40–50% of eukaryotic proteins are phosphorylated, little is known about the frequency and local effects of phosphorylation near pharmaceutical inhibitor binding sites. In this study, we investigated how frequently phosphorylation may affect the binding of drug inhibitors to target proteins. We examined the 453 non-redundant structures of soluble mammalian drug target proteins bound to inhibitors currently available in the Protein Data Bank (PDB). We cross-referenced these structures with phosphorylation data available from the PhosphoSitePlus database. 322/453 (71%) of drug targets have evidence of phosphorylation that has been validated by multiple methods or labs. For 132/453 (29%) of those, the phosphorylation site is within 12Å of the small molecule-binding site, where it would likely alter small molecule binding affinity. We propose a framework for distinguishing between drug-phosphorylation site interactions that are likely to alter the efficacy of drugs vs. those that are not. In addition we highlight examples of well-established drug targets, such as estrogen receptor alpha, for which phosphorylation may affect drug affinity and clinical efficacy. Our data suggest that phosphorylation may affect drug binding and efficacy for a significant fraction of drug target proteins. PMID:24833420

  12. Effect of bioceramic functional groups on drug binding and release kinetics

    NASA Astrophysics Data System (ADS)

    Trujillo, Christopher

    Bioceramics have been studied extensively as drug delivery systems (DDS). Those studies have aimed to tailor the drug binding and release kinetics to successfully treat infections and other diseases. This research suggests that the drug binding and release kinetics are predominantly driven by the functional groups available on the surface of a bioceramic. The goal of the present study is to explain the role of silicate and phosphate functional groups in drug binding to and release kinetics from bioceramics. alpha-cristobalite (Cris; SiO2) particles (90-150 microm) were prepared and doped with 0 microg (P-0), 39.1 microg (P-39.1), 78.2 microg (P-78.2), 165.5 microg (P-165.5) or 331 microg (P-331) of P 2O5 per gram Cris, using 85% orthophosphoric (H3PO 4) acid and thermal treatment. The material structure was analyzed using X-ray diffraction (XRD) with Rietveld Refinement and Fourier Transform Infrared (FTIR) spectroscopy with Gaussian fitting. XRD demonstrated an increase from sample P-0 (170.5373 A3) to P-331 (170.6466 A 3) in the unit cell volume as the P2O5 concentration increased in the material confirming phosphate silicate substitution in Cris. Moreover, FTIR showed the characteristic bands of phosphate functional groups of nu4 PO4/O-P-O bending, P-O-P stretching, P-O-P bending, P=O stretching, and P-O-H bending in doped Cris indicating phosphate incorporation in the silicate structure. Furthermore, FTIR showed that the nu4 PO4/O-P-O bending band around 557.6 cm-1 and P=O stretching band around 1343.9 cm-1 increased in area for samples P-39.1 to P-331 from 3.5 to 10.5 and from 10.1 to 22.4, respectively due to phosphate doping. In conjunction with the increase of the nu4 PO4/O-P-O bending band and P=O stretching band, a decrease in area of the O-Si-O bending bands around 488.1 and 629.8 cm-1 was noticed for samples P-39.1 to P-331 from 5 to 2 and from 11.8 to 5.4, respectively. Furthermore, Cris samples (200 mg, n=5 for each sample) were immersed separately in

  13. Low pH conditions impair module capacity to regenerate in a calcified colonial invertebrate, the bryozoan Cryptosula pallasiana.

    PubMed

    Lombardi, Chiara; Taylor, Paul D; Cocito, Silvia; Bertolini, Camilla; Calosi, Piero

    2017-04-01

    Many aquatic animals grow into colonies of repeated, genetically identical, modules (zooids). Zooid interconnections enable colonies to behave as integrated functional units, while plastic responses to environmental changes may affect individual zooids. Plasticity includes the variable partitioning of resources to sexual reproduction, colony growth and maintenance. Maintenance often involves regeneration, which is also a routine part of the life history in some organisms, such as bryozoans. Here we investigate changes in regenerative capacity in the encrusting bryozoan Cryptosula pallasiana when cultured at different seawater pCO2 levels. The proportion of active zooids showing polypide regeneration was highest at current oceanic pH (8.1), but decreased progressively as pH declined below that value, reaching a six-fold reduction at pH 7.0. The zone of budding of new zooids at the colony periphery declined in size below pH 7.7. Under elevated pCO2 conditions, already experienced sporadically in coastal areas, skeletal corrosion was accompanied by the proportional reallocation of resources from polypide regeneration in old zooids to the budding of new zooids at the edge of the colony. Thus, future ocean acidification can affect colonial organisms by changing how they allocate resources, with potentially profound impacts on life-history patterns and ecological interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Impaired regenerative capacity and lower revertant fibre expansion in dystrophin-deficient mdx muscles on DBA/2 background

    PubMed Central

    Rodrigues, Merryl; Echigoya, Yusuke; Maruyama, Rika; Lim, Kenji Rowel Q.; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy, one of the most common lethal genetic disorders, is caused by mutations in the DMD gene and a lack of dystrophin protein. In most DMD patients and animal models, sporadic dystrophin-positive muscle fibres, called revertant fibres (RFs), are observed in otherwise dystrophin-negative backgrounds. RFs are thought to arise from skeletal muscle precursor cells and clonally expand with age due to the frequent regeneration of necrotic fibres. Here we examined the effects of genetic background on muscle regeneration and RF expansion by comparing dystrophin-deficient mdx mice on the C57BL/6 background (mdx-B6) with those on the DBA/2 background (mdx-DBA), which have a more severe phenotype. Interestingly, mdx-DBA muscles had significantly lower RF expansion than mdx-B6 in all age groups, including 2, 6, 12, and 18 months. The percentage of centrally nucleated fibres was also significantly lower in mdx-DBA mice compared to mdx-B6, indicating that less muscle regeneration occurs in mdx-DBA. Our study aligns with the model that RF expansion reflects the activity of precursor cells in skeletal muscles, and it serves as an index of muscle regeneration capacity. PMID:27924830

  15. Eccentric Contraction-Induced Muscle Injury: Reproducible, Quantitative, Physiological Models to Impair Skeletal Muscle's Capacity to Generate Force.

    PubMed

    Call, Jarrod A; Lowe, Dawn A

    2016-01-01

    In order to investigate the molecular and cellular mechanisms of muscle regeneration an experimental injury model is required. Advantages of eccentric contraction-induced injury are that it is a controllable, reproducible, and physiologically relevant model to cause muscle injury, with injury being defined as a loss of force generating capacity. While eccentric contractions can be incorporated into conscious animal study designs such as downhill treadmill running, electrophysiological approaches to elicit eccentric contractions and examine muscle contractility, for example before and after the injurious eccentric contractions, allows researchers to circumvent common issues in determining muscle function in a conscious animal (e.g., unwillingness to participate). Herein, we describe in vitro and in vivo methods that are reliable, repeatable, and truly maximal because the muscle contractions are evoked in a controlled, quantifiable manner independent of subject motivation. Both methods can be used to initiate eccentric contraction-induced injury and are suitable for monitoring functional muscle regeneration hours to days to weeks post-injury.

  16. Exercise-induced torsional dyssynchrony relates to impaired functional capacity in patients with heart failure and normal ejection fraction.

    PubMed

    Tan, Yu Ting; Wenzelburger, Frauke Wg; Sanderson, John E; Leyva, Francisco

    2013-02-01

    Left ventricular (LV) systole and diastole are intimately dependent on myocardial torsion, which involves coupling between myocardial rotation (twisting in systole and untwisting in diastole) and longitudinal motion. Heart failure with normal ejection fraction (HFNEF) is known to involve exercise-induced wall motion abnormalities, but torsion on exercise has not been explored. We hypothesised that torsional dyssynchrony may also be involved and be exaggerated by exercise. 67 patients (age 73±7 years, 45 female) with HFNEF and 38 controls underwent cardiopulmonary exercise testing and echocardiography at rest and on supine exercise. Analysis of three plane motions was performed using speckle tracking and tissue Doppler imaging. Torsional dyssynchrony was quantified as the SD of the time to peak systolic motion (SDSM) (basal and apical rotation, longitudinal and radial displacement); the time difference between peak twist and peak longitudinal displacement (twist-longitudinal motion delay, TLMD) and the ratio of untwist to longitudinal extension (UT:LE). At rest, HFNEF patients had similar SDSM, TLMD and UT:LE compared with controls. Exercise was associated with significantly more dyssynchrony in the HFNEF patients (SDSM 38.8±27.6 ms vs 25.9±15.5 ms, p=0.02; TLMD 28.4±46.2 ms vs 2.9±31.2 ms, p=0.005 and UT:LE 10.4±15.3 vs 3.3±3.8, p=0.022). The SDSM correlated positively with LV wall thickness (r=0.31, p=0.015) and negatively with peak oxygen consumption (r=-0.299, p=0.01) and changes in stroke volume on exercise (r=-0.371, p=0.001). HFNEF involves exercise-induced torsional dyssynchrony in systole and diastole, which relates to LV hypertrophy as well as exercise capacity.

  17. Catalytic Transitions in the Human MDR1 P-Glycoprotein Drug Binding Sites

    PubMed Central

    2012-01-01

    Multidrug resistance proteins that belong to the ATP-binding cassette family like the human P-glycoprotein (ABCB1 or Pgp) are responsible for many failed cancer and antiviral chemotherapies because these membrane transporters remove the chemotherapeutics from the targeted cells. Understanding the details of the catalytic mechanism of Pgp is therefore critical to the development of inhibitors that might overcome these resistances. In this work, targeted molecular dynamics techniques were used to elucidate catalytically relevant structures of Pgp. Crystal structures of homologues in four different conformations were used as intermediate targets in the dynamics simulations. Transitions from conformations that were wide open to the cytoplasm to transition state conformations that were wide open to the extracellular space were studied. Twenty-six nonredundant transitional protein structures were identified from these targeted molecular dynamics simulations using evolutionary structure analyses. Coupled movement of nucleotide binding domains (NBDs) and transmembrane domains (TMDs) that form the drug binding cavities were observed. Pronounced twisting of the NBDs as they approached each other as well as the quantification of a dramatic opening of the TMDs to the extracellular space as the ATP hydrolysis transition state was reached were observed. Docking interactions of 21 known transport ligands or inhibitors were analyzed with each of the 26 transitional structures. Many of the docking results obtained here were validated by previously published biochemical determinations. As the ATP hydrolysis transition state was approached, drug docking in the extracellular half of the transmembrane domains seemed to be destabilized as transport ligand exit gates opened to the extracellular space. PMID:22647192

  18. Drug binding and mobility relating to the thermal fluctuation in fluid lipid membranes

    NASA Astrophysics Data System (ADS)

    Okamura, Emiko; Yoshii, Noriyuki

    2008-12-01

    Drug binding and mobility in fluid lipid bilayer membranes are quantified in situ by using the multinuclear solution NMR combined with the pulsed-field-gradient technique. One-dimensional and pulsed-field-gradient F19 and H1 NMR signals of an anticancer drug, 5-fluorouracil (5FU) are analyzed at 283-313 K in the presence of large unilamellar vesicles (LUVs) of egg phosphatidylcholine (EPC) as model cell membranes. The simultaneous observation of the membrane-bound and free 5FU signals enables to quantify in what amount of 5FU is bound to the membrane and how fast 5FU is moving within the membrane in relation to the thermal fluctuation of the soft, fluid environment. It is shown that the mobility of membrane-bound 5FU is slowed down by almost two orders of magnitude and similar to the lipid movement in the membrane, the movement closely related to the intramembrane fluidity. The mobility of 5FU and EPC is, however, not similar at 313 K; the 5FU movement is enhanced in the membrane as a result of the loose binding of 5FU in the lipid matrices. The membrane-bound fraction of 5FU is ˜0.1 and almost unaltered over the temperature range examined. It is also independent of the 5FU concentration from 2 to 30 mM with respect to the 40-50 mM LUV. The free energy of the 5FU binding is estimated at -4 to -2 kJ/mol, the magnitude always close to the thermal fluctuation, 2.4-2.6 kJ/mol.

  19. Drug design for protein kinases and phosphatases: flexible-receptor docking, binding affinity and specificity, and drug-binding kinetics.

    PubMed

    Wong, Chung F; Bairy, Sneha

    2013-01-01

    This article reviews some of our experiences on applying computational techniques to aid the design of drugs targeting protein kinases and phosphatases. It is not a comprehensive review. Rather, it focuses on several less explored approaches or ideas that we have experiences on. It reviews some recent improvements on the Poisson-Boltzmann/Surface Area model for calculating binding affinity and discusses ways to perform calculations that are more tolerant to statistical and systematic errors. Several new ways to incorporate protein flexibility in molecular docking and estimating binding affinity are also discussed. Its discussions also go beyond binding affinity to considering drug-binding kinetics, not only on investigating protein-ligand interactions in isolation, but also on accounting for upstream and downstream influences that can occur in cells, through kinetic modeling of cell signaling. This review also describes a quick molecular simulation method for understanding drug-binding kinetics at the molecular level, with the hope of generating guiding principles for designing drugs with the desired kinetic properties. Sources of drug-binding selectivity that appear obvious but often overlooked are also discussed.

  20. Impaired left ventricular myocardial mechanics and their relation to pulmonary regurgitation, right ventricular enlargement and exercise capacity in asymptomatic children after repair of tetralogy of Fallot.

    PubMed

    Fernandes, Fernanda P; Manlhiot, Cedric; Roche, Susan L; Grosse-Wortmann, Lars; Slorach, Cameron; McCrindle, Brian W; Mertens, Luc; Kantor, Paul F; Friedberg, Mark K

    2012-05-01

    Left ventricular (LV) dysfunction is common in adults late after repair of tetralogy of Fallot (TOF). The early detection of myocardial dysfunction may be important, but LV myocardial strain and dyssynchrony are not well studied in children with TOF. The objective of this study was to investigate LV strain and dyssynchrony in asymptomatic children and adolescents after contemporary repair of TOF. The hypothesis was that impaired LV myocardial mechanics are related to pulmonary regurgitation, right ventricular (RV) enlargement, and exercise capacity. Children and adolescents were prospectively studied after TOF repair. LV regional strain and dyssynchrony were assessed using two-dimensional speckle-tracking echocardiography. Ventricular volumes, ejection fraction, and pulmonary regurgitation were assessed using magnetic resonance imaging. Exercise capacity was determined using metabolic exercise testing. One hundred twenty-four subjects (53 patients with TOF and 71 controls) were studied. Regional circumferential (e.g., basal lateral wall, -15.0 ± 7.0% vs -19.0 ± 7.0%, P = .02) and radial (e.g., basal posterior wall, 32.0 ± 18.0% vs 48.0 ± 21.0%, P < .001) LV strain and longitudinal septal strain (-18.5 ± 3.5% vs -20.2 ± 2.8%, P = .01) were significantly reduced in patients with TOF compared with controls. LV mechanical dyssynchrony indices were not significantly different between groups (e.g., standard deviation of time to peak circumferential strain, 52.5 ± 40.4 vs 50.5 ± 27.1 msec, P = .81). Higher pulmonary regurgitation volume and larger RV end-diastolic volume were associated with decreased LV radial strain (P = .09). There was no association between LV longitudinal, radial, or circumferential dyssynchrony and indexed pulmonary regurgitation flow volume, RV end-diastolic volume, or RV ejection fraction. LV circumferential and radial strain are significantly reduced in children and adolescents after TOF repair and are associated with pulmonary

  1. Gated auditory speech perception in elderly hearing aid users and elderly normal-hearing individuals: effects of hearing impairment and cognitive capacity.

    PubMed

    Moradi, Shahram; Lidestam, Björn; Hällgren, Mathias; Rönnberg, Jerker

    2014-07-31

    This study compared elderly hearing aid (EHA) users and elderly normal-hearing (ENH) individuals on identification of auditory speech stimuli (consonants, words, and final word in sentences) that were different when considering their linguistic properties. We measured the accuracy with which the target speech stimuli were identified, as well as the isolation points (IPs: the shortest duration, from onset, required to correctly identify the speech target). The relationships between working memory capacity, the IPs, and speech accuracy were also measured. Twenty-four EHA users (with mild to moderate hearing impairment) and 24 ENH individuals participated in the present study. Despite the use of their regular hearing aids, the EHA users had delayed IPs and were less accurate in identifying consonants and words compared with the ENH individuals. The EHA users also had delayed IPs for final word identification in sentences with lower predictability; however, no significant between-group difference in accuracy was observed. Finally, there were no significant between-group differences in terms of IPs or accuracy for final word identification in highly predictable sentences. Our results also showed that, among EHA users, greater working memory capacity was associated with earlier IPs and improved accuracy in consonant and word identification. Together, our findings demonstrate that the gated speech perception ability of EHA users was not at the level of ENH individuals, in terms of IPs and accuracy. In addition, gated speech perception was more cognitively demanding for EHA users than for ENH individuals in the absence of semantic context. © The Author(s) 2014.

  2. An impaired health related muscular fitness contributes to a reduced walking capacity in patients with schizophrenia: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Patients with schizophrenia report muscle weakness. The relation of this muscle weakness with performing daily life activities such as walking is however not yet studied. The aim of this study was to quantify walking capacity and health related muscular fitness in patients with schizophrenia compared with age-, gender and body mass index (BMI)-matched healthy controls. Secondly, we identified variables that could explain the variability in walking capacity and in health related muscular fitness in patients with schizophrenia. Methods A total of 100 patients with schizophrenia and 40 healthy volunteers were initially screened. Eighty patients with schizophrenia (36.8±10.0 years) and the 40 age-, gender- and body mass index (BMI)-matched healthy volunteers (37.1±10.3 years) were finally included. All participants performed a standing broad jump test (SBJ) and a six-minute walk test (6MWT) and filled out the International Physical Activity Questionnaire. Patients additionally had a fasting metabolic laboratory screening and were assessed for psychiatric symptoms. Results Patients with schizophrenia did have lower 6MWT (17.9%, p<0.001) [effect size (ES)=−1.01] and SBJ (14.1%, p<0.001) (ES=−0.57) scores. Patients were also less physically active (1291.0±1201.8 metabolic equivalent-minutes/week versus 2463.1±1365.3, p<0.001) (ES=−0.91) than controls. Schizophrenia patients with metabolic syndrome (MetS) (35%) had a 23.9% lower (p<0.001) SBJ-score and 22.4% (p<0.001) lower 6MWT-score than those without MetS. In multiple regression analysis, 71.8% of the variance in 6MWT was explained by muscular fitness, BMI, presence of MetS and physical activity participation, while 53.9% of the variance in SBJ-score was explained by age, illness duration, BMI and physical activity participation. Conclusions The walking capacity and health-related muscular fitness are impaired in patients with schizophrenia and both should be a major focus in daily clinical practice

  3. Activated hepatic stellate cells impair NK cell anti-fibrosis capacity through a TGF-β-dependent emperipolesis in HBV cirrhotic patients

    PubMed Central

    Shi, Jijing; Zhao, Juanjuan; Zhang, Xin; Cheng, Yongqian; Hu, Jinhua; Li, Yuanyuan; Zhao, Xin; Shang, Qinghua; Sun, Yanling; Tu, Bo; Shi, Lei; Gao, Bin; Wang, Fu-Sheng; Zhang, Zheng

    2017-01-01

    Natural killer (NK) cells can induce liver fibrosis remission by killing hepatic stellate cells (HSCs) and producing interferon (IFN)-γ in a mouse model; however, their anti-fibrotic immune-characteristics and regulatory mechanisms by HSCs remain to be determined, especially in livers from HBV-infected liver cirrhosis (LC) patients. We analyzed frequency, phenotype and anti-fibrotic function of hepatic and peripheral NK subsets in 43 HBV-LC patients. We found that hepatic NK subsets from LC patients displayed a decreased frequency, activation status and anti-fibrotic activity compared with those from chronic hepatitis B patients, which were mainly mediated by increased intrahepatic tumour-growth factor (TGF)-β because blockade of TGF-β significantly reversed NK anti-fibrotic function in vitro. In vivo, hepatic NK cells were enriched in proximity to the α-smooth muscle actin (α-SMA+) area within mild fibrosis regions; while in severe fibrotic areas, they were either directly attached to or separated from the α-SMA+ region. NK cells from LC patients could enter HSCs to form emperipolesis (a cell-in-cell structure) and become apoptotic; anti-TGF-β treatment ameliorated this emperipolesis. This finding suggested a novel mechanism by which activated HSCs impair NK cells’ anti-fibrosis capacity through a TGF-β-dependent emperipolesis in LC patients, providing an anti-fibrotic rational by enhancing NK cell activity. PMID:28291251

  4. A retroactive spatial cue improved VSTM capacity in mild cognitive impairment and medial temporal lobe amnesia but not in healthy older adults.

    PubMed

    Newsome, Rachel N; Duarte, Audrey; Pun, Carson; Smith, Victoria M; Ferber, Susanne; Barense, Morgan D

    2015-10-01

    Visual short-term memory (VSTM) is a vital cognitive ability, connecting visual input with conscious awareness. VSTM performance declines with mild cognitive impairment (MCI) and medial temporal lobe (MTL) amnesia. Many studies have shown that providing a spatial retrospective cue ("retrocue") improves VSTM capacity estimates for healthy young adults. However, one study has demonstrated that older adults are unable to use a retrocue to inhibit irrelevant items from memory. It is unknown whether patients with MCI and MTL amnesia will be able to use a retrocue to benefit their memory. We administered a retrocue and a baseline (simultaneous cue, "simucue") task to young adults, older adults, MCI patients, and MTL cases. Consistent with previous findings, young adults showed a retrocue benefit, whereas healthy older adults did not. In contrast, both MCI patients and MTL cases showed a retrocue benefit--the use of a retrocue brought patient performance up to the level of age-matched controls. We speculate that the patients were able to use the spatial information from the retrocue to reduce interference and facilitate binding items to their locations.

  5. Activated hepatic stellate cells impair NK cell anti-fibrosis capacity through a TGF-β-dependent emperipolesis in HBV cirrhotic patients.

    PubMed

    Shi, Jijing; Zhao, Juanjuan; Zhang, Xin; Cheng, Yongqian; Hu, Jinhua; Li, Yuanyuan; Zhao, Xin; Shang, Qinghua; Sun, Yanling; Tu, Bo; Shi, Lei; Gao, Bin; Wang, Fu-Sheng; Zhang, Zheng

    2017-03-14

    Natural killer (NK) cells can induce liver fibrosis remission by killing hepatic stellate cells (HSCs) and producing interferon (IFN)-γ in a mouse model; however, their anti-fibrotic immune-characteristics and regulatory mechanisms by HSCs remain to be determined, especially in livers from HBV-infected liver cirrhosis (LC) patients. We analyzed frequency, phenotype and anti-fibrotic function of hepatic and peripheral NK subsets in 43 HBV-LC patients. We found that hepatic NK subsets from LC patients displayed a decreased frequency, activation status and anti-fibrotic activity compared with those from chronic hepatitis B patients, which were mainly mediated by increased intrahepatic tumour-growth factor (TGF)-β because blockade of TGF-β significantly reversed NK anti-fibrotic function in vitro. In vivo, hepatic NK cells were enriched in proximity to the α-smooth muscle actin (α-SMA+) area within mild fibrosis regions; while in severe fibrotic areas, they were either directly attached to or separated from the α-SMA+ region. NK cells from LC patients could enter HSCs to form emperipolesis (a cell-in-cell structure) and become apoptotic; anti-TGF-β treatment ameliorated this emperipolesis. This finding suggested a novel mechanism by which activated HSCs impair NK cells' anti-fibrosis capacity through a TGF-β-dependent emperipolesis in LC patients, providing an anti-fibrotic rational by enhancing NK cell activity.

  6. Beyond capacity limitations II: Effects of lexical processes on word recall in verbal working memory tasks in children with and without specific language impairment

    PubMed Central

    Mainela-Arnold, Elina; Evans, Julia L.; Coady, Jeffry

    2010-01-01

    Purpose This study investigated the impact of lexical processes on target word recall in sentence span tasks in children with and without specific language impairment (SLI). Method Participants were 42 children (ages 8;2–12;3), 21 with SLI and 21 typically developing peers matched on age and nonverbal IQ. Children completed a sentence span task where target words to be recalled varied in word frequency and neighborhood density. Two measures of lexical processes were examined, the number of non-target competitor words activated during a gating task (lexical cohort competition) and word definitions. Results Neighborhood density had no effect on word recall for either group. However, both groups recalled significantly more high than low frequency words. Lexical cohort competition and specificity of semantic representations accounted for unique variance in the number of target word recalled in the SLI and CA groups combined. Conclusions Performance on verbal working memory span tasks for both SLI and CA children is influenced by word frequency, lexical cohorts, and semantic representations. Future studies need to examine the extent to which verbal working memory capacity is a cognitive construct independent of extant language knowledge representations. PMID:20705747

  7. Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

    PubMed

    Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

    2016-02-01

    Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5

  8. Drug-binding properties of rat alpha 1-foetoprotein. Binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid.

    PubMed Central

    Hervé, F; Rajkowski, K; Martin, M T; Dessen, P; Cittanova, N

    1984-01-01

    As part of an investigation into whether alpha 1-foetoprotein (alpha 1-FP) plays the same transport role in foetal serum as albumin does in the adult, the binding properties of both proteins were compared with respect to the binding of a series of compounds known to be bound by albumin's specific drug-binding sites. The binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid by rat alpha 1-FP and serum albumin was studied by equilibrium dialysis at 4 degrees C. Rat alpha 1-FP was shown to have neither albumin's high-affinity site II (diazepam as marker) nor its site III (digitoxin and cholic acid as markers). High-affinity binding by alpha 1-FP was found for the specific markers (warfarin, phenylbutazone, azapropazone) of albumin's drug-binding site I. However, instead of albumin's one high-affinity site/molecule, a mean value of 0.5 site/molecule was obtained with rat alpha 1-FP. Charcoal treatment at neutral pH of rat serum albumin did not affect its measured binding properties, but treatment of the alpha 1-FP led to an increased affinity for warfarin, phenylbutazone and azapropazone without a change in the measured number of sites, indicating competition for binding at this site by (an) endogenous ligand(s). These results are discussed in terms of the structures of the two proteins and with respect to the physiological implications of the differences found. PMID:6206846

  9. Drug-binding energetics of human α-1-acid glycoprotein assessed by isothermal titration calorimetry and molecular docking simulations

    PubMed Central

    Huang, Johnny X.; Cooper, Matthew A.; Baker, Mark A.; Azad, Mohammad A.K.; Nation, Roger L.; Li, Jian; Velkov, Tony

    2012-01-01

    This study utilizes sensitive, modern isothermal titration calorimetric (ITC) methods to characterize the microscopic thermodynamic parameters that drive the binding of basic drugs to α-1-acid glycoprotein (AGP) and thereby rationalize the thermodynamic data in relation to docking models and crystallographic structures of the drug-AGP complexes. The binding of basic compounds from the tricyclic antidepressant series, together with miaserine, chlorpromazine, disopyramide and cimetidine all displayed an exothermically driven binding interaction with AGP. The impact of protonation/deprotonation events, ionic strength, temperature and the individual selectivity of the A and F1*S AGP variants on drug-binding thermodynamics were characterized. A correlation plot of the thermodynamic parameters for all of the test compounds revealed enthalpy-entropy compensation is in effect. The exothermic binding energetics of the test compounds were driven by a combination of favorable (negative) enthalpic (ΔH°) and favorable (positive) entropic (ΔS°) contributions to the Gibbs free energy (ΔG°). Collectively, the data imply that the free energies that drive drug binding to AGP and its relationship to drug-serum residency evolve from the complex interplay of enthalpic and entropic forces from interactions with explicit combinations of hydrophobic and polar side-chain sub-domains within the multi-lobed AGP ligand binding cavity. PMID:23192962

  10. A comprehensive analysis of the influence of drug binding kinetics on drug action at molecular and systems levels.

    PubMed

    Yin, Ning; Pei, Jianfeng; Lai, Luhua

    2013-06-01

    Binding kinetics is closely related to the efficacy of drugs. Several aspects of binding kinetics, such as long residence or frequent dissociation, have been proposed to affect drug properties such as efficacy, selectivity, and multi-target potency. However, a comprehensive and balanced study of binding kinetics in various scenarios is still needed. We performed a comprehensive computational analysis of the role of drug binding kinetics in various situations such as enzyme inhibition, receptor binding, multi-target drug targeting, signal transduction pathways, and metabolic networks. Molecular studies of enzyme inhibition, receptor binding, and multi-target drugs have shown that at constant binding affinity, fast associating drugs show better enzyme inhibitory effects, earlier and higher receptor occupancy peaks, and better multi-target performances, while slow dissociating drugs show prolonged receptor occupancy, as suggested by others. Different situations exemplify slightly different kinetic-efficacy relationships, and each must be considered separately. At the systems level, binding kinetics can not only change the overall effect of drugs, but can also affect signaling dynamics. For example, in the tumor necrosis factor α-induced nuclear factor-κB pathway, inhibitor addition can delay the onset of oscillations and decrease their frequencies, with these changes varying with the binding kinetics of the inhibitor. The effects of drug binding kinetics also depend on network topology and where the target is located in the network. For successful drug discovery, both molecular binding kinetics and systems level requirements need to be considered.

  11. Computational Assay of H7N9 Influenza Neuraminidase Reveals R292K Mutation Reduces Drug Binding Affinity

    NASA Astrophysics Data System (ADS)

    Woods, Christopher J.; Malaisree, Maturos; Long, Ben; McIntosh-Smith, Simon; Mulholland, Adrian J.

    2013-12-01

    The emergence of a novel H7N9 avian influenza that infects humans is a serious cause for concern. Of the genome sequences of H7N9 neuraminidase available, one contains a substitution of arginine to lysine at position 292, suggesting a potential for reduced drug binding efficacy. We have performed molecular dynamics simulations of oseltamivir, zanamivir and peramivir bound to H7N9, H7N9-R292K, and a structurally related H11N9 neuraminidase. They show that H7N9 neuraminidase is structurally homologous to H11N9, binding the drugs in identical modes. The simulations reveal that the R292K mutation disrupts drug binding in H7N9 in a comparable manner to that observed experimentally for H11N9-R292K. Absolute binding free energy calculations with the WaterSwap method confirm a reduction in binding affinity. This indicates that the efficacy of antiviral drugs against H7N9-R292K will be reduced. Simulations can assist in predicting disruption of binding caused by mutations in neuraminidase, thereby providing a computational `assay.'

  12. Profiling of drug binding proteins by monolithic affinity chromatography in combination with liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Xuepei; Wang, Tongdan; Zhang, Hanzhi; Han, Bing; Wang, Lishun; Kang, Jingwu

    2014-09-12

    A new approach for proteome-wide profiling drug binding proteins by using monolithic capillary affinity chromatography in combination with HPLC-MS/MS is reported. Two immunosuppresive drugs, namely FK506 and cyclosporin A, were utilized as the experimental models for proof-of-concept. The monolithic capillary affinity columns were prepared through a single-step copolymerization of the drug derivatives with glycidyl methacrylate and ethylene dimethacrylate. The capillary chromatography with the affinity monolithic column facilitates the purification of the drug binding proteins from the cell lysate. By combining the capillary affinity column purification and the shot-gun proteomic analysis, totally 33 FK506- and 32 CsA-binding proteins including all the literature reported target proteins of these two drugs were identified. Among them, two proteins, namely voltage-dependent anion-selective channel protein 1 and serine/threonine-protein phosphatase PGAM5 were verified by using the recombinant proteins. The result supports that the monolithic capillary affinity chromatography is likely to become a valuable tool for profiling of binding proteins of small molecular drugs as well as bioactive compounds.

  13. Maternal effects and population regulation: maternal density-induced reproduction suppression impairs offspring capacity in response to immediate environment in root voles Microtus oeconomus.

    PubMed

    Bian, Jiang-Hui; Du, Shou-Yang; Wu, Yan; Cao, Yi-Fan; Nie, Xu-Heng; He, Hui; You, Zhi-Bing

    2015-03-01

    FCM elevations, reproduction suppression and body mass decrease at sexual maturity in offspring. The FCM elevations and reproduction suppression were independent of offspring population density and correlated with decreased offspring quality. These findings indicate that intrinsic state alterations induced by maternal stress impair offspring capacity in response to immediate environment, and these alterations are likely mediated by maternal stress system. The maladaptive reproduction suppression seen in HL group suggests intrinsic population density as one of ecological factors generating delayed density-dependent effects.

  14. Water participation in molecular recognition and protein-ligand association: Probing the drug binding site "Sudlow I" in human serum albumin

    NASA Astrophysics Data System (ADS)

    Al-Lawatia, Najla; Steinbrecher, Thomas; Abou-Zied, Osama K.

    2012-03-01

    Human serum albumin (HSA) plays an important role in the transport and disposition of endogenous and exogenous ligands present in blood. Its capacity to reversibly bind a large variety of drugs results in its prevailing role in drug pharmacokinetics and pharmacodynamics. In this work, we used 7-hydroxyquinoline (7HQ) as a probe to study the binding nature of one of the major drug binding sites of HSA (Sudlow I) and to reveal the local environment around the probe in the binding site. The interaction between 7HQ and HSA at a physiological pH of 7.2 was investigated using steady-state and lifetime spectroscopic measurements, molecular docking and molecular dynamics (MD) simulations methods. The fluorescence results indicate a selective interaction between 7HQ and the Trp214 residue. The reduction in both the intensity and lifetime of the Trp214 fluorescence upon probe binding indicates the dominant role of static quenching. Molecular docking and MD simulations show that 7HQ binds in Sudlow site I close to Trp214, confirming the experimental results, and pinpoint the dominant role of hydrophobic interaction in the binding site. Electrostatic interactions were also found to be important in which two water molecules form strong hydrogen bonds with the polar groups of 7HQ. Detection of water in the binding site agrees with the absorption and fluorescence results that show the formation of a zwitterion tautomer of 7HQ. The unique spectral signatures of 7HQ in water make this molecule a potential probe for detecting the presence of water in nanocavities of proteins. Interaction of 7HQ with water in the binding site shows that water molecules can be crucial for molecular recognition and association in protein binding sites.

  15. Drug binding to human serum albumin: abridged review of results obtained with high-performance liquid chromatography and circular dichroism.

    PubMed

    Ascoli, Giorgio A; Domenici, Enrico; Bertucci, Carlo

    2006-09-01

    The drug binding to plasma and tissue proteins are fundamental factors in determining the overall pharmacological activity of a drug. Human serum albumin (HSA), together with alpha1-acid glycoprotein (AGP), are the most important plasma proteins, which act as drug carriers, with drug pharmacokinetic implications, resulting in important clinical impacts for drugs that have a relatively narrow therapeutic index. This review focuses on the combination of biochromatography and circular dichroism as an effective approach for the characterization of albumin binding sites and their enantioselectivity. Furthermore, their applications to the study of changes in the binding properties of the protein arising by the reversible or covalent binding of drugs are discussed, and examples of physiological relevance reported. Perspectives of these studies reside in supporting the development of new drugs, which require miniaturization to facilitate the screening of classes of compounds for their binding to the target protein, and a deeper characterization of the mechanisms involved in the molecular recognition processes.

  16. A fluorescent reporter detects details of aromatic ligand interference in drug-binding sites of human serum albumin.

    PubMed

    Dobretsov, Gennady; Smolina, Natalia; Syrejshchikova, Tatiana; Brilliantova, Varvara; Uzbekov, Marat

    2016-09-09

    Human serum albumin (HSA) transports many ligands including small aromatic molecules: metabolites, drugs etc. Phenylbutazone is an anti-inflammatory drug, which binds to the drug-binding site I of HSA. Its interaction with this site has been studied using a fluorescent dye, CAPIDAN, whose fluorescence in serum originates from HSA and is sensitive to the changes in HSA site I in some diseases. Its fluorescence in HSA solutions is strongly suppressed by phenylbutazone. This phenomenon seems to be a basic sign of a simple drug-dye competition. However, a more detailed study of the time-resolved fluorescence decay of CAPIDAN has shown that phenylbutazone lowers fluorescence without changing the total amount of bound dye. In brief, the HSA-bound dye forms three populations due to three types of environment at the binding sites. The first two populations probably have a rather strong Coulomb interaction with the positive charge of residues Arginine 218 or Arginine 222 in site I and are responsible for approximately 90% of the total fluorescence. Phenylbutazone blocks this interaction and therefore lowers this fluorescence. At the same time the binding of the third population increases considerably in the presence of phenylbutazone, and, as a result, the actual number of bound dye molecules remains almost unchanged despite the ligand competition. So, time resolved fluorescence of the reporter allows to observe details of interactions and interference of aromatic ligands in drug binding site I of HSA both in isolated HSA and in serum. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Ligand- and drug-binding studies of membrane proteins revealed through circular dichroism spectroscopy.

    PubMed

    Siligardi, Giuliano; Hussain, Rohanah; Patching, Simon G; Phillips-Jones, Mary K

    2014-01-01

    A great number of membrane proteins have proven difficult to crystallise for use in X-ray crystallographic structural determination or too complex for NMR structural studies. Circular dichroism (CD) is a fast and relatively easy spectroscopic technique to study protein conformational behaviour. In this review examples of the applications of CD and synchrotron radiation CD (SRCD) to membrane protein ligand binding interaction studies are discussed. The availability of SRCD has been an important advancement in recent progress, most particularly because it can be used to extend the spectral region in the far-UV region (important for increasing the accuracy of secondary structure estimations) and for working with membrane proteins available in only small quantities for which SRCD has facilitated molecular recognition studies. Such studies have been accomplished by probing in the near-UV region the local tertiary structure of aromatic amino acid residues upon addition of chiral or non-chiral ligands using long pathlength cells of small volume capacity. In particular, this review describes the most recent use of the technique in the following areas: to obtain quantitative data on ligand binding (exemplified by the FsrC membrane sensor kinase receptor); to distinguish between functionally similar drugs that exhibit different mechanisms of action towards membrane proteins (exemplified by secretory phospholipase A2); and to identify suitable detergent conditions to observe membrane protein-ligand interactions using stabilised proteins (exemplified by the antiseptic transporter SugE). Finally, the importance of characterising in solution the conformational behaviour and ligand binding properties of proteins in both far- and near-UV regions is discussed. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding. © 2013.

  18. Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults.

    PubMed

    Menegaux, Aurore; Meng, Chun; Neitzel, Julia; Bäuml, Josef G; Müller, Hermann J; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra M; Finke, Kathrin; Sorg, Christian

    2017-04-15

    Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery

  19. Beyond Capacity Limitations II: Effects of Lexical Processes on Word Recall in Verbal Working Memory Tasks in Children with and without Specific Language Impairment

    ERIC Educational Resources Information Center

    Mainela-Arnold, Elina; Evans, Julia L.; Coady, Jeffry

    2010-01-01

    Purpose: This study investigated the impact of lexical processes on target word recall in sentence span tasks in children with and without specific language impairment (SLI). Method: Participants were 42 children (ages 8;2-12;3 [years;months]): 21 with SLI and 21 typically developing peers matched on age and nonverbal IQ. Children completed a…

  20. Beyond Capacity Limitations II: Effects of Lexical Processes on Word Recall in Verbal Working Memory Tasks in Children with and without Specific Language Impairment

    ERIC Educational Resources Information Center

    Mainela-Arnold, Elina; Evans, Julia L.; Coady, Jeffry

    2010-01-01

    Purpose: This study investigated the impact of lexical processes on target word recall in sentence span tasks in children with and without specific language impairment (SLI). Method: Participants were 42 children (ages 8;2-12;3 [years;months]): 21 with SLI and 21 typically developing peers matched on age and nonverbal IQ. Children completed a…

  1. Probing kinetic drug binding mechanism in voltage-gated sodium ion channel: open state versus inactive state blockers.

    PubMed

    Pal, Krishnendu; Gangopadhyay, Gautam

    2015-01-01

    The kinetics and nonequilibrium thermodynamics of open state and inactive state drug binding mechanisms have been studied here using different voltage protocols in sodium ion channel. We have found that for constant voltage protocol, open state block is more efficient in blocking ionic current than inactive state block. Kinetic effect comes through peak current for mexiletine as an open state blocker and in the tail part for lidocaine as an inactive state blocker. Although the inactivation of sodium channel is a free energy driven process, however, the two different kinds of drug affect the inactivation process in a different way as seen from thermodynamic analysis. In presence of open state drug block, the process initially for a long time remains entropy driven and then becomes free energy driven. However in presence of inactive state block, the process remains entirely entropy driven until the equilibrium is attained. For oscillating voltage protocol, the inactive state blocking is more efficient in damping the oscillation of ionic current. From the pulse train analysis it is found that inactive state blocking is less effective in restoring normal repolarisation and blocks peak ionic current. Pulse train protocol also shows that all the inactive states behave differently as one inactive state responds instantly to the test pulse in an opposite manner from the other two states.

  2. Characterization of the comparative drug binding to intra- (liver fatty acid binding protein) and extra- (human serum albumin) cellular proteins.

    PubMed

    Rowland, Andrew; Hallifax, David; Nussio, Matthew R; Shapter, Joseph G; Mackenzie, Peter I; Brian Houston, J; Knights, Kathleen M; Miners, John O

    2015-01-01

    1. This study compared the extent, affinity, and kinetics of drug binding to human serum albumin (HSA) and liver fatty acid binding protein (LFABP) using ultrafiltration and surface plasmon resonance (SPR). 2. Binding of basic and neutral drugs to both HSA and LFABP was typically negligible. Binding of acidic drugs ranged from minor (fu > 0.8) to extensive (fu < 0.1). Of the compounds screened, the highest binding to both HSA and LFABP was observed for the acidic drugs torsemide and sulfinpyrazone, and for β-estradiol (a polar, neutral compound). 3. The extent of binding of acidic drugs to HSA was up to 40% greater than binding to LFABP. SPR experiments demonstrated comparable kinetics and affinity for the binding of representative acidic drugs (naproxen, sulfinpyrazone, and torsemide) to HSA and LFABP. 4. Simulations based on in vitro kinetic constants derived from SPR experiments and a rapid equilibrium model were undertaken to examine the impact of binding characteristics on compartmental drug distribution. Simulations provided mechanistic confirmation that equilibration of intracellular unbound drug with the extracellular unbound drug is attained rapidly in the absence of active transport mechanisms for drugs bound moderately or extensively to HSA and LFABP.

  3. Effect of X-irradiation on epidermal immune function: decreased density and alloantigen-presenting capacity of Ia+ Langerhans cells and impaired production of epidermal cell-derived thymocyte activating factor (ETAF)

    SciTech Connect

    Breathnach, S.M.; Katz, S.I.

    1985-12-01

    The mechanisms involved in the modulation of cutaneous immune responses by x-irradiation on epidermal immune function. We therefore investigated the effect of x-irradiation of mice on: (a) the density of epidermal Ia+ Langerhans cells (LC) in immunofluorescence studies, (b) epidermal cell (EC) allostimulatory capacity in the allogeneic EC-lymphocyte reaction (ELR), and (c) production of epidermal cell-derived thymocyte activating factor (ETAF). C3H/He and BALB/c mice were irradiated with 900, 1800, 2700, or 3600 rad from a /sup 137/Cs source, and sacrificed 10 h or 3 days later. X-irradiation of mice 10 h previously only slightly decreased the density of epidermal Ia+ LC and did not affect the capacity of their EC to stimulate allogeneic responder lymphocytes in the ELR. X-irradiation of mice 3 days previously, however, resulted in a dose-dependent decrease in the density of Ia+ LC. This decrease was accompanied by a substantial reduction in EC allostimulatory capacity in the ELR at all doses of x-irradiation. ETAF production by cultured EC from mice x-irradiated 3 days previously was also found to be diminished at all doses of x-irradiation. Trypan blue exclusion studies demonstrated that the observed decreases in EC allostimulatory capacity and ETAF production were not the result of a generalized lethal effect of x-irradiation on EC. The reduction in EC allostimulatory capacity following in vivo x-irradiation could not be reversed by addition of exogenous ETAF or interleukin-1 in the ELR. Taken together, these results indicate that x-irradiation decreases the density of Ia+ LC, impairs LC alloantigen-presenting function, and reduces ETAF production. Thus cutaneous x-irradiation may affect inflammatory and neoplastic processes not only by its antimitotic activity, but also by a direct effect on EC which subserve immunologic functions.

  4. Eight-Week Training Cessation Suppresses Physiological Stress but Rapidly Impairs Health Metabolic Profiles and Aerobic Capacity in Elite Taekwondo Athletes

    PubMed Central

    Liao, Yi-Hung; Sung, Yu-Chi

    2016-01-01

    Changes in an athlete’s physiological and health metabolic profiles after detraining have not been studied in elite Taekwondo (TKD) athletes. To enable a better understanding of these physiological changes to training cessation, this study examined the effects of 8-weeks detraining on the aerobic capacity, body composition, inflammatory status and health metabolic profile in elite TKD athletes. Sixteen elite TKD athletes (age: 21.0 ± 0.8 yrs, BMI: 22.4 ± 3.9 kg/m2; Mean ± SD; 11 males and 5 females) participated in this study. Physical activity level assessment using computerized physical activity logs was performed during the competitive preparation season (i.e. one-week before national competition) and at two week intervals throughout the detraining period. Participant aerobic capacity, body fat, and blood biomarkers were measured before and after detraining, and the blood biomarker analyses included leukocyte subpopulations, blood glucose, insulin, dehydroepiandrosterone-sulfate (DHEA-S), and cortisol. Eight-week detraining increased DHEA-S/cortisol ratio (+57.3%, p = 0.004), increased insulin/cortisol ratio (+59.9%, p = 0.004), reduced aerobic power (–2.43%, p = 0.043), increased body fat accumulation (body fat%: +21.3%, p < 0.001), decreased muscle mass (muscle mass%: –4.04%, p < 0.001), and elevated HOMA-IR (the biomarker of systemic insulin resistance; +34.2%, p = 0.006). The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory index, increased by 48.2% (p = 0.005). The change in aerobic capacity was correlated with the increased fat mass (r = –0.429, p = 0.049) but not with muscle loss. An increase in the NLR was correlated to the changes in HOMA-IR (r = 0.44, p = 0.044) and aerobic capacity (r = –0.439, p = 0.045). We demonstrate that 8-week detraining suppresses physiological stress but rapidly results in declines in athletic performance and health metabolic profiles, including reduced aerobic capacity, increased body fat, muscle

  5. Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents.

    PubMed

    Gjerden, Pål; Slørdal, Lars; Bramness, Jørgen G

    2009-12-01

    The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

  6. Vanadate trapping of nucleotide at the ATP-binding sites of human multidrug resistance P-glycoprotein exposes different residues to the drug-binding site

    PubMed Central

    Loo, Tip W.; Clarke, David M.

    2002-01-01

    The human multidrug resistance P-glycoprotein uses ATP to transport a wide variety of structurally unrelated cytotoxic compounds out of the cell. In this study, we used cysteine-scanning mutagenesis and cross-linking studies to identify residues that are exposed to the drug-binding site upon vanadate trapping. In the absence of nucleotides, C222(TM4) was cross-linked to C868(TM10) and C872(TM10); C306(TM5) was cross-linked to C868(TM10), C872(TM10), C945(TM11), C982(TM12), and C984(TM12); and C339(TM6) was cross-linked to C868(TM10), C872(TM10), C942(TM11), C982(TM12), and C985(TM12). These cysteines are in the middle of the predicted transmembrane (TM) segments and form the drug-binding site. Cross-linking between 332C(TM6) and cysteines introduced at the extracellular side of other TM segments was also done. In the absence of nucleotides, residues 332C and 856C on the extracellular side of TMs 6 and 10, respectively, were cross-linked with a 13-Å cross-linker (M8M, 3,6-dioxaoctane-1,8-diyl bismethanethiosulfonate). ATP plus vanadate inhibited cross-linking between 332C(TM6) and 856C(TM10) as well as those in the drug-binding site. Instead, vanadate trapping promoted cross-linking between 332C(TM6) and 976C(TM12) with a 10-Å cross-linker (M6M, 1,6-hexanediyl bismethanethiosulfonate). When ATP hydrolysis was allowed to proceed, then 332C(TM12) could form a disulfide bond with 975C(TM12). The cross-linking pattern of 332C(TM6) with residues in TM10 and TM12 indicates that the drug-binding site undergoes dynamic and relatively large conformational changes, and that different residues are exposed to the drug-binding site during the resting phase, upon vanadate trapping and at the completion of the catalytic cycle. PMID:11891276

  7. Elevated Pulmonary Arterial and Systemic Plasma Aldosterone Levels Associate with Impaired Cardiac Reserve Capacity during Exercise in Left Ventricular Systolic Heart Failure Patients: A Pilot Study

    PubMed Central

    Maron, Bradley A.; Stephens, Thomas E.; Farrell, Laurie A.; Oldham, William M.; Loscalzo, Joseph; Leopold, Jane A.; Lewis, Gregory D.

    2015-01-01

    Background Elevated levels of aldosterone are a modifiable contributor to clinical worsening in heart failure with reduced ejection fraction (HFrEF). Endothelin-1 (ET-1), which is increased in HFrEF, induces pulmonary endothelial aldosterone synthesis in vitro. However, whether transpulmonary aldosterone release occurs in humans or aldosterone relates to functional capacity in HFrEF is not known. Therefore, we aim to characterize ET-1 and transpulmonary aldosterone levels in HFrEF, and determine if aldosterone levels relate to peak volume of oxygen uptake (pVO2). Methods Data from 42 consecutive HFrEF patients and 18 controls referred for invasive cardiopulmonary exercise testing were analyzed retrospectively. Results Radial ET-1 levels were higher in HFrEF patients compared to controls (17.5 [11.5–31.4] vs. 11.5 [4.4–19.0] pg/ml, p=0.04). A significant ET-1 transpulmonary gradient (pulmonary arterial [PA] - radial arterial levels) was present in HFrEF (P<0.001), but not in controls (P=0.24). Compared to controls, aldosterone levels were increased in HFrEF patients in the PA (364 [250–489] vs. 581 [400–914] ng/dl, P<0.01) and radial compartments (366 [273–466] vs. 702 [443–1223] ng/dl, P<0.001). Akin to ET-1, a transpulmonary increase in aldosterone concentration was also observed between controls and HFrEF patients at rest (7.5 [−54–40] vs. 61.6 [−13.6–165] ng/dl, P=0.01) and peak exercise (−20.7 [−39.6–79.1] vs. +25.8 [−29.2–109.3] ng/dl, P=0.02). The adjusted pVO2 correlated inversely with aldosterone levels at peak activity in the PA (r=−0.31, P=0.01) and radial artery (r=−0.32, P=0.01). Conclusions These data provide preliminary evidence in support of increased transpulmonary aldosterone levels in HFrEF and suggest an inverse relationship between circulating aldosterone and pVO2. Future prospective studies are needed to characterize the functional effects of transpulmonary and circulating aldosterone on cardiac reserve

  8. Brain perfusion imaging under acetazolamide challenge for detection of impaired cerebrovascular reserve capacity: positive findings with O-15-water PET in patients with negative Tc-99m-HMPAO SPECT.

    PubMed

    Acker, Güliz; Lange, Catharina; Schatka, Imke; Pfeifer, Andreas; Czabanka, Marcus A; Vajkoczy, Peter; Buchert, Ralph

    2017-07-20

    Cerebrovascular reserve capacity (CVRC) is an important parameter for treatment decisions in chronic cerebrovascular diseases. It can be assessed by measuring the acetazolamide-induced change of regional cerebral blood flow using single photon emission computed tomography (SPECT) with Tc-99m-labeled hexamethylpropyleneamine oxime (HMPAO) or positron emission tomography (PET) with O-15-water. Methods: Our database was searched for patients with moyamoya vasculopathy (MMV) or atherosclerotic cerebrovascular disease who had underwent O-15-water PET after normal Tc-99m-HMPAO SPECT with respect to CVRC. O-15-water PET was analyzed visually and quantitatively. Quantitative analysis was based on parametric CVRC maps generated by voxel-wise image subtraction. Results: The search identified 18 patients (43±15y, 12 MMV). PET revealed impaired CVRC in 8 patients (44%). Quantitative analysis confirmed the positive visual findings in O-15-water PET and the negative findings in Tc-99m-HMPAO SPECT. Conclusion: O-15-water PET enables detection of impaired CVRC in a considerable fraction of symptomatic patients with steno-occlusion and negative Tc-99m-HMPAO SPECT. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  9. Interactions of human P-glycoprotein transport substrates and inhibitors at the drug binding domain: Functional and molecular docking analyses.

    PubMed

    Kadioglu, Onat; Saeed, Mohamed E M; Valoti, Massimo; Frosini, Maria; Sgaragli, Giampietro; Efferth, Thomas

    2016-03-15

    Rhodamine 123 (R123) transport substrate sensitizes P-glycoprotein (P-gp) to inhibition by compound 2c (cis-cis) N,N-bis(cyclohexanolamine)aryl ester isomer in a concentration-dependent manner in human MDR1-gene transfected mouse T-lymphoma L5178 cells as shown previously. By contrast, epirubicin (EPI) concentration changes left unaltered 2c IC50 values of EPI efflux. To clarify this discrepancy, defined molecular docking (DMD) analyses of 12 N,N-bis(cyclohexanolamine)aryl esters, the highly flexible aryl ester analog 4, and several P-gp substrate/non-substrate inhibitors were performed on human P-gp drug- or nucleotide-binding domains (DBD or NBD). DMD measurements yielded lowest binding energy (LBE, kcal/mol) values (mean ± SD) ranging from -11.8 ± 0.54 (valspodar) to -3.98 ± 0.01 (4). Lys234, Ser952 and Tyr953 residues formed H-bonds with most of the compounds. Only 2c docked also at ATP binding site (LBE value of -6.9 ± 0.30 kcal/mol). Inhibition of P-gp-mediated R123 efflux by 12 N,N-bis(cyclohexanolamine)aryl esters and 4 significantly correlated with LBE values. DMD analysis of EPI, (3)H-1EPI, (3)H-2EPI, (14)C-1EPI, (14)C-2EPI, R123 and 2c before and after previous docking of each of them indicated that pre-docking of either 2c or EPI significantly reduced LBE of both EPI and R123, and that of both (3)H-2EPI and (14)C-2EPI, respectively. Since the clusters of DBD amino acid residues interacting with EPI were different, if EPI docked alone or after pre-docking of EPI or 2c, the existence of alternative secondary binding site for EPI on P-gp is credible. In conclusion, 2c may allocate the drug-binding pocket and reduce strong binding of EPI and R123 in agreement with P-gp inhibition experiments, where 2c reduced efflux of EPI and R123.

  10. New insights into non-enzymatic glycation of human serum albumin biopolymer: A study to unveil its impaired structure and function.

    PubMed

    Raghav, Alok; Ahmad, Jamal; Alam, Khursheed; Khan, Asad U

    2017-03-18

    Albumin glycation and subsequent formation of advanced glycation end products (AGEs) correlate with diabetes and associated complications. Human Serum Albumin (HSA) was modified with d-glucose for a 40day period under sterile conditions at 37°C. Modified samples along with native HSA (unmodified) were analyzed for impairment in biochemical characteristics ((fructosamine, carbonyl, thiol, lysine, arginine, hydroxymethyl furfural [HMF] content), electrochemical (electrical conductance), simulated gastric fluid assay, simulated intestinal fluid assay, spectroscopic properties (UV, fluorescence), optical (surface contact angle) and fluid dynamics (viscosity and Stokes radius). Impairment in drug binding capacity of glycosylated-HSA was assessed with molecular docking experiment using metformin. UV-absorbance and fluorescence measurement were performed for drug bound glycated and native-HSA. Extensively modified HSA has been used to study its relevance in diabetes mellitus. Glucose modified-HSA resulted in AGEs formation. It suggests deleterious impairment in biochemical, electrochemical, spectroscopic, optical and fluidity properties of HSA at high concentrations of glucose. The results of the present study can be useful to understand the phenomenon of proteins damage in hyperglycemic conditions.

  11. Biopartitioning micellar chromatography with sodium dodecyl sulfate as a pseudo α(1)-acid glycoprotein to the prediction of protein-drug binding.

    PubMed

    Hadjmohammadi, Mohammadreza; Salary, Mina

    2013-01-01

    A simple and fast method is of urgent need to measure protein-drug binding affinity in order to meet the rapid development of new drugs. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography (MLC) using micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug-protein interactions. In this study, sodium dodecyl sulfate-micellar liquid chromatography (SDS-MLC) was used for the prediction of protein-drug binding based on the similar property of SDS micelles to α(1)-acid glycoprotein (AGP). The relationships between the BMC retention data of a heterogeneous set of 14 basic and neutral drugs and their plasma protein binding parameter were studied and the predictive ability of models was evaluated. Modeling of logk(BMC) of these compounds was established by multiple linear regression (MLR) and second-order polynomial models obtained in two different concentrations (0.07 and 0.09M) of SDS. The developed MLR models were characterized by both the descriptive and predictive ability (R(2)=0.882, R(CV)(2)=0.832 and R(2)=0.840, R(CV)(2)=0.765 for 0.07 and 0.09M SDS, respectively). The p values <0.01 also indicated that the relationships between the protein-drug binding and the logk(BMC) values were statistically significant at the 99% confidence level. The standard error of estimation showed the standard deviation of the regression to be 11.89 and 13.87 for 0.07 and 0.09M, respectively. The application of the developed model to a prediction set demonstrated that the model was also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values were in good agreement with the experimental value.

  12. Structural Insights into Differences in Drug-binding Selectivity between Two Forms of Human α1-Acid Glycoprotein Genetic Variants, the A and F1*S Forms*

    PubMed Central

    Nishi, Koji; Ono, Tomomi; Nakamura, Teruya; Fukunaga, Naoko; Izumi, Miyoko; Watanabe, Hiroshi; Suenaga, Ayaka; Maruyama, Toru; Yamagata, Yuriko; Curry, Stephen; Otagiri, Masaki

    2011-01-01

    Human α1-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type. In this study, we determined the crystal structures of this mutant hAGP alone and complexed with disopyramide (DSP), amitriptyline (AMT), and the nonspecific drug chlorpromazine (CPZ). The crystal structures revealed that the drug-binding pocket on the A variant is located within an eight-stranded β-barrel, similar to that found in the F1*S variant and other lipocalin family proteins. However, the binding region of the A variant is narrower than that of the F1*S variant. In the crystal structures of complexes with DSP and AMT, the two aromatic rings of each drug interact with Phe-49 and Phe-112 at the bottom of the binding pocket. Although the structure of CPZ is similar to those of DSP and AMT, its fused aromatic ring system, which is extended in length by the addition of a chlorine atom, appears to dictate an alternative mode of binding, which explains its nonselective binding to the F1*S and A variant hAGPs. Modeling experiments based on the co-crystal structures suggest that, in complexes of DSP, AMT, or CPZ with the F1*S variant, Phe-114 sterically hinders interactions with DSP and AMT, but not CPZ. PMID:21349832

  13. Characterization of a quinone reductase activity for the mitomycin C binding protein (MRD): Functional switching from a drug-activating enzyme to a drug-binding protein

    PubMed Central

    He, Min; Sheldon, Paul J.; Sherman, David H.

    2001-01-01

    Self-protection in the mitomycin C (MC)-producing microorganism Streptomyces lavendulae includes MRD, a protein that binds MC in the presence of NADH and functions as a component of a unique drug binding-export system. Characterization of MRD revealed that it reductively transforms MC into 1,2-cis-1-hydroxy-2,7-diaminomitosene, a compound that is produced in the reductive MC activation cascade. However, the reductive reaction catalyzed by native MRD is slow, and both MC and the reduced product are bound to MRD for a relatively prolonged period. Gene shuffling experiments generated a mutant protein (MRDE55G) that conferred a 2-fold increase in MC resistance when expressed in Escherichia coli. Purified MRDE55G reduces MC twice as fast as native MRD, generating three compounds that are identical to those produced in the reductive activation of MC. Detailed amino acid sequence analysis revealed that the region around E55 in MRD strongly resembles the second active site of prokaryotic catalase-peroxidases. However, native MRD has an aspartic acid (D52) and a glutamic acid (E55) residue at the positions corresponding to the catalytic histidine and a nearby glycine residue in the catalase-peroxidases. Mutational analysis demonstrated that MRDD52H and MRDD52H/E55G conferred only marginal resistance to MC in E. coli. These findings suggest that MRD has descended from a previously unidentified quinone reductase, and mutations at the active site of MRD have greatly attenuated its catalytic activity while preserving substrate-binding capability. This presumed evolutionary process might have switched MRD from a potential drug-activating enzyme into the drug-binding component of the MC export system. PMID:11158572

  14. Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites.

    PubMed

    Manzanares, José A; Rimpelä, Anna-Kaisa; Urtti, Arto

    2016-04-04

    Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters.

  15. Impaired financial abilities in Parkinson's disease patients with mild cognitive impairment and dementia.

    PubMed

    Martin, Roy C; Triebel, Kristen L; Kennedy, Richard E; Nicholas, Anthony P; Watts, Ray L; Stover, Natividad P; Brandon, Mariko; Marson, Daniel C

    2013-11-01

    Financial capacity (FC) is an instrumental activity of daily living (IADL) critical to independent functioning and sensitive to cognitive impairment in dementia. Little is known about FC in cognitively impaired patients with Parkinson's disease (PD). The present study investigated FC in PD patients with prodromal and clinical dementia. Participants were 20 older controls and 35 PD patients who met consensus criteria for either mild cognitive impairment (PD-MCI, n = 18) or PD dementia (PDD, n = 17). FC was assessed using a standardized performance based measure consisting of 9 domain and two global scores (Financial Capacity Instrument; FCI) (1). FCI domain and global performance scores were compared across groups. Capacity impairment ratings (no impairment, mild/moderate impairment, severe impairment) were calculated for each PD patient's domain and global scores. Relative to controls, PD-MCI patients were impaired on both FCI global scores and domains of basic monetary skills, financial concepts, and investment decision-making. Relative to both controls and PD-MCI patients, PDD patients were impaired on virtually all FCI variables. With respect to impairment ratings, greater than 50% of PD-MCI patients and greater than 90% of PDD patients were classified as either mild/moderate or severely impaired on the two FCI global scores. Impairment of financial capacity is already present in PD-MCI and is advanced in PDD. Complex cognitively-mediated IADLs such as financial capacity appear to be impaired early in the course of PD dementia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or... impairment(s), even those that are not severe, in determining your residual functional capacity. Pain...

  17. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or... impairment(s), even those that are not severe, in determining your residual functional capacity. Pain...

  18. Multi-drug resistance profile of PR20 HIV-1 protease is attributed to distorted conformational and drug binding landscape: molecular dynamics insights.

    PubMed

    Chetty, Sarentha; Bhakat, Soumendranath; Martin, Alberto J M; Soliman, Mahmoud E S

    2016-01-01

    The PR20 HIV-1 protease, a variant with 20 mutations, exhibits high levels of multi-drug resistance; however, to date, there has been no report detailing the impact of these 20 mutations on the conformational and drug binding landscape at a molecular level. In this report, we demonstrate the first account of a comprehensive study designed to elaborate on the impact of these mutations on the dynamic features as well as drug binding and resistance profile, using extensive molecular dynamics analyses. Comparative MD simulations for the wild-type and PR20 HIV proteases, starting from bound and unbound conformations in each case, were performed. Results showed that the apo conformation of the PR20 variant of the HIV protease displayed a tendency to remain in the open conformation for a longer period of time when compared to the wild type. This led to a phenomena in which the inhibitor seated at the active site of PR20 tends to diffuse away from the binding site leading to a significant change in inhibitor-protein association. Calculating the per-residue fluctuation (RMSF) and radius of gyration, further validated these findings. MM/GBSA showed that the occurrence of 20 mutations led to a drop in the calculated binding free energies (ΔGbind) by ~25.17 kcal/mol and ~5 kcal/mol for p2-NC, a natural peptide substrate, and darunavir, respectively, when compared to wild type. Furthermore, the residue interaction network showed a diminished inter-residue hydrogen bond network and changes in inter-residue connections as a result of these mutations. The increased conformational flexibility in PR20 as a result of loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces led to a loss of protease grip on ligand. It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by

  19. Global alteration of the drug-binding pocket of human P-glycoprotein (ABCB1) by substitution of fifteen conserved residues reveals a negative correlation between substrate size and transport efficiency.

    PubMed

    Vahedi, Shahrooz; Chufan, Eduardo E; Ambudkar, Suresh V

    2017-11-01

    P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport function of P-gp. By employing computational analysis, 15 conserved residues in the drug-binding pocket of human P-gp that interact with substrates were identified and then substituted with tyrosine, including 11 phenylalanine (F72, F303, F314, F336, F732, F759, F770, F938, F942, F983, F994), two leucine (L339, L975), one isoleucine (I306), and one methionine (M949). Characterization of the tyrosine-rich P-gp mutant in HeLa cells demonstrated that this major alteration in the drug-binding pocket by introducing fifteen additional tyrosine residues is well tolerated and has no measurable effect on total or cell surface expression of this mutant. Although the tyrosine-enriched mutant P-gp could transport small to moderate size (<1000 Daltons) fluorescent substrates, its ability to transport large (>1000 Daltons) substrates such as NBD-cyclosporine A, Bodipy-paclitaxel and Bodipy-vinblastine was significantly decreased. This was further supported by the physico-chemical characterization of seventeen tested substrates, which revealed a negative correlation between drug transport and molecular size for the tyrosine-enriched P-gp mutant. Published by Elsevier Inc.

  20. Premelting base pair opening probability and drug binding constant of a daunomycin-poly d(GCAT).poly d(ATGC) complex.

    PubMed Central

    Chen, Y Z; Prohofsky, E W

    1994-01-01

    We calculate room temperature thermal fluctuational base pair opening probability of a daunomycin-poly d(GCAT).poly d(ATGC) complex. This system is constructed at an atomic level of detail based on x-ray analysis of a crystal structure. The base pair opening probabilities are calculated from a modified self-consistent phonon approach of anharmonic lattice dynamics theory. We find that daunomycin binding substantially enhances the thermal stability of one of the base pairs adjacent the drug because of strong hydrogen bonding between the drug and the base. The possible effect of this enhanced stability on the drug inhibition of DNA transcription and replication is discussed. We also calculate the probability of drug dissociation from the helix based on the selfconsistent calculation of the probability of the disruption of drug-base H-bonds and the unstacking probability of the drug. The calculations can be used to determine the equilibrium drug binding constant which is found to be in good agreement with observations on similar daunomycin-DNA systems. PMID:8011914

  1. Enhancing climate Adaptation Capacity for Drinking Water ...

    EPA Pesticide Factsheets

    Journal article This paper considers the adaptation capacity of conventional water treatment systems. A modeling framework is used to illustrate climate adaptation mechanisms that could enable conventional treatment systems to accommodate water quality impairments.

  2. Enhancing climate Adaptation Capacity for Drinking Water ...

    EPA Pesticide Factsheets

    Journal article This paper considers the adaptation capacity of conventional water treatment systems. A modeling framework is used to illustrate climate adaptation mechanisms that could enable conventional treatment systems to accommodate water quality impairments.

  3. [Assessment of legal capacity and testamentary capacity].

    PubMed

    Dreßing, H; Foerster, K; Leygraf, J; Schneider, F

    2014-11-01

    The assessment of legal capacity and testamentary capacity require thorough knowledge of the legal framework and the relevant case law. This paper explains the concept of the legal capacity to contract and the concept of testamentary capacity with respect to German civil law. The relevance of major mental disorders for the assessment of legal capacity and testamentary capacity is discussed.

  4. Atomic modelling and systematic mutagenesis identify residues in multiple drug binding sites that are essential for drug resistance in the major Candida transporter Cdr1.

    PubMed

    Nim, Shweta; Lobato, Lucia Gonzalez; Moreno, Alexis; Chaptal, Vincent; Rawal, Manpreet Kaur; Falson, Pierre; Prasad, Rajendra

    2016-11-01

    The ABC (ATP-Binding Cassette) transporter Cdr1 (Candida drug resistance 1) protein (Cdr1p) of Candida albicans, shows promiscuity towards the substrate it exports and plays a major role in antifungal resistance. It has two transmembrane domains (TMDs) comprising of six transmembrane helices (TMH) that envisage and confer the substrate specificity and two nucleotide binding domains (NBDs), interconnected by extracellular loops (ECLs) and intracellular loops (ICLs) Cdr1p. This study explores the diverse substrate specificity spectrum to get a deeper insight into the structural and functional features of Cdr1p. By screening with the variety of compounds towards an in-house TMH 252 mutant library of Cdr1p, we establish new substrates of Cdr1p. The localization of substrate-susceptible mutants in an ABCG5/G8 homology model highlights the common and specific binding pockets inside the membrane domain, where rhodamines and tetrazoliums mainly engage the N-moiety of Cdr1p, binding between TMH 2, 11 and surrounded by TMH 1, 5. Whereas, tin chlorides involve both N and C moieties located at the interface of TMH 2, 11, 1 and 5. Further, screening of the in house TMH mutant library of Cdr1p displays the TMH12 interaction with tetrazolium chloride, trimethyltin chloride and a Ca(2+) ionophore, A23187. In silico localization reveals a binding site at the TMH 12, 9 and 10 interface, which is widely exposed to the lipid interface. Together, for the first time, our study shows the molecular localization of Cdr1p substrates-binding sites and demonstrates the participation of TMH12 in a peripheral drug binding site.

  5. Mental capacity.

    PubMed

    Williams, Ruth

    2010-02-03

    Three short videos exploring some of the different principles in the Mental Capacity Act 2009 are available on Social Care TV, an online channel intended mainly for the social care sector, although the films are relevant to any professionals whose work is affected by the act. The dramas, which are set in a residential home, a person's own home and a residential school for young people with learning difficulties, concern thedecision-making process and can be viewed at www.scie.org.uk/socialcaretv/topic.asp?guid=377dbe1b-de0c-4d66-bb87-22a243542db2.

  6. Taste - impaired

    MedlinePlus

    ... longer. Causes of impaired taste include: Bell's palsy Common cold Flu and other viral infections Nasal infection, nasal ... your diet. For taste problems due to the common cold or flu, normal taste should return when the ...

  7. Impaired Driving

    MedlinePlus

    Impaired driving is dangerous. It's the cause of more than half of all car crashes. It means operating a ... texting Having a medical condition which affects your driving For your safety and the safety of others, ...

  8. Impaired Driving

    MedlinePlus

    ... people were killed in alcohol-impaired driving crashes, accounting for nearly one-third (31%) of all traffic- ... promotion efforts into practice that influence economic, organizational, policy, and school/community action. 13,14 Using community- ...

  9. Measures of Financial Capacity: A Review.

    PubMed

    Ghesquiere, Angela R; McAfee, Caitlin; Burnett, Jason

    2017-05-23

    Capacity to manage finances and make financial decisions can affect risk for financial exploitation and is often the basis for legal determinations of conservatorship/guardianship. Several structured assessments of financial capacity have been developed, but have not been compared regarding their focus, validity, or reliability. Therefore, we conducted a review of financial capacity measures to examine these factors. We searched electronic databases, reference lists in identified articles, conference proceedings and other grey literature for measures of financial capacity. We then extracted data on the length and domains of each measure, the population for which they were intended, and their validity and reliability. We identified 10 structured measures of financial capacity. Most measures could be completed in 25-30 min, and were designed to be administered to older adults with some level of cognitive impairment. Reliability and validity were high for most. Measurement of financial capacity is complex and multidimensional. When selecting a measure of financial capacity, consideration should be made of the population of focus and the domains of capacity to be assessed. More work is needed on the cultural sensitivity of financial capacity measures, their acceptability, and their use in clinical work. Better understanding of when, and to whom, to administer different financial capacity measures could enhance the ability to accurately detect those suffering from impaired financial capacity, and prevent related negative outcomes like financial exploitation.

  10. Physical Impairment

    NASA Astrophysics Data System (ADS)

    Trewin, Shari

    Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

  11. Preferences for care towards the end of life when decision-making capacity may be impaired: A large scale cross-sectional survey of public attitudes in Great Britain and the United States.

    PubMed

    Clarke, Gemma; Fistein, Elizabeth; Holland, Anthony; Barclay, Matthew; Theimann, Pia; Barclay, Stephen

    2017-01-01

    There is continuing public debate about treatment preferences at the end of life, and the acceptability and legal status of treatments that sustain or end life. However, most surveys use binary yes/no measures, and little is known about preferences in neurological disease when decision-making capacity is lost, as most studies focus on cancer. This study investigates changes in public preferences for care towards the end of life, with a focus on measures to sustain or end life. Large-scale international public opinion surveys using a six-stage patient vignette, respondents chose a level of intervention for each stage as health and decision-making capacity deteriorated. Cross-sectional representative samples of the general public in Great Britain and the USA (N = 2016). Primary outcome measure: changes in respondents' preferences for care, measured on a four-point scale designed before data collection. The scale ranged from: maintaining life at all costs; to intervention with agreement; to no intervention; to measures for ending life. There were no significant differences between GB and USA. Preference for measures to sustain life at all costs peaked at short-term memory loss (30.2%, n = 610). Respondents selecting 'measures to help me die peacefully' increased from 3.9% to 37.0% as the condition deteriorated, with the largest increase occurring when decision-making capacity was lost (10.3% to 23.0%). Predictors of choosing 'measures to help me die peacefully' at any stage were: previous personal experience (OR = 1.34, p<0.010), and older age (OR = 1.09 per decade, p<0.010). Negative predictors: living with children (OR = 0.72, p<0.010) and being of "black" race/ethnicity (OR = 0.45, p<0.001). Public opinion was uniform between GB and USA, but markedly heterogeneous. Despite contemporaneous capacitous consent providing an essential legal safeguard in most jurisdictions, there was a high prevalence of preference for "measures to end my life peacefully" when decision

  12. Preferences for care towards the end of life when decision-making capacity may be impaired: A large scale cross-sectional survey of public attitudes in Great Britain and the United States

    PubMed Central

    Clarke, Gemma; Fistein, Elizabeth; Holland, Anthony; Barclay, Matthew; Theimann, Pia; Barclay, Stephen

    2017-01-01

    Background There is continuing public debate about treatment preferences at the end of life, and the acceptability and legal status of treatments that sustain or end life. However, most surveys use binary yes/no measures, and little is known about preferences in neurological disease when decision-making capacity is lost, as most studies focus on cancer. This study investigates changes in public preferences for care towards the end of life, with a focus on measures to sustain or end life. Methods Large-scale international public opinion surveys using a six-stage patient vignette, respondents chose a level of intervention for each stage as health and decision-making capacity deteriorated. Cross-sectional representative samples of the general public in Great Britain and the USA (N = 2016). Primary outcome measure: changes in respondents’ preferences for care, measured on a four-point scale designed before data collection. The scale ranged from: maintaining life at all costs; to intervention with agreement; to no intervention; to measures for ending life. Results There were no significant differences between GB and USA. Preference for measures to sustain life at all costs peaked at short-term memory loss (30.2%, n = 610). Respondents selecting ‘measures to help me die peacefully’ increased from 3.9% to 37.0% as the condition deteriorated, with the largest increase occurring when decision-making capacity was lost (10.3% to 23.0%). Predictors of choosing ‘measures to help me die peacefully’ at any stage were: previous personal experience (OR = 1.34, p<0.010), and older age (OR = 1.09 per decade, p<0.010). Negative predictors: living with children (OR = 0.72, p<0.010) and being of “black” race/ethnicity (OR = 0.45, p<0.001). Conclusions Public opinion was uniform between GB and USA, but markedly heterogeneous. Despite contemporaneous capacitous consent providing an essential legal safeguard in most jurisdictions, there was a high prevalence of preference for

  13. Attenuated natural killer (NK) cell activation through C-type lectin-like receptor NKp80 is due to an anomalous hemi-immunoreceptor tyrosine-based activation motif (HemITAM) with impaired Syk kinase recruitment capacity.

    PubMed

    Rückrich, Thomas; Steinle, Alexander

    2013-06-14

    Cellular cytotoxicity is the hallmark of NK cells mediating both elimination of virus-infected or malignant cells, and modulation of immune responses. NK cytotoxicity is triggered upon ligation of various activating NK cell receptors. Among these is the C-type lectin-like receptor NKp80 which is encoded in the human Natural Killer Gene Complex (NKC) adjacent to its ligand, activation-induced C-type lectin (AICL). NKp80-AICL interaction promotes cytolysis of malignant myeloid cells, but also stimulates the mutual crosstalk between NK cells and monocytes. While many activating NK cell receptors pair with ITAM-bearing adaptors, we recently reported that NKp80 signals via a hemITAM-like sequence in its cytoplasmic domain. Here we molecularly dissect the NKp80 hemITAM and demonstrate that two non-consensus amino acids, in particular arginine 6, critically impair both hemITAM phosphorylation and Syk recruitment. Impaired Syk recruitment results in a substantial attenuation of cytotoxic responses upon NKp80 ligation. Reconstituting the hemITAM consensus or Syk overexpression resulted in robust NKp80-mediated responsiveness. Collectively, our data provide a molecular rationale for the restrained activation potential of NKp80 and illustrate how subtle alterations in signaling motifs determine subsequent cellular responses. They also suggest that non-consensus alterations in the NKp80 hemITAM, as commonly present among mammalian NKp80 sequences, may have evolved to dampen NKp80-mediated cytotoxic responses toward AICL-expressing cells.

  14. Hearing Impairment

    MedlinePlus

    ... may include inserting an object such as a cotton swab too far into the ear, a sudden explosion or other loud noise, a sudden change in air pressure, a head injury, or repeated ear infections. Sensorineural hearing impairment results from problems with or damage ...

  15. The BRCA1 alternative splicing variant Δ14-15 with an in-frame deletion of part of the regulatory serine-containing domain (SCD) impairs the DNA repair capacity in MCF-7 cells.

    PubMed

    Sevcik, Jan; Falk, Martin; Kleiblova, Petra; Lhota, Filip; Stefancikova, Lenka; Janatova, Marketa; Weiterova, Lenka; Lukasova, Emilie; Kozubek, Stanislav; Pohlreich, Petr; Kleibl, Zdenek

    2012-05-01

    The BRCA1 gene codes for a protein involved in the DNA double strand break (DDSB) repair. Alongside the dominant full-length splicing form of BRCA1, numerous endogenously expressed alternative splicing variants of unknown significance have been described in various tissues. Some of them retain the original BRCA1 reading frame but lack several critical BRCA1 structural domains, suggesting an altered function of the resulting protein in the BRCA1-regulated processes. To characterize the effect of the BRCA1Δ14-15 splicing variant (with an in-frame deletion affecting the regulatory serine-containing domain) on the DDSB repair, we constructed the MCF-7 clones stably expressing the analyzed variant with/without a shRNA-mediated downregulation of the endogenous full-length wild-type BRCA1 expression. Our results show that the expression of the BRCA1Δ14-15 variant delays the γ-radiation-induced DDSB repair, alters the kinetics of irradiation-induced foci formation/decomposition and reduces the non-homologous end-joining capacity in MCF-7 cells. Therefore, the BRCA1Δ14-15 is not able to functionally replace the full-length wt BRCA1 in the DDSB repair. Our findings indicate that the endogenously expressed BRCA1 alternative splicing variants may negatively influence genome stability and support the growing evidence of the pathological potential of the sequence variants generated by an altered or misregulated alternative splicing in the process of mammary malignant transformation.

  16. Comparative spectroscopic studies on drug binding characteristics and protein surface hydrophobicity of native and modified forms of bovine serum albumin: possible relevance to change in protein structure/function upon non-enzymatic glycation.

    PubMed

    Khodarahmi, Reza; Karimi, Seyyed Arash; Ashrafi Kooshk, Mohammad Reza; Ghadami, Seyyed Abolghasem; Ghobadi, Sirous; Amani, Mojtaba

    2012-04-01

    The interaction between serum albumin (SA) and drugs has provided an interesting ground for understanding of drug effects, especially in drug distribution and drug-drug interaction on SA, in the case of multi-drug therapy. Determination of the impact of various factors on drug-protein interaction is especially important upon significant binding of drug to albumin. In the present study, the interaction of two drugs (furosemide and indomethacin) with native and modified albumins were investigated by using various spectroscopic methods. Fluorescence data indicated that 1:1 binding of drugs to bovine serum albumin (BSA) is associated with quenching of albumin intrinsic fluorescence. The Job's plot also confirmed that drug binds to BSA via mentioned stoichiometry. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between drug and albumin may change upon protein modification. The theoretical analyses also suggested some conformational changes of interacting side chains in subdomain IIA binding site (at the vicinity of W237), which were in good agreement with experimental data. Decrease of protein surface hydrophobicity (PSH) was also observed upon both albumin modification and drug binding.

  17. Comparative spectroscopic studies on drug binding characteristics and protein surface hydrophobicity of native and modified forms of bovine serum albumin: Possible relevance to change in protein structure/function upon non-enzymatic glycation

    NASA Astrophysics Data System (ADS)

    Khodarahmi, Reza; Karimi, Seyyed Arash; Ashrafi Kooshk, Mohammad Reza; Ghadami, Seyyed Abolghasem; Ghobadi, Sirous; Amani, Mojtaba

    2012-04-01

    The interaction between serum albumin (SA) and drugs has provided an interesting ground for understanding of drug effects, especially in drug distribution and drug-drug interaction on SA, in the case of multi-drug therapy. Determination of the impact of various factors on drug-protein interaction is especially important upon significant binding of drug to albumin. In the present study, the interaction of two drugs (furosemide and indomethacin) with native and modified albumins were investigated by using various spectroscopic methods. Fluorescence data indicated that 1:1 binding of drugs to bovine serum albumin (BSA) is associated with quenching of albumin intrinsic fluorescence. The Job's plot also confirmed that drug binds to BSA via mentioned stoichiometry. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between drug and albumin may change upon protein modification. The theoretical analyses also suggested some conformational changes of interacting side chains in subdomain IIA binding site (at the vicinity of W237), which were in good agreement with experimental data. Decrease of protein surface hydrophobicity (PSH) was also observed upon both albumin modification and drug binding.

  18. All Vision Impairment

    MedlinePlus

    ... USAJobs Home > Statistics and Data > All Vision Impairment All Vision Impairment Vision Impairment Defined Vision impairment is ... being blind by the U.S. definition.) The category “All Vision Impairment” includes both low vision and blindness. ...

  19. Deficiency of dietary niacin impaired gill immunity and antioxidant capacity, and changes its tight junction proteins via regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella).

    PubMed

    Li, Shun-Quan; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-08-01

    To investigate the effects of dietary niacin on gill immunity, tight junction proteins, antioxidant system and related signaling molecules mRNA expression, young grass carp (Ctenopharyngodon idella) were fed six diets containing graded levels of niacin (3.95-55.01 mg/kg diet) for 8 weeks. The study indicated that niacin deficiency decreased lysozyme and acid phosphatase activities, and complement 3 content, and caused oxidative damage that might be partly due to the decreased copper, zinc superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and reduced glutathione content in fish gills (P < 0.05). Moreover, the relative mRNA levels of antimicrobial peptides (liver expressed antimicrobial peptide 2 and Hepcidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor β1), tight junction proteins (Occludin, zonula occludens 1, Claudin-15 and -3), signaling molecules (inhibitor of κBα (IκBα), target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1) and NF-E2-related factor 2 (Nrf2)) and antioxidant enzymes were significantly decreased (P < 0.05) in niacin-deficient diet group. Conversely, the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 8, interferon γ2, and interleukin 1β), signaling molecules (nuclear factor kappa B p65, IκB kinase α, IκB kinase β, IκB kinase γ, Kelch-like-ECH-associated protein 1b, myosin light chain kinase and p38 mitogen-activated protein kinase (p38 MAPK) were significantly increased (P < 0.05) in fish gills fed niacin-deficient diet. Interestingly, the varying niacin levels of 3.95-55.01 mg/kg diet had no effect on the mRNA level of Kelch-like-ECH-associated protein 1a, Claudin-c and -12 in fish gills (P > 0.05). In conclusion, niacin deficiency decreased gill immunity, impaired gill antioxidant system, as well as regulated mRNA expression of gill tight junction proteins and related signaling

  20. Ten myths about decision-making capacity.

    PubMed

    Ganzini, Linda; Volicer, Ladislav; Nelson, William A; Fox, Ellen; Derse, Arthur R

    2005-01-01

    As a matter of practical reality, what role patients will play in decisions about their health care is determined by whether their clinicians judge them to have decision-making capacity. Because so much hinges on assessments of capacity, clinicians who work with patients have an ethical obligation to understand this concept. This article, based on a report prepared by the National Ethics Committee (NEC) of the Veterans Health Administration (VHA), seeks to provide clinicians with practical information about decision-making capacity and how it is assessed. A study of clinicians and ethics committee chairs carried out under the auspices of the NEC identified the following 10 common myths clinicians hold about decision-making capacity: (1) decision-making capacity and competency are the same; (2) lack of decision-making capacity can be presumed when patients go against medical advice; (3) there is no need to assess decision-making capacity unless patients go against medical advice; (4) decision-making capacity is an "all or nothing" phenomenon; (5) cognitive impairment equals lack of decision-making capacity; (6) lack of decision-making capacity is a permanent condition; (7) patients who have not been given relevant and consistent information about their treatment lack decision-making capacity; (8) all patients with certain psychiatric disorders lack decision-making capacity; (9) patients who are involuntarily committed lack decision-making capacity; and (10) only mental health experts can assess decision-making capacity. By describing and debunking these common misconceptions, this article attempts to prevent potential errors in the clinical assessment of decision-making capacity, thereby supporting patients' right to make choices about their own health care.

  1. Ten myths about decision-making capacity.

    PubMed

    Ganzini, Linda; Volicer, Ladislav; Nelson, William A; Fox, Ellen; Derse, Arthur R

    2004-01-01

    As a matter of practical reality, what role patients will play in decisions about their health care is determined by whether their clinicians judge them to have decision-making capacity. Because so much hinges on assessments of capacity, clinicians who work with patients have an ethical obligation to understand this concept. This article, based on a report prepared by the National Ethics Committee (NEC) of the Veterans Health Administration (VHA), seeks to provide clinicians with practical information about decision-making capacity and how it is assessed. A study of clinicians and ethics committee chairs carried out under the auspices of the NEC identified the following 10 common myths clinicians hold about decision-making capacity: (1) decision-making capacity and competency are the same; (2) lack of decision-making capacity can be presumed when patients go against medical advice; (3) there is no need to assess decision-making capacity unless patients go against medical advice; (4) decision-making capacity is an "all or nothing" phenomenon; (5) cognitive impairment equals lack of decision-making capacity; (6) lack of decision-making capacity is a permanent condition; (7) patients who have not been given relevant and consistent information about their treatment lack decision-making capacity; (8) all patients with certain psychiatric disorders lack decision-making capacity; (9) patients who are involuntarily committed lack decision-making capacity; and (10) only mental health experts can assess decision-making capacity. By describing and debunking these common misconceptions, this article attempts to prevent potential errors in the clinical assessment of decision-making capacity, thereby supporting patients' right to make choices about their own health care.

  2. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or...), even those that are not severe, in determining your residual functional capacity. Pain or...

  3. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  4. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or...), even those that are not severe, in determining your residual functional capacity. Pain or...

  5. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  6. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  7. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  8. CAPACITY OF PATIENTS WITH BRAIN METASTASES TO MAKE TREATMENT DECISIONS

    PubMed Central

    Triebel, Kristen L.; Gerstenecker, Adam; Meneses, Karen; Fiveash, John B.; Meyers, Christina A.; Cutter, Gary; Marson, Daniel C.; Martin, Roy C.; Eakin, Amanda; Watts, Olivia; Nabors, Louis B.

    2015-01-01

    OBJECTIVE To investigate medical decision-making capacity (MDC) in patients with brain metastasis. METHODS Participants were 41 adults with brain metastases with Karnofsky Performance Status scores ≥70 were recruited from an academic medical center and 41 demographically-matched controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument (CCTI) and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant with brain metastasis using cutoff scores derived statistically from the performance of the control group. RESULTS The brain metastases patient group performed significantly below controls on consent standards of understanding and reasoning. Capacity compromise was defined as performance ≤1.5 standard deviations (SD) below the control group mean. Using this definition, approximately 60% of the participants with brain metastases demonstrated capacity compromise on at least one MDC standard. CONCLUSION When defining capacity compromise as performance ≤1.5 SD below the control group mean, over half of patients with brain metastases have reduced capacity to make treatment decisions. This impairment is demonstrated shortly after initial diagnosis of brain metastases and highlights the importance of routine clinical assessment of MDC following diagnosis of brain metastasis. These results also indicate a need for the development and investigation of interventions to support or improve MDC in this patient population. PMID:25613039

  9. Cortical Visual Impairment

    MedlinePlus

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Cortical Visual Impairment En Español Read in Chinese What is cortical visual impairment? Cortical visual impairment (CVI) is a decreased ...

  10. Criterion 2: Maintenance of productive capacity of forest ecosystems

    Treesearch

    Stephen R. Shifley; Francisco X. Aguilar; Nianfu Song; Susan I. Stewart; David J. Nowak; Dale D. Gormanson; W. Keith Moser; Sherri Wormstead; Eric J. Greenfield

    2012-01-01

    People rely on forests, directly and indirectly, for a wide range of goods and services. Measures of forest productive capacity are indicators of the ability of forests to sustainably supply goods and services over time. An ongoing emphasis on maintaining productive capacity of forests can help ensure that utilization of forest resources does not impair long term...

  11. Financial capacity in older adults: a growing concern for clinicians.

    PubMed

    Gardiner, Paul A; Byrne, Gerard J; Mitchell, Leander K; Pachana, Nancy A

    2015-02-02

    Older people with cognitive impairment and/or dementia may be particularly vulnerable to diminished financial decision-making capacity. Financial capacity refers to the ability to satisfactorily manage one's financial affairs in a manner consistent with personal self-interest and values. Impairment of financial capacity makes the older individual vulnerable to financial exploitation, may negatively affect their family's financial situation and places strain on relationships within the family. Clinicians are often on the front line of responding to queries regarding decision-making capacity, and clinical evaluation options are often not well understood. Assessment of financial capacity should include formal objective assessment in addition to a clinical interview and gathering contextual data. Development of a flexible, empirically supported and clinically relevant assessment approach that spans all dimensions of financial capacity yet is simple enough to be used by non-specialist clinicians is needed.

  12. Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity.

    PubMed

    Breslin, Loretta; Prosser, Suzanna L; Cuffe, Sandra; Morrison, Ciaran G

    2014-01-01

    Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog. Primary cilium formation is facilitated by cellular quiescence a temporary cell cycle exit, but the impact of senescence on cilia is unknown. We found that senescent human fibroblasts have increased frequency and length of primary cilia. Levels of the negative ciliary regulator CP110 were reduced in senescent cells, as were levels of key elements of the Hedgehog pathway. Hedgehog inhibition reduced proliferation in young cells with increased cilium length accompanying cell cycle arrest suggesting a regulatory function for Hedgehog in primary ciliation. Depletion of CP110 in young cell populations increased ciliation frequencies and reduced cell proliferation. These data suggest that primary cilia are potentially novel determinants of the reduced cellular proliferation that initiates senescence.

  13. Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity

    PubMed Central

    Breslin, Loretta; Prosser, Suzanna L; Cuffe, Sandra; Morrison, Ciaran G

    2014-01-01

    Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog. Primary cilium formation is facilitated by cellular quiescence a temporary cell cycle exit, but the impact of senescence on cilia is unknown. We found that senescent human fibroblasts have increased frequency and length of primary cilia. Levels of the negative ciliary regulator CP110 were reduced in senescent cells, as were levels of key elements of the Hedgehog pathway. Hedgehog inhibition reduced proliferation in young cells with increased cilium length accompanying cell cycle arrest suggesting a regulatory function for Hedgehog in primary ciliation. Depletion of CP110 in young cell populations increased ciliation frequencies and reduced cell proliferation. These data suggest that primary cilia are potentially novel determinants of the reduced cellular proliferation that initiates senescence. PMID:25486364

  14. Programming placental nutrient transport capacity

    PubMed Central

    Fowden, A L; Ward, J W; Wooding, F P B; Forhead, A J; Constancia, M

    2006-01-01

    Many animal studies and human epidemiological findings have shown that impaired growth in utero is associated with physiological abnormalities in later life and have linked this to tissue programming during suboptimal intrauterine conditions at critical periods of development. However, few of these studies have considered the contribution of the placenta to the ensuing adult phenotype. In mammals, the major determinant of intrauterine growth is the placental nutrient supply, which, in turn, depends on the size, morphology, blood supply and transporter abundance of the placenta and on synthesis and metabolism of nutrients and hormones by the uteroplacental tissues. This review examines the regulation of placental nutrient transfer capacity and the potential programming effects of nutrition and glucocorticoid over-exposure on placental phenotype with particular emphasis on the role of the Igf2 gene in these processes. PMID:16439433

  15. Single 23S rRNA mutations at the ribosomal peptidyl transferase centre confer resistance to valnemulin and other antibiotics in Mycobacterium smegmatis by perturbation of the drug binding pocket.

    PubMed

    Long, Katherine S; Poehlsgaard, Jacob; Hansen, Lykke H; Hobbie, Sven N; Böttger, Erik C; Vester, Birte

    2009-03-01

    Tiamulin and valnemulin target the peptidyl transferase centre (PTC) on the bacterial ribosome. They are used in veterinary medicine to treat infections caused by a variety of bacterial pathogens, including the intestinal spirochetes Brachyspira spp. Mutations in ribosomal protein L3 and 23S rRNA have previously been associated with tiamulin resistance in Brachyspira spp. isolates, but as multiple mutations were isolated together, the roles of the individual mutations are unclear. In this work, individual 23S rRNA mutations associated with pleuromutilin resistance at positions 2055, 2447, 2504 and 2572 (Escherichia coli numbering) are introduced into a Mycobacterium smegmatis strain with a single rRNA operon. The single mutations each confer a significant and similar degree of valnemulin resistance and those at 2447 and 2504 also confer cross-resistance to other antibiotics that bind to the PTC in M. smegmatis. Antibiotic footprinting experiments on mutant ribosomes show that the introduced mutations cause structural perturbations at the PTC and reduced binding of pleuromutilin antibiotics. This work underscores the fact that mutations at nucleotides distant from the pleuromutilin binding site can confer the same level of valnemulin resistance as those at nucleotides abutting the bound drug, and suggests that the former function indirectly by altering local structure and flexibility at the drug binding pocket.

  16. Visual impairment in the hearing impaired students.

    PubMed

    Gogate, Parikshit; Rishikeshi, Nikhil; Mehata, Reshma; Ranade, Satish; Kharat, Jitesh; Deshpande, Madan

    2009-01-01

    Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. To detect and treat visual impairment, if any, in hearing-impaired children. Observational, clinical case series of hearing-impaired children in schools providing special education. Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen's E charts. Refractive errors and squint were treated as per standard practice. Excel software was used for data entry and SSPS for analysis. The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24%) had ocular problems. Refractive errors were the most common morbidity 167(18.5%), but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3%) children, and retinal pigmentary dystrophy in five (0.6%) children. Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense.

  17. On Gaussian feedback capacity

    NASA Technical Reports Server (NTRS)

    Dembo, Amir

    1989-01-01

    Pinsker and Ebert (1970) proved that in channels with additive Gaussian noise, feedback at most doubles the capacity. Cover and Pombra (1989) proved that feedback at most adds half a bit per transmission. Following their approach, the author proves that in the limit as signal power approaches either zero (very low SNR) or infinity (very high SNR), feedback does not increase the finite block-length capacity (which for nonstationary Gaussian channels replaces the standard notion of capacity that may not exist). Tighter upper bounds on the capacity are obtained in the process. Specializing these results to stationary channels, the author recovers some of the bounds recently obtained by Ozarow.

  18. On Gaussian feedback capacity

    NASA Technical Reports Server (NTRS)

    Dembo, Amir

    1989-01-01

    Pinsker and Ebert (1970) proved that in channels with additive Gaussian noise, feedback at most doubles the capacity. Cover and Pombra (1989) proved that feedback at most adds half a bit per transmission. Following their approach, the author proves that in the limit as signal power approaches either zero (very low SNR) or infinity (very high SNR), feedback does not increase the finite block-length capacity (which for nonstationary Gaussian channels replaces the standard notion of capacity that may not exist). Tighter upper bounds on the capacity are obtained in the process. Specializing these results to stationary channels, the author recovers some of the bounds recently obtained by Ozarow.

  19. Cognitive Impairments in Alcohol-Dependent Subjects

    PubMed Central

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-01-01

    Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units. PMID:25076914

  20. Heat Capacity Analysis Report

    SciTech Connect

    A. Findikakis

    2004-11-01

    The purpose of this report is to provide heat capacity values for the host and surrounding rock layers for the waste repository at Yucca Mountain. The heat capacity representations provided by this analysis are used in unsaturated zone (UZ) flow, transport, and coupled processes numerical modeling activities, and in thermal analyses as part of the design of the repository to support the license application. Among the reports that use the heat capacity values estimated in this report are the ''Multiscale Thermohydrologic Model'' report, the ''Drift Degradation Analysis'' report, the ''Ventilation Model and Analysis Report, the Igneous Intrusion Impacts on Waste Packages and Waste Forms'' report, the ''Dike/Drift Interactions report, the Drift-Scale Coupled Processes (DST and TH Seepage) Models'' report, and the ''In-Drift Natural Convection and Condensation'' report. The specific objective of this study is to determine the rock-grain and rock-mass heat capacities for the geologic stratigraphy identified in the ''Mineralogic Model (MM3.0) Report'' (BSC 2004 [DIRS 170031], Table 1-1). This report provides estimates of the heat capacity for all stratigraphic layers except the Paleozoic, for which the mineralogic abundance data required to estimate the heat capacity are not available. The temperature range of interest in this analysis is 25 C to 325 C. This interval is broken into three separate temperature sub-intervals: 25 C to 95 C, 95 C to 114 C, and 114 C to 325 C, which correspond to the preboiling, trans-boiling, and postboiling regimes. Heat capacity is defined as the amount of energy required to raise the temperature of a unit mass of material by one degree (Nimick and Connolly 1991 [DIRS 100690], p. 5). The rock-grain heat capacity is defined as the heat capacity of the rock solids (minerals), and does not include the effect of water that exists in the rock pores. By comparison, the rock-mass heat capacity considers the heat capacity of both solids and pore

  1. Impaired Waters and TMDLs

    EPA Pesticide Factsheets

    The 303(d) program provides guidance and technical resources to assist States in submitting lists of impaired waterbodies and the development of Total Maximum Daily Loads of the pollutant causing the impairment.

  2. Impaired Driving - Multiple Languages

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Impaired Driving URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Impaired Driving - Multiple Languages To use the sharing features on ...

  3. Liquid heat capacity lasers

    DOEpatents

    Comaskey, Brian J.; Scheibner, Karl F.; Ault, Earl R.

    2007-05-01

    The heat capacity laser concept is extended to systems in which the heat capacity lasing media is a liquid. The laser active liquid is circulated from a reservoir (where the bulk of the media and hence waste heat resides) through a channel so configured for both optical pumping of the media for gain and for light amplification from the resulting gain.

  4. Liquid heat capacity lasers

    DOEpatents

    Comaskey, Brian J.; Scheibner, Karl F.; Ault, Earl R.

    2007-05-01

    The heat capacity laser concept is extended to systems in which the heat capacity lasing media is a liquid. The laser active liquid is circulated from a reservoir (where the bulk of the media and hence waste heat resides) through a channel so configured for both optical pumping of the media for gain and for light amplification from the resulting gain.

  5. Problems of Excess Capacity

    NASA Technical Reports Server (NTRS)

    Douglas, G.

    1972-01-01

    The problems of excess capacity in the airline industry are discussed with focus on the following topics: load factors; fair rate of return on investment; service-quality rivalry among airlines; pricing (fare) policies; aircraft production; and the impacts of excess capacity on operating costs. Also included is a discussion of the interrelationships among these topics.

  6. Nanofluid heat capacities

    NASA Astrophysics Data System (ADS)

    Starace, Anne K.; Gomez, Judith C.; Wang, Jun; Pradhan, Sulolit; Glatzmaier, Greg C.

    2011-12-01

    Significant increases in the heat capacity of heat transfer fluids are needed not only to reduce the costs of liquid heating and cooling processes, but also to bring clean energy producing technologies like concentrating solar power (CSP) to price parity with conventional energy generation. It has been postulated that nanofluids could have higher heat capacities than conventional fluids. In this work, nano- and micron-sized particles were added to five base fluids (poly-α olefin, mineral oil, ethylene glycol, a mixture of water and ethylene glycol, and calcium nitrate tetrahydrate), and the resulting heat capacities were measured and compared with those of the neat base fluids and the weighted average of the heat capacities of the components. The particles used were inert metals and metal oxides that did not undergo any phase transitions over the temperature range studied. In the nanofluids studied here, we found no increase in heat capacity upon the addition of the particles larger than the experimental error.

  7. Finances in the Older Patient with Cognitive Impairment

    PubMed Central

    Widera, Eric; Steenpass, Veronika; Marson, Daniel; Sudore, Rebecca

    2013-01-01

    Financial capacity is the ability to manage money and financial assets in ways that meet a person’s needs and which are consistent with his/her values and self-interest. Financial capacity is essential for an individual to function independently in our society; however, dementia eventually leads to a complete loss of financial capacity. Many patients with cognitive impairment and their families turn to their primary care clinician for help with financial impairment, yet most clinicians do not understand their role or how to help. We review the prevalence and impact of financial incapacity in older adults with cognitive impairment. We also articulate the role of the primary clinician which includes: (1) educating older adult patients and families about the need for advance financial planning; (2) recognizing signs of possible impaired financial capacity; (3) assessing financial impairments in cognitively impaired adults; (4) recommending interventions to help patients maintain financial independence; and (5) knowing when and to whom to make medical and legal referrals. Clearly delineating the clinician’s role in financial impairment can lead to the establishment of effective financial protections and can limit the economic, psychological, and legal hardships of financial incapacity on patients with dementia and their families. PMID:21325186

  8. Adapting for Impaired Patrons.

    ERIC Educational Resources Information Center

    Schuyler, Michael

    1999-01-01

    Describes how a library, with an MCI Corporation grant, approached the process of setting up computers for the visually impaired. Discusses preparations, which included hiring a visually-impaired user as a consultant and contacting the VIP (Visually Impaired Persons) group; equipment; problems with the graphical user interface; and training.…

  9. Capacity issues and decision-making in dementia.

    PubMed

    Hegde, Soumya; Ellajosyula, Ratnavalli

    2016-10-01

    Capacity to make one's own decisions is fundamental to the autonomy of the individual. Capacity is a functional assessment made by a clinician to determine if a patient is capable of making a specific decision. Competency is a global assessment and legal determination made by a judge in court. Capacity evaluation for a patient with dementia is used to determine whether the patient is capable of giving informed consent, participate in research, manage their finances, live independently, make a will, and have ability to drive. Patients with dementia cannot be assumed to have impaired capacity. Even a patient with moderate or severe dementia, with obviously impaired capacity may still be able to indicate a choice and show some understanding. Four key components of decision-making in a capacity evaluation include understanding, communicating a choice, appreciation, and reasoning. Assessment of capacity requires a direct interview with the patient using open-ended questions and may include both informal and formal approaches depending on the situation and the context. A baseline cognitive evaluation with a simple test to assess executive function is often useful in capacity evaluation. All capacity evaluations are situation specific, relating to the particular decision under consideration, and are not global in scope. The clinician needs to spend adequate time with the patient and the family allaying their anxieties and also consider the sociocultural context. The area of capacity has considerable overlap with law and the clinician treating patients with dementia should understand the complexities of assessment and the implications of impaired capacity. It is also essential that the clinician be well informed and keep meticulous records. It is crucial to strike a balance between respecting the patient autonomy and acting in his/her best interest.

  10. Capacity issues and decision-making in dementia

    PubMed Central

    Hegde, Soumya; Ellajosyula, Ratnavalli

    2016-01-01

    Capacity to make one's own decisions is fundamental to the autonomy of the individual. Capacity is a functional assessment made by a clinician to determine if a patient is capable of making a specific decision. Competency is a global assessment and legal determination made by a judge in court. Capacity evaluation for a patient with dementia is used to determine whether the patient is capable of giving informed consent, participate in research, manage their finances, live independently, make a will, and have ability to drive. Patients with dementia cannot be assumed to have impaired capacity. Even a patient with moderate or severe dementia, with obviously impaired capacity may still be able to indicate a choice and show some understanding. Four key components of decision-making in a capacity evaluation include understanding, communicating a choice, appreciation, and reasoning. Assessment of capacity requires a direct interview with the patient using open-ended questions and may include both informal and formal approaches depending on the situation and the context. A baseline cognitive evaluation with a simple test to assess executive function is often useful in capacity evaluation. All capacity evaluations are situation specific, relating to the particular decision under consideration, and are not global in scope. The clinician needs to spend adequate time with the patient and the family allaying their anxieties and also consider the sociocultural context. The area of capacity has considerable overlap with law and the clinician treating patients with dementia should understand the complexities of assessment and the implications of impaired capacity. It is also essential that the clinician be well informed and keep meticulous records. It is crucial to strike a balance between respecting the patient autonomy and acting in his/her best interest. PMID:27891023

  11. High Visual Working Memory Capacity in Trait Social Anxiety

    PubMed Central

    Moriya, Jun; Sugiura, Yoshinori

    2012-01-01

    Working memory capacity is one of the most important cognitive functions influencing individual traits, such as attentional control, fluid intelligence, and also psychopathological traits. Previous research suggests that anxiety is associated with impaired cognitive function, and studies have shown low verbal working memory capacity in individuals with high trait anxiety. However, the relationship between trait anxiety and visual working memory capacity is still unclear. Considering that people allocate visual attention more widely to detect danger under threat, visual working memory capacity might be higher in anxious people. In the present study, we show that visual working memory capacity increases as trait social anxiety increases by using a change detection task. When the demand to inhibit distractors increased, however, high visual working memory capacity diminished in individuals with social anxiety, and instead, impaired filtering of distractors was predicted by trait social anxiety. State anxiety was not correlated with visual working memory capacity. These results indicate that socially anxious people could potentially hold a large amount of information in working memory. However, because of an impaired cognitive function, they could not inhibit goal-irrelevant distractors and their performance decreased under highly demanding conditions. PMID:22496783

  12. Memory Impairment in Children with Language Impairment

    ERIC Educational Resources Information Center

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  13. Visual impairment in the hearing impaired students

    PubMed Central

    Gogate, Parikshit; Rishikeshi, Nikhil; Mehata, Reshma; Ranade, Satish; Kharat, Jitesh; Deshpande, Madan

    2009-01-01

    Background: Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim: To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design: Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods: Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen's E charts. Refractive errors and squint were treated as per standard practice. Statistical Analysis: Excel software was used for data entry and SSPS for analysis. Results: The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24%) had ocular problems. Refractive errors were the most common morbidity 167(18.5%), but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3%) children, and retinal pigmentary dystrophy in five (0.6%) children. Conclusion: Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense. PMID:19861747

  14. Memory Impairment in Children with Language Impairment

    ERIC Educational Resources Information Center

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  15. Auditory spatial localization: Developmental delay in children with visual impairments.

    PubMed

    Cappagli, Giulia; Gori, Monica

    2016-01-01

    For individuals with visual impairments, auditory spatial localization is one of the most important features to navigate in the environment. Many works suggest that blind adults show similar or even enhanced performance for localization of auditory cues compared to sighted adults (Collignon, Voss, Lassonde, & Lepore, 2009). To date, the investigation of auditory spatial localization in children with visual impairments has provided contrasting results. Here we report, for the first time, that contrary to visually impaired adults, children with low vision or total blindness show a significant impairment in the localization of static sounds. These results suggest that simple auditory spatial tasks are compromised in children, and that this capacity recovers over time.

  16. Refinery Capacity Report

    EIA Publications

    2016-01-01

    Data series include fuel, electricity, and steam purchased for consumption at the refinery; refinery receipts of crude oil by method of transportation; and current and projected atmospheric crude oil distillation, downstream charge, and production capacities. Respondents are operators of all operating and idle petroleum refineries (including new refineries under construction) and refineries shut down during the previous year, located in the 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, Guam, and other U.S. possessions. The Refinery Capacity Report does not contain working and shell storage capacity data. This data is now being collected twice a year as of March 31 and September 30 on the Form EIA-810, "Monthly Refinery Report", and is now released as a separate report Working and Net Available Shell Storage Capacity.

  17. Refinery Capacity Report

    EIA Publications

    2017-01-01

    Data series include fuel, electricity, and steam purchased for consumption at the refinery; refinery receipts of crude oil by method of transportation; and current and projected atmospheric crude oil distillation, downstream charge, and production capacities. Respondents are operators of all operating and idle petroleum refineries (including new refineries under construction) and refineries shut down during the previous year, located in the 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, Guam, and other U.S. possessions. The Refinery Capacity Report does not contain working and shell storage capacity data. This data is now being collected twice a year as of March 31 and September 30 on the Form EIA-810, "Monthly Refinery Report", and is now released as a separate report Working and Net Available Shell Storage Capacity.

  18. Panama Canal capacity analysis

    SciTech Connect

    Bronzini, M.S.

    1995-04-27

    Predicting the transit capacities of the various Panama Canal alternatives required analyzing data on present Canal operations, adapting and extending an existing computer simulation model, performing simulation runs for each of the alternatives, and using the simulation model outputs to develop capacity estimates. These activities are summarized in this paper. A more complete account may be found in the project final report (TAMS 1993). Some of the material in this paper also appeared in a previously published paper (Rosselli, Bronzini, and Weekly 1994).

  19. Capacity to consent to research among patients with bipolar disorder.

    PubMed

    Misra, Sahana; Ganzini, Linda

    2004-06-01

    Experts have debated the influence of mental illness on decision-making capacity. This paper reviews concepts of decision-making capacity and existing research on the influence of mental illness on capacity to consent to research. We propose how bipolar disorder, especially mania, may have an effect on consent capacity. The current conceptualization of capacity utilizes legal standards of 'choice', 'understanding', 'appreciation' and 'rational reasoning', as well as voluntarism, or the assurance that the patient is free to agree or to decline to participate in research. Studies of patients with schizophrenia suggest impaired cognition influences 'understanding' and is more important than severity of psychosis in affecting decision-making abilities. There are no studies of sources and extent of impairment to consent to research among manic patients. Mania may influence a patient's understanding of the research protocol, but also alter the patient's views, values and level of insight, thus impairing decision-making abilities at the 'appreciation' standard even when the patient understands the relevant information. Mania may impact freedom to decide, yet paradoxically, manic patients may be less influenced by others and less vulnerable to coercion, undue influence and undue incentives compared to patients without mental illness. We suggest that in patients with mood disorders, the legal standard of appreciation be thoroughly probed during the consent procedure. Studies of the effect of mania and depression on consent capacity and voluntarism are needed in order to develop processes that increase safeguards in the informed consent process.

  20. Uncertainty in adaptive capacity

    NASA Astrophysics Data System (ADS)

    Adger, W. Neil; Vincent, Katharine

    2005-03-01

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. To cite this article: W.N. Adger, K. Vincent, C. R. Geoscience 337 (2005).

  1. Capacity Maximizing Constellations

    NASA Technical Reports Server (NTRS)

    Barsoum, Maged; Jones, Christopher

    2010-01-01

    Some non-traditional signal constellations have been proposed for transmission of data over the Additive White Gaussian Noise (AWGN) channel using such channel-capacity-approaching codes as low-density parity-check (LDPC) or turbo codes. Computational simulations have shown performance gains of more than 1 dB over traditional constellations. These gains could be translated to bandwidth- efficient communications, variously, over longer distances, using less power, or using smaller antennas. The proposed constellations have been used in a bit-interleaved coded modulation system employing state-ofthe-art LDPC codes. In computational simulations, these constellations were shown to afford performance gains over traditional constellations as predicted by the gap between the parallel decoding capacity of the constellations and the Gaussian capacity

  2. Geothermal Plant Capacity Factors

    SciTech Connect

    Greg Mines; Jay Nathwani; Christopher Richard; Hillary Hanson; Rachel Wood

    2015-01-01

    The capacity factors recently provided by the Energy Information Administration (EIA) indicated this plant performance metric had declined for geothermal power plants since 2008. Though capacity factor is a term commonly used by geothermal stakeholders to express the ability of a plant to produce power, it is a term frequently misunderstood and in some instances incorrectly used. In this paper we discuss how this capacity factor is defined and utilized by the EIA, including discussion on the information that the EIA requests from operations in their 923 and 860 forms that are submitted both monthly and annually by geothermal operators. A discussion is also provided regarding the entities utilizing the information in the EIA reports, and how those entities can misinterpret the data being supplied by the operators. The intent of the paper is to inform the facility operators as the importance of the accuracy of the data that they provide, and the implications of not providing the correct information.

  3. Dual capacity reciprocating compressor

    DOEpatents

    Wolfe, R.W.

    1984-10-30

    A multi-cylinder compressor particularly useful in connection with northern climate heat pumps and in which different capacities are available in accordance with reversing motor rotation is provided with an eccentric cam on a crank pin under a fraction of the connecting rods, and arranged for rotation upon the crank pin between opposite positions 180[degree] apart so that with cam rotation on the crank pin such that the crank throw is at its normal maximum value all pistons pump at full capacity, and with rotation of the crank shaft in the opposite direction the cam moves to a circumferential position on the crank pin such that the overall crank throw is zero. Pistons whose connecting rods ride on a crank pin without a cam pump their normal rate with either crank rotational direction. Thus a small clearance volume is provided for any piston that moves when in either capacity mode of operation. 6 figs.

  4. Dual capacity reciprocating compressor

    DOEpatents

    Wolfe, Robert W.

    1984-01-01

    A multi-cylinder compressor 10 particularly useful in connection with northern climate heat pumps and in which different capacities are available in accordance with reversing motor 16 rotation is provided with an eccentric cam 38 on a crank pin 34 under a fraction of the connecting rods, and arranged for rotation upon the crank pin between opposite positions 180.degree. apart so that with cam rotation on the crank pin such that the crank throw is at its normal maximum value all pistons pump at full capacity, and with rotation of the crank shaft in the opposite direction the cam moves to a circumferential position on the crank pin such that the overall crank throw is zero. Pistons 24 whose connecting rods 30 ride on a crank pin 36 without a cam pump their normal rate with either crank rotational direction. Thus a small clearance volume is provided for any piston that moves when in either capacity mode of operation.

  5. Panel on Capacity Building

    NASA Astrophysics Data System (ADS)

    Elhadani, D.

    The demonstration was made that space technologies are an important tool for developing countries. But the fundamental question is how those countries could integrate such technologies, in an effective an operational way, in the process of resources management and administration. Capacity building is a cornerstone in any strategy to set up a national programme or infrastructure for the use of space technologies. The proposed presentation attempts to bring the first elements on the actual uses of space technology in developing countries compared to their needs, the role of training activities and programs in the capacity building process as well as the role of international cooperation and what are the required conditions to ensure sustainability of the established capacities.

  6. Type 2 diabetes mellitus and exercise impairment.

    PubMed

    Reusch, Jane E B; Bridenstine, Mark; Regensteiner, Judith G

    2013-03-01

    Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.

  7. The CD11a binding site of efalizumab in psoriatic skin tissue as analyzed by Multi-Epitope Ligand Cartography robot technology. Introduction of a novel biological drug-binding biochip assay.

    PubMed

    Bonnekoh, B; Böckelmann, R; Pommer, A J; Malykh, Y; Philipsen, L; Gollnick, H

    2007-01-01

    -1) as its ligand was most prevalent in the dermal vessels. T lymphocytes (for which the markers were CD3, CD8, CD4, and CD45R0) were the major cellular targets of efalizumab. In contrast, NK cells were only a minor target of efalizumab. Our study demonstrated that efalizumab represents a treatment for psoriasis that primarily targets memory CD4+ and CD8+ T cells and has a high specificity for psoriatic disease activity. Moreover, we hereby introduce the novel principle of a biological drug-binding biochip assay being especially useful for the future monitoring of psoriatic skin lesions under efalizumab treatment conditions. (c) 2007 S. Karger AG, Basel.

  8. Education for the Hearing Impaired (Auditorily Impaired).

    ERIC Educational Resources Information Center

    World Federation of the Deaf, Rome (Italy).

    Education for the hearing impaired is discussed in nine conference papers. J. N. Howarth describes "The Education of Deaf Children in Schools for Hearing Pupils in the United Kingdom" and A.I.Dyachkov of the U.S.S.R. outlines Didactical Principles of Educating the Deaf in the Light of their Rehabilitation Goal." Seven papers from…

  9. Development or Impairment?

    ERIC Educational Resources Information Center

    Hakansson, Gisela

    2010-01-01

    Joanne Paradis' Keynote Article on bilingualism and specific language impairment (SLI) is an impressive overview of research in language acquisition and language impairment. Studying different populations is crucial both for theorizing about language acquisition mechanisms, and for practical purposes of diagnosing and supporting children with…

  10. Development or Impairment?

    ERIC Educational Resources Information Center

    Hakansson, Gisela

    2010-01-01

    Joanne Paradis' Keynote Article on bilingualism and specific language impairment (SLI) is an impressive overview of research in language acquisition and language impairment. Studying different populations is crucial both for theorizing about language acquisition mechanisms, and for practical purposes of diagnosing and supporting children with…

  11. Testamentary capacity and delirium.

    PubMed

    Liptzin, Benjamin; Peisah, Carmelle; Shulman, Kenneth; Finkel, Sanford

    2010-09-01

    With the aging of the population there will be a substantial transfer of wealth in the next 25 years. The presence of delirium can complicate the evaluation of an older person's testamentary capacity and susceptibility to undue influence but has not been well examined in the existing literature. A subcommittee of the IPA Task Force on Testamentary Capacity and Undue Influence undertook to review how to assess prospectively and retrospectively testamentary capacity and susceptibility to undue influence in patients with delirium. The subcommittee identified questions that should be asked in cases where someone changes their will or estate plan towards the end of their life in the presence of delirium. These questions include: was there consistency in the patient's wishes over time? Were these wishes expressed during a "lucid interval" when the person was less confused? Were the patient's wishes clearly expressed in response to open-ended questions? Is there clear documentation of the patient's mental status at the time of the discussion? This review with some case examples provides guidance on how to consider the question of testamentary capacity or susceptibility to undue influence in someone undergoing an episode of delirium.

  12. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  13. Seismic capacity of switchgear

    SciTech Connect

    Bandyopadhyay, K.; Hofmayer, C.; Kassir, M.; Pepper, S.

    1989-01-01

    As part of a component fragility program sponsored by the USNRC, BNL has collected existing information on the seismic capacity of switchgear assemblies from major manufacturers. Existing seismic test data for both low and medium voltage switchgear assemblies have been evaluated and the generic results are presented in this paper. The failure modes are identified and the corresponding generic lower bound capacity levels are established. The test response spectra have been used as a measure of the test vibration input. The results indicate that relays chatter at a very low input level at the base of the switchgear cabinet. This change of state of devices including relays have been observed. Breaker tripping occurs at a higher vibration level. Although the structural failure of internal elements have been noticed, the overall switchgear cabinet structure withstands a high vibration level. 5 refs., 2 figs., 2 tabs.

  14. Impairment in Non-Word Repetition: A Marker for Language Impairment or Reading Impairment?

    ERIC Educational Resources Information Center

    Baird, Gillian; Slonims, Vicky; Simonoff, Emily; Dworzynski, Katharina

    2011-01-01

    Aim: A deficit in non-word repetition (NWR), a measure of short-term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language…

  15. Impairment in Non-Word Repetition: A Marker for Language Impairment or Reading Impairment?

    ERIC Educational Resources Information Center

    Baird, Gillian; Slonims, Vicky; Simonoff, Emily; Dworzynski, Katharina

    2011-01-01

    Aim: A deficit in non-word repetition (NWR), a measure of short-term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language…

  16. Heat Capacity Mapping Mission

    NASA Technical Reports Server (NTRS)

    Nilsson, C. S.; Andrews, J. C.; Scully-Power, P.; Ball, S.; Speechley, G.; Latham, A. R. (Principal Investigator)

    1980-01-01

    The Tasman Front was delineated by airborne expendable bathythermograph survey; and an Heat Capacity Mapping Mission (HCMM) IR image on the same day shows the same principal features as determined from ground-truth. It is clear that digital enhancement of HCMM images is necessary to map ocean surface temperatures and when done, the Tasman Front and other oceanographic features can be mapped by this method, even through considerable scattered cloud cover.

  17. Enhancing capacity management.

    PubMed

    Rees, Susan; Houlahan, Beth; Lavrenz, Dennise

    2014-03-01

    It is essential for organizations to be able to accept patients requiring care. Capacity planning and management are necessary to ensure an organization has an accepting physician/service, an available bed, and staff to care for the patient and family. This organization implemented strategies including communication plans, staffing guidelines, morning rounds, proactive planning, and an escalation process to reverse the trend of not being able to accept all patients.

  18. Community Capacity Building

    PubMed Central

    Goytia, Crispin N.; Todaro-Rivera, Lea; Brenner, Barbara; Shepard, Peggy; Piedras, Veronica; Horowitz, Carol

    2013-01-01

    Background: Successful community–academic research partnerships require building the capacity of both community-based organizations (CBOs) and academics to conduct collaborative research of mutual interest and benefit. Yet, information about the needs and goals of research-interested CBOs is lacking. Our partnership aimed to conduct a community research needs assessment and to use results to develop future capacity-building programs for CBOs. Methods: Based on our review of the literature, informal interviews with research-interested CBOs and community-engaged research groups locally and nationally, we developed a needs assessment survey. Key domains of this survey included history and experience with research collaboration, interest in specific research topics, and preference for learning format and structure. We trained community health workers (CHWs) to recruit senior leaders from CBOs in New York City (NYC) and encourage them to complete an on-line survey. Results: Fully 54% (33/61) of CBOs completed the needs assessment. Most (69%) reported involvement with research or evaluation in the last 2 years and 33% had some funding for research. Although 75% had collaborated with academic institutions in the past, 58% did not rate this experience well. The four areas respondents prioritized for skills building were program evaluation, developing needs assessments, building surveys, and understanding statistical analyses. They were less interested in learning to build collaborations with academics. Conclusions: A formal needs assessment of research training and educational needs of CBOs revealed that most had experience, albeit negative, with academic collaborations. CBO leaders wanted to build skills to conduct and analyze assessments and program evaluations. Our community–academic partnership is using these findings to develop a research capacity-building course. Other partnerships should consider conducting such assessments to transform the capacity of CBOs to

  19. Hearing or speech impairment - resources

    MedlinePlus

    Resources - hearing or speech impairment ... The following organizations are good resources for information on hearing impairment or speech impairment: Alexander Graham Bell Association for the Deaf and Hard of Hearing -- www.agbell. ...

  20. CSTI high capacity power

    SciTech Connect

    Winter, J.M.

    1994-09-01

    The SP-100 program was established in 1983 by DOD, DOE, and NASA as a joint program to develop the technology necessary for space nuclear power systems for military and civil application. During FY86 and 87, the NASA SP-100 Advanced Technology Program was devised to maintain the momentum of promising technology advancement efforts started during Phase I of SP-100 and to strengthen, in key areas, the chances for successful development and growth capability of space nuclear reactor power systems for future space applications. In FY88, the Advanced Technology Program was incorporated into NASA`s new Civil Space Technology Initiative (CSTI). The CSTI Program was established to provide the foundation for technology development in automation and robotics, information, propulsion, and power. The CSTI High Capacity Power Program builds on the technology efforts of the SP-100 program, incorporates the previous NASA SP-100 Advanced Technology project, and provides a bridge to NASA Project Pathfinder. The elements of CSTI High Capacity Power development include Conversion Systems, Thermal Management, Power Management, System Diagnostics, and Environmental Interactions. Technology advancement in all areas, including materials, is required to assure the high reliability and 7 to 10 year lifetime demanded for future space nuclear power systems. The overall program will develop and demonstrate the technology base required to provide a wide range of modular power systems as well as allowing mission independence from solar and orbital attitude requirements. Several recent advancements in CSTI High Capacity power development will be discussed.

  1. CSTI High Capacity Power

    NASA Technical Reports Server (NTRS)

    Winter, Jerry M.

    1989-01-01

    The SP-100 program was established in 1983 by DOD, DOE, and NASA as a joint program to develop the technology necessary for space nuclear power systems for military and civil application. During FY-86 and 87, the NASA SP-100 Advanced Technology Program was devised to maintain the momentum of promising technology advancement efforts started during Phase 1 of SP-100 and to strengthen, in key areas, the chances for successful development and growth capability of space nuclear reactor power systems for future space applications. In FY-88, the Advanced Technology Program was incorporated into NASA's new Civil Space Technology Initiative (CSTI). The CSTI Program was established to provide the foundation for technology development in automation and robotics, information, propulsion, and power. The CSTI High Capacity Power Program builds on the technology efforts of the SP-100 program, incorporates the previous NASA SP-100 Advanced Technology project, and provides a bridge to NASA Project Pathfinder. The elements of CSTI High Capacity Power development include Conversion Systems, Thermal Management, Power Management, System Diagnostics, and Environmental Interactions. Technology advancement in all areas, including materials, is required to assure the high reliability and 7 to 10 year lifetime demanded for future space nuclear power systems. The overall program will develop and demonstrate the technology base required to provide a wide range of modular power systems as well as allowing mission independence from solar and orbital attitude requirements. Several recent advancements in CSTI High Capacity power development will be discussed.

  2. The Nature of Individual Differences in Working Memory Capacity: Active Maintenance in Primary Memory and Controlled Search from Secondary Memory

    ERIC Educational Resources Information Center

    Unsworth, Nash; Engle, Randall W.

    2007-01-01

    Studies examining individual differences in working memory capacity have suggested that individuals with low working memory capacities demonstrate impaired performance on a variety of attention and memory tasks compared with individuals with high working memory capacities. This working memory limitation can be conceived of as arising from 2…

  3. Kids' Quest: Vision Impairment

    MedlinePlus

    ... most important job. Return to Steps World-Wide Web Search Kids Health: What is Vision Impairment What ... for the Blind (AFB) created the Braille Bug web site to teach sighted children about braille, and ...

  4. Speech impairment (adult)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003204.htm Speech impairment (adult) To use the sharing features on ... 2017, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  5. Evaluation of hearing impairment.

    PubMed

    Zadeh, M H; Selesnick, S H

    2001-01-01

    Hearing impairment is among the most common medical condition presenting to health care professionals. Ear anatomy, physiology, and pathology resulting in hearing loss are discussed. A systematic approach to evaluation, diagnosis, and treatment is presented.

  6. Profiling posttraumatic functional impairment.

    PubMed

    Norman, Sonya B; Stein, Murray B; Davidson, Jonathan R T

    2007-01-01

    Many individuals who have been exposed to psychological trauma suffer from impaired functioning, regardless of whether they have PTSD. Our purpose was to identify a subset of PTSD symptoms linked to functional impairment to a) improve the likelihood that individuals with posttraumatic impairment receive treatment, and b) offer a method to assess cost-burden of trauma history in epidemiological studies. We examined patterns of trauma-related symptoms in two independent community surveys (N=1002 and 630). Rank ordering of symptoms and their associations with impairment guided construction of an impairment-related profile in the first data set. The profile was then tested in the second data set. The derived symptom profile, consisting of intense recollections and/or emotional symptoms upon exposure to reminders, plus one or more of numbing/detachment, avoidance, sleep problems, concentration problems, or hypervigilance, detected the majority (88% and 74%) of persons with posttraumatic functional impairment. The symptom profile can help identify traumatized individuals who may benefit from treatment but do not necessarily meet criteria for PTSD.

  7. Exacerbated Vulnerability in Existential Changes: The Essence of Dealing with Reduced Working Capacity

    ERIC Educational Resources Information Center

    Steingrímsdóttir, Sigrún Hulda; Halldórsdóttir, Sigríður

    2016-01-01

    The purpose of this phenomenological study was to explore people's experience of reduced working capacity and their encounters with professionals in that life situation. We collected data through in-depth interviews with eight individuals. The main finding of the current research is how illness and accident impairing work capacity "exacerbate…

  8. Exacerbated Vulnerability in Existential Changes: The Essence of Dealing with Reduced Working Capacity

    ERIC Educational Resources Information Center

    Steingrímsdóttir, Sigrún Hulda; Halldórsdóttir, Sigríður

    2016-01-01

    The purpose of this phenomenological study was to explore people's experience of reduced working capacity and their encounters with professionals in that life situation. We collected data through in-depth interviews with eight individuals. The main finding of the current research is how illness and accident impairing work capacity "exacerbate…

  9. Quantum reading capacity

    NASA Astrophysics Data System (ADS)

    Pirandola, Stefano; Lupo, Cosmo; Giovannetti, Vittorio; Mancini, Stefano; Braunstein, Samuel L.

    2011-11-01

    The readout of a classical memory can be modelled as a problem of quantum channel discrimination, where a decoder retrieves information by distinguishing the different quantum channels encoded in each cell of the memory (Pirandola 2011 Phys. Rev. Lett. 106 090504). In the case of optical memories, such as CDs and DVDs, this discrimination involves lossy bosonic channels and can be remarkably boosted by the use of nonclassical light (quantum reading). Here we generalize these concepts by extending the model of memory from single-cell to multi-cell encoding. In general, information is stored in a block of cells by using a channel-codeword, i.e. a sequence of channels chosen according to a classical code. Correspondingly, the readout of data is realized by a process of ‘parallel’ channel discrimination, where the entire block of cells is probed simultaneously and decoded via an optimal collective measurement. In the limit of a large block we define the quantum reading capacity of the memory, quantifying the maximum number of readable bits per cell. This notion of capacity is nontrivial when we suitably constrain the physical resources of the decoder. For optical memories (encoding bosonic channels), such a constraint is energetic and corresponds to fixing the mean total number of photons per cell. In this case, we are able to prove a separation between the quantum reading capacity and the maximum information rate achievable by classical transmitters, i.e. arbitrary classical mixtures of coherent states. In fact, we can easily construct nonclassical transmitters that are able to outperform any classical transmitter, thus showing that the advantages of quantum reading persist in the optimal multi-cell scenario.

  10. Variable capacity flywheel

    SciTech Connect

    Ban, M.

    1985-06-04

    A variable capacity flywheel comprises a main flywheel coupled with the rotating shaft of an engine and at least one rotatable auxiliary flywheel. Both are selectively engaged and disengaged with one another by means of an electromagnetic clutch. Both flywheels are engaged with one another by an energizing member in the low speed range of said engine. Both are disengaged from one another by means of excitation control of the electromagnetic clutch in the high speed range of the engine. A generator driven by the engine rotating shaft is connected in series with the electromagnetic clutch and a battery.

  11. Early hominin auditory capacities.

    PubMed

    Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G; Thackeray, J Francis; Arsuaga, Juan Luis

    2015-09-01

    Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats.

  12. Early hominin auditory capacities

    PubMed Central

    Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J.; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G.; Thackeray, J. Francis; Arsuaga, Juan Luis

    2015-01-01

    Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats. PMID:26601261

  13. Heat Capacity in Proteins

    NASA Astrophysics Data System (ADS)

    Prabhu, Ninad V.; Sharp, Kim A.

    2005-05-01

    Heat capacity (Cp) is one of several major thermodynamic quantities commonly measured in proteins. With more than half a dozen definitions, it is the hardest of these quantities to understand in physical terms, but the richest in insight. There are many ramifications of observed Cp changes: The sign distinguishes apolar from polar solvation. It imparts a temperature (T) dependence to entropy and enthalpy that may change their signs and which of them dominate. Protein unfolding usually has a positive ΔCp, producing a maximum in stability and sometimes cold denaturation. There are two heat capacity contributions, from hydration and protein-protein interactions; which dominates in folding and binding is an open question. Theoretical work to date has dealt mostly with the hydration term and can account, at least semiquantitatively, for the major Cp-related features: the positive and negative Cp of hydration for apolar and polar groups, respectively; the convergence of apolar group hydration entropy at T ≈ 112°C; the decrease in apolar hydration Cp with increasing T; and the T-maximum in protein stability and cold denaturation.

  14. Psychiatric Issues in Palliative Care: Assessing Mental Capacity

    PubMed Central

    Udo, Itoro; Mohammed, Zeid; Gash, Amanda

    2013-01-01

    Issues surrounding capacity to consent to or refuse treatment are increasingly receiving clinical and legal attention. Through the use of 3 case vignettes that involve different aspects of mental health care in palliative care settings, mental capacity issues are discussed. The vignettes tackle capacity in a patient with newly developed mental illness consequent to physical illness, capacity in a patient with mental illness but without delirium and capacity in a patient with known impairment of the mind. These discussions give credence to best practice position where physicians act in the best interests of their patients at all times. It is important to emphasize that capacity decisions have to be made on a case by case basis, within the remit of legal protection. This is a fundamental requirement of the Mental Capacity Act 2005, England & Wales (MCA). The later is used as the legal basis for these discussions. The psychiatric liaison service is a useful resource to provide consultation, advice and or joint assessment to clinicians encountering complex dilemmas involving decision-making capacity. PMID:25278761

  15. Decisional Capacity in Amyotrophic Lateral Sclerosis.

    PubMed

    Khin Khin, Eindra; Minor, Darlinda; Holloway, Amanda; Pelleg, Ayla

    2015-06-01

    The cognitive and behavioral changes that can be observed in the neurodegenerative terminal disease amyotrophic lateral sclerosis (ALS), once characterized as purely a motor neuron disease, have become increasingly recognized over the past century. Detecting cognitive deficits earlier and identifying continued changes at regular intervals can lead to improved care, proactive treatments, and earlier discussions about end-of-life wishes. Although medical decisional capacity is required for every treatment decision made, its importance becomes paramount when making decisions on complex medical treatments that will invariably and significantly affect quality of life or life itself. In this review, we conducted a critical analysis of the evidence-based literature on the cognitive and behavioral impairments in ALS that can compromise medical decisional capacity. We review specific ALS-related clinical scenarios in which decisional capacity is of utmost importance and discuss a practical framework for cognitive and behavioral assessment that can be routinely and efficiently used, while being mindful of the confounding factors associated with ALS. Finally, we review models for preserving patient choices that can be used in patients with ALS to help safeguard autonomy and retain dignity toward the end of life.

  16. Mainstreaming the Hearing Impaired Student.

    ERIC Educational Resources Information Center

    Szelazkiewicz, Sara

    This review of the literature on mainstreaming students with hearing impairments begins by defining "hearing impairment,""deafness," and "hard of hearing". The paper briefly considers causes of hearing impairments and types of hearing impairments. Suggestions for preparing a class for a student with hearing loss includes having a visible class…

  17. Trainable Mentally Impaired/Severely Multiply Impaired/Autistic Impaired/Severely Mentally Impaired. Product Evaluation Report 1989-1990.

    ERIC Educational Resources Information Center

    Claus, Richard N.; And Others

    The evaluation report describes special education services provided to trainable mentally impaired (TMI), autistic impaired (AI), severely multiply impaired (SXI), and severely mentally impaired (SMI) students at and through the Melvin G. Millet Learning Center (Bridgeport, Michigan). The eight program components are described individually and…

  18. Language Impairment in the Attention-Deficit/Hyperactivity Disorder Context

    ERIC Educational Resources Information Center

    Redmond, Sean M.

    2016-01-01

    Purpose: Attention-deficit/hyperactivity disorder (ADHD) is a ubiquitous designation that affects the identification, assessment, treatment, and study of pediatric language impairments (LIs). Method: Current literature is reviewed in 4 areas: (a) the capacity of psycholinguistic, neuropsychological, and socioemotional behavioral indices to…

  19. Language Impairment in the Attention-Deficit/Hyperactivity Disorder Context

    ERIC Educational Resources Information Center

    Redmond, Sean M.

    2016-01-01

    Purpose: Attention-deficit/hyperactivity disorder (ADHD) is a ubiquitous designation that affects the identification, assessment, treatment, and study of pediatric language impairments (LIs). Method: Current literature is reviewed in 4 areas: (a) the capacity of psycholinguistic, neuropsychological, and socioemotional behavioral indices to…

  20. Sustained Attention in Children with Specific Language Impairment (SLI)

    ERIC Educational Resources Information Center

    Finneran, Denise A.; Francis, Alexander L.; Leonard, Laurence B.

    2009-01-01

    Purpose: Information-processing limitations have been associated with language problems in children with specific language impairment (SLI). These processing limitations may be associated with limitations in attentional capacity, even in the absence of clinically significant attention deficits. In this study, the authors examined the performance…

  1. Advanced work capacity testing.

    PubMed

    Bretz, Károly J; Dános, László; Smudla, Szilvia; Pálosi, Adrienn

    2015-01-01

    The aim of this study is to describe an accurate work capacity testing which can be used in the industry, as well as in rehabilitation process. The first part of this paper is dealing with the NIOSH lifting equation, which is a tool used by occupational health and safety professionals. The second part of this paper summarizes the features and applications of the "ErgoScope" work simulator. Static and dynamic strength of upper and lower limbs, as well as whole body efforts can be measured. The equipment makes it possible to evaluate pushing, pulling, lifting and carrying activities comprising reaching, bending and stooping movements. In the third part of this paper we demonstrate handgrip force data recorded using the "ErgoScope" work simulator comparing with handgrip force data published in the literature. "ErgoScope" work simulator is capable to measure handgrip and pinch forces, suitable to evaluate fine motor skills, hand and finger dexterity, as well as reaction times.

  2. Social communication impairments: pragmatics.

    PubMed

    Russell, Robert L

    2007-06-01

    Social communication or pragmatic impairments are characterized and illustrated as involving inappropriate or ineffective use of language and gesture in social contexts. Three clinical vignettes illustrate different pragmatic impairments and the wealth of diagnostic information that can be garnered from observation of a child's social communication behavior. Definitions of, and developmental milestones in, domains of pragmatic competence are provided. Several screening instruments are suggested for use in assessing pragmatic competence within the time-frame of a pediatric examination. Frequent comorbid psychiatric conditions are described and a sample of current neurobiologic research is briefly summarized.

  3. Cognitive Impairment among the Aging Population in a Community in Southwest Nigeria

    ERIC Educational Resources Information Center

    Adebiyi, Akindele O.; Ogunniyi, Adesola; Adediran, Babatunde A.; Olakehinde, Olaide O.; Siwoku, Akeem A.

    2016-01-01

    Background: Vascular risk models can be quite informative in assisting the clinician to make a prediction of an individual's risk of cognitive impairment. Thus, a simple marker is a priority for low-capacity settings. This study examines the association of selected simple to deploy vascular markers with cognitive impairment in an elderly…

  4. Oral Morphosyntactic Competence as a Predictor of Reading Comprehension in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Buil-Legaz, Lucía; Aguilar-Mediavilla, Eva; Rodríguez-Ferreiro, Javier

    2016-01-01

    Background: Children with a diagnosis of specific language impairment (SLI) present impaired oral comprehension. According to the simple view of reading, general amodal linguistic capacity accounts for both oral and reading comprehension. Considering this, we should expect SLI children to display a reading comprehension deficit. However, previous…

  5. Oral Morphosyntactic Competence as a Predictor of Reading Comprehension in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Buil-Legaz, Lucía; Aguilar-Mediavilla, Eva; Rodríguez-Ferreiro, Javier

    2016-01-01

    Background: Children with a diagnosis of specific language impairment (SLI) present impaired oral comprehension. According to the simple view of reading, general amodal linguistic capacity accounts for both oral and reading comprehension. Considering this, we should expect SLI children to display a reading comprehension deficit. However, previous…

  6. Cognitive Impairment among the Aging Population in a Community in Southwest Nigeria

    ERIC Educational Resources Information Center

    Adebiyi, Akindele O.; Ogunniyi, Adesola; Adediran, Babatunde A.; Olakehinde, Olaide O.; Siwoku, Akeem A.

    2016-01-01

    Background: Vascular risk models can be quite informative in assisting the clinician to make a prediction of an individual's risk of cognitive impairment. Thus, a simple marker is a priority for low-capacity settings. This study examines the association of selected simple to deploy vascular markers with cognitive impairment in an elderly…

  7. North American fertilizer capacity data

    SciTech Connect

    Not Available

    1991-01-01

    This listing of producers and their fertilizer production capacities was compiled in January 1991 with the cooperation of the US and Canadian fertilizer industry. Capacity is only an indicator of supply. Nameplate capacity differs from planned production levels or actual production because plants often operate above or below design capacity. Unless reported otherwise, plant capacities are based on 340 days per year of operation. No adjustment is made for partial year operation. Numerical data for the production of ammonia, ammonium nitrate, nitrogen solutions, urea, phosphate rock, phosphoric acid and ammonium phosphates is included.

  8. Ethical Considerations in Electronic Monitoring of the Cognitively Impaired.

    PubMed

    Yang, Y Tony; Kels, Charles G

    2017-01-01

    Cognitive impairment afflicts an estimated 16 million people in the United States. Wandering is a concerning behavior associated with cognitive impairment, as it may threaten patient safety. The risks posed by wandering place severe burdens on both professional and informal caregivers, as well as law enforcement institutions throughout the United States. As such, location trackers that could reduce this burden have become increasingly prevalent. As with many assistive technologies, the substantial promise of location trackers is counterbalanced by potential pitfalls with respect to loss of privacy and autonomy. This article reviews the ethical issues raised by electronic monitoring of cognitively impaired persons, with the goal of transcending a narrow focus on decisional capacity in favor of a patient-centered framework that is applicable and adjustable at different stages of cognitive decline. Balancing the ethical principles of beneficence and respect in treating cognitively impaired persons goes beyond the necessary step of evaluating decision-making capacity to include partnering with families, caretakers, and cognitively impaired individuals who wander in a collaborative coalition of care. An approach emphasizing the individual needs of patients and caretakers is best suited to finding solutions that implement tracking technologies in ways that both protect and empower the cognitively impaired.

  9. The influence of lung function on exercise capacity in patients with type 2 diabetes.

    PubMed

    Kitahara, Yoshihiro; Hattori, Noboru; Yokoyama, Akihito; Yamane, Kiminori; Sekikawa, Kiyokazu; Inamizu, Tsutomu; Kohno, Nobuoki

    2010-03-01

    Patients with type 2 diabetes have impaired exercise capacity. While numerous factors are known to contribute to impaired exercise capacity, the role of lung function remains unclear. We conducted the present study to investigate the influence of lung function on exercise capacity in patients with type 2 diabetes. Cardiopulmonary exercise testing was carried out in 31 male patients with type 2 diabetes without diabetic complications or cardiopulmonary diseases. Patients with abnormal spirometry results such as a percentage of predicted forced vital capacity (%FVC) < 80% and/or a ratio of forced expiratory volume in one second (FEV1) to FVC (FEV1/FVC) < 70% were excluded from the study. We used the percentage of predicted maximal oxygen uptake (%VO2max) as an index of exercise capacity. The correlations between %VO2max and lung function and other factors known to be associated with impaired exercise capacity were then assessed. Univariate analysis revealed %VO2max correlated significantly with percentage of predicted FEV1 (%FEV1), duration of type 2 diabetes, regular exercise habits, and systolic and diastolic blood pressures. In a multivariate analysis, %FEV1 and regular exercise habits were found to be independent determinants of %VO2max. A mild reduction in %FEV1, which may be a complication of diabetes, is associated with impaired exercise capacity in patients with type 2 diabetes. When evaluating spirometric values in patients with type 2 diabetes, a reduction in %FEV1 should be noted even when both %FVC and FEV1/FVC are within normal limits.

  10. Continuity of Quantum Channel Capacities

    NASA Astrophysics Data System (ADS)

    Leung, Debbie; Smith, Graeme

    2009-11-01

    We prove that a broad array of capacities of a quantum channel are continuous. That is, two channels that are close with respect to the diamond norm have correspondingly similar communication capabilities. We first show that the classical capacity, quantum capacity, and private classical capacity are continuous, with the variation on arguments {\\varepsilon} apart bounded by a simple function of {\\varepsilon} and the channel’s output dimension. Our main tool is an upper bound of the variation of output entropies of many copies of two nearby channels given the same initial state; the bound is linear in the number of copies. Our second proof is concerned with the quantum capacities in the presence of free backward or two-way public classical communication. These capacities are proved continuous on the interior of the set of non-zero capacity channels by considering mutual simulation between similar channels.

  11. Anarthria impairs subvocal counting.

    PubMed

    Cubelli, R; Nichelli, P; Pentore, R

    1993-12-01

    We studied subvocal counting in two pure anarthric patients. Analysis showed that they performed definitively worse than normal subjects free to articulate subvocally and their scores were in the lower bounds of the performances of subjects suppressing articulation. These results suggest that subvocal counting is impaired after anarthria.

  12. Aids for visual impairment.

    PubMed Central

    Dudley, N J

    1990-01-01

    This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue. Images FIG 1 FIG 3 FIG 4 FIG 5 FIG 6 FIG 7 FIG 8 FIG 9 FIG 10 PMID:2252929

  13. Emotionally Impaired Elementary Curriculum.

    ERIC Educational Resources Information Center

    Taulbee, Dianne R.; And Others

    A curriculum is presented for teaching emotionally impaired elementary students. The curriculum document describes program management techniques, strategies for developing and maintaining teacher-student relationships, and therapy/change systems. It outlines referral and eligibility procedures and exit criteria. It contains job descriptions for…

  14. Emotionally Impaired Elementary Curriculum.

    ERIC Educational Resources Information Center

    Taulbee, Dianne R.; And Others

    The Jackson County (Michigan) Intermediate School District curriculum for teaching emotionally impaired elementary students is presented. The curriculum document describes program management techniques, strategies for developing and maintaining teacher-student relationships, and therapy/change systems. It outlines referral and eligibility…

  15. Vestibular Impairment in Dementia

    PubMed Central

    Harun, Aisha; Oh, Esther S.; Bigelow, Robin T.; Studenski, Stephanie; Agrawal, Yuri

    2017-01-01

    Objective Recent studies suggest an association between vestibular and cognitive function. The goal of the study was to investigate whether vestibular function was impaired in individuals with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) compared to cognitively normal individuals. Study Design Cross-sectional study. Setting Outpatient memory clinic and longitudinal observational study unit. Patients Older individuals ≥ 55 years with MCI or AD. Age, gender and education-matched normal controls were drawn from the Baltimore Longitudinal Study of Aging (BLSA). Intervention Saccular and utricular function was assessed with cervical and ocular vestibular-evoked myogenic potentials (c- and oVEMPs) respectively, and horizontal semicircular canal function was assessed with video head impulse testing. Main Outcome Measures Presence or absence of VEMP responses, VEMP amplitude and vestibular ocular reflex (VOR) gain were measured. Results Forty-seven individuals with cognitive impairment (MCI N=15 and AD N=32) underwent testing and were matched with 94 controls. In adjusted analyses, bilaterally absent cVEMPs were associated with an over three-fold odds of AD (OR 3.42, 95% CI 1.33–8.91, p=0.011). One microvolt increases in both cVEMP and oVEMP amplitudes were associated with decreased odds of AD (OR 0.28, 95% CI 0.09–0.93, p=0.038 and OR 0.92, 95% CI 0.85–0.99, p=0.036, respectively). There was no significant difference in VOR gain between the groups. Conclusions These findings confirm and extend emerging evidence of an association between vestibular dysfunction and cognitive impairment. Further investigation is needed to determine the causal direction for the link between peripheral vestibular loss and cognitive impairment. PMID:27466890

  16. Vestibular Impairment in Dementia.

    PubMed

    Harun, Aisha; Oh, Esther S; Bigelow, Robin T; Studenski, Stephanie; Agrawal, Yuri

    2016-09-01

    Recent studies suggest an association between vestibular and cognitive function. The goal of the study was to investigate whether vestibular function was impaired in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with cognitively normal individuals. Cross-sectional study. Outpatient memory clinic and longitudinal observational study unit. Older individuals ≥55 years with MCI or AD. Age, sex, and education-matched normal controls were drawn from the Baltimore Longitudinal Study of Aging (BLSA). Saccular and utricular function was assessed with cervical and ocular vestibular-evoked myogenic potentials (c- and oVEMPs) respectively, and horizontal semicircular canal function was assessed with video head impulse testing. Presence or absence of VEMP responses, VEMP amplitude, and vestibular ocular reflex (VOR) gain were measured. Forty-seven individuals with cognitive impairment (MCI N = 15 and AD N = 32) underwent testing and were matched with 94 controls. In adjusted analyses, bilaterally absent cVEMPs were associated with an over three-fold odds of AD (OR 3.42, 95% CI 1.33-8.91, p = 0.011). One microvolt increases in both cVEMP and oVEMP amplitudes were associated with decreased odds of AD (OR 0.28, 95% CI 0.09-0.93, p = 0.038 and OR 0.92, 95% CI 0.85-0.99, p = 0.036, respectively). There was no significant difference in VOR gain between the groups. These findings confirm and extend emerging evidence of an association between vestibular dysfunction and cognitive impairment. Further investigation is needed to determine the causal direction for the link between peripheral vestibular loss and cognitive impairment.

  17. [Exercise capacity after heart valve replacement].

    PubMed

    Horstkotte, D; Niehues, R; Schulte, H D; Strauer, B E

    1994-01-01

    Exercise capacity following heart-valve replacement is dependent on how close to normal the artificial device can restore valve function, to what degree a preoperative impaired myocardial function and/or an increased pulmonary vascular resistance is normalized. The postoperative functional result can be determined by the subjective improvement of the patient, his functional capacity, exercise capacity, the central hemodynamics at rest and during exercise, and the systolic and diastolic function of the left and right ventricular myocardium. The subjective improvement of individual symptoms is obviously dependent on the degree of postoperative normalization of hemodynamics, especially of pressures in the pulmonary circulation. Subjective improvement can be objectified by comparing the functional capacities before and after surgery. Post-operative normalization of central hemodynamics and myocardial function does not happen immediately but within 3 to more than 12 months. A 12-month period can generally be expected in patients with mitral stenosis and increased pulmonary vascular resistance (> 400 dyn.sec.cm-5) prior to surgery. In patients with mitral and aortic regurgitation as well as with aortic stenosis and preoperative decrease of their left ventricular ejection fraction during exercise, continuous improvement of left ventricular pump function also may need up to 12 months. Physiological hemodynamic conditions generally are not restored by valve replacement. All prostheses are stenotic to forward blood flow because of the obstruction created by the narrowing of the valve area by sewing cuff and valve poppet. This may result in a hemodynamically important stenosis, especially after atrio-ventricular valve implantation, and may limit subjective and functional improvement. Exercise capacity after aortic valve replacement depends mainly on whether or not myocardial damage persists postoperatively. A workload of 1.5 w/kg body weight (BW) has been performed by 100% of

  18. VAP-CAP: A Procedure to Assess the Visual Functioning of Young Visually Impaired Children.

    ERIC Educational Resources Information Center

    Blanksby, D. C.; Langford, P. E.

    1993-01-01

    This article describes a visual assessment procedure (VAP) which evaluates capacity, attention, and processing (CAP) of infants and preschool children with visual impairments. The two-level battery considers, first, visual capacity and basic visual attention and, second, visual perceptual and cognitive abilities. A theoretical analysis of the…

  19. VAP-CAP: A Procedure to Assess the Visual Functioning of Young Visually Impaired Children.

    ERIC Educational Resources Information Center

    Blanksby, D. C.; Langford, P. E.

    1993-01-01

    This article describes a visual assessment procedure (VAP) which evaluates capacity, attention, and processing (CAP) of infants and preschool children with visual impairments. The two-level battery considers, first, visual capacity and basic visual attention and, second, visual perceptual and cognitive abilities. A theoretical analysis of the…

  20. Grammatical Impairments in PPA

    PubMed Central

    Thompson, Cynthia K.; Mack, Jennifer E.

    2015-01-01

    Background Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. Aims We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. Main Contribution PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Conclusions Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real

  1. Bioethics for clinicians: 3. Capacity.

    PubMed Central

    Etchells, E; Sharpe, G; Elliott, C; Singer, P A

    1996-01-01

    In the context of patient consent, "capacity" refers to the patient's ability to understand information relevant to a treatment decision and to appreciate the reasonably foreseeable consequences of a decision or lack of decision. A person may be "capable" with respect to one decision but not with respect to another. Clinicians can usually identify patients who are clearly capable or incapable, but in some cases a clinical capacity assessment is required. Such assessment may consist of cognitive status testing, general impressions of capacity or specific capacity assessment. Specific capacity assessment, in which the clinician evaluates the patient's ability to understand pertinent information and appreciate its implications, is probably the optimal method. When conducting a specific capacity assessment, the clinician must ensure that the disclosure of information is effective and must evaluate the patient's reason for his or her decision. If the assessment suggests that the patient is incapable, further assessment is generally recommended. PMID:8823211

  2. Chemistry for the Visually Impaired.

    ERIC Educational Resources Information Center

    Ratliff, Judy L.

    1997-01-01

    Discusses modifications to general education or introductory chemistry courses that allow visually impaired students to participate productively. Describes a strategy for teaching about elements and density, and the construction of a conductivity tester for visually impaired students. (JRH)

  3. Impaired Consciousness in Epilepsy

    PubMed Central

    Blumenfeld, Hal

    2013-01-01

    Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost making it impossible for the individual to experience or respond. This has huge consequences for safety, productivity, emotional health and quality of life. To prevent impaired consciousness in epilepsy it is necessary to understand the mechanisms leading to brain dysfunction during seizures. Normally the “consciousness system”—a specialized set of cortical-subcortical structures—maintains alertness, attention and awareness. Recent advances in neuroimaging, electrophysiology and prospective behavioral testing have shed new light on how epileptic seizures disrupt the consciousness system. Diverse seizure types including absence, generalized tonic-clonic and complex partial seizures converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding these mechanisms may lead to improved treatment strategies to prevent impaired consciousness and improve quality of life in people with epilepsy. PMID:22898735

  4. Treatment consent capacity in patients with traumatic brain injury across a range of injury severity

    PubMed Central

    Triebel, K.L.; Martin, R.C.; Novack, T.A.; Dreer, L.; Turner, C.; Pritchard, P.R.; Raman, R.

    2012-01-01

    Objective: To investigate medical decision-making capacity (MDC) in patients with acute traumatic brain injury (TBI) across a range of injury severity. Methods: We evaluated MDC cross-sectionally 1 month after injury in 40 healthy controls and 86 patients with TBI stratified by injury severity (28 mild [mTBI], 15 complicated mild [cmTBI], 43 moderate/severe [msevTBI]). We compared group performance on the Capacity to Consent to Treatment Instrument and its 5 consent standards (expressing choice, reasonable choice, appreciation, reasoning, understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, severe impairment) on the consent standards were also assigned to each participant with TBI using cut scores referenced to control performance. Results: One month after injury, the mTBI group performed equivalently to controls on all consent standards. In contrast, the cmTBI group was impaired relative to controls on the understanding standard. No differences emerged between the mTBI and cmTBI groups. The msevTBI group was impaired on almost all standards relative to both control and mTBI groups, and on the understanding standard relative to the cmTBI group. Capacity compromise (mild/moderate or severe impairment ratings) on the 3 clinically complex standards (understanding, reasoning, appreciation) occurred in 10%–30% of patients with mTBI, 50% of patients with cmTBI, and 50%–80% of patients with msevTBI. Conclusions: One month following injury, MDC is largely intact in patients with mTBI, but is impaired in patients with cmTBI and msevTBI. Impaired MDC is prevalent in acute TBI and is strongly related to injury severity. PMID:22496195

  5. Adaptive capacity and its assessment

    SciTech Connect

    Engle, Nathan L.

    2011-04-20

    This paper reviews the concept of adaptive capacity and various approaches to assessing it, particularly with respect to climate variability and change. I find that adaptive capacity is a relatively under-researched topic within the sustainability science and global change communities, particularly since it is uniquely positioned to improve linkages between vulnerability and resilience research. I identify opportunities for advancing the measurement and characterization of adaptive capacity by combining insights from both vulnerability and resilience frameworks, and I suggest several assessment approaches for possible future development that draw from both frameworks and focus on analyzing the governance, institutions, and management that have helped foster adaptive capacity in light of recent climatic events.

  6. Age-Related Sensory Impairments and Risk of Cognitive Impairment.

    PubMed

    Fischer, Mary E; Cruickshanks, Karen J; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara E K; Klein, Ronald; Tweed, Ted S

    2016-10-01

    To evaluate the associations between sensory impairments and 10-year risk of cognitive impairment. The Epidemiology of Hearing Loss Study (EHLS), a longitudinal, population-based study of aging in the Beaver Dam, Wisconsin community. Baseline examinations were conducted in 1993 and follow-up examinations have been conducted every 5 years. General community. EHLS members without cognitive impairment at EHLS-2 (1998-2000). There were 1,884 participants (mean age 66.7) with complete EHLS-2 sensory data and follow-up information. Cognitive impairment was defined as a Mini-Mental State Examination score of <24 or history of dementia or Alzheimer's disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5, 1, 2, 4 kHz) of >25 dB hearing level in either ear, visual impairment was a Pelli-Robson contrast sensitivity of <1.55 log units in the better eye, and olfactory impairment was a San Diego Odor Identification Test score of <6. Hearing, visual, and olfactory impairment were independently associated with cognitive impairment risk (hearing: hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.11-3.26; vision: HR = 2.05, 95% CI = 1.24-3.38; olfaction: HR = 3.92, 95% CI = 2.45-6.26)). Nevertheless, 85% of participants with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. The relationship between sensory impairment and cognitive impairment was not unique to one sensory system, suggesting that sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  7. The Capacity to Build Organizational Capacity in Schools

    ERIC Educational Resources Information Center

    King, M. Bruce; Bouchard, Kate

    2011-01-01

    Purpose: Reformers, policymakers, and researchers have given considerable attention to organizational capacity in schools, especially in those schools that perpetuate or exacerbate achievement gaps among diverse student groups and reproduce social inequalities. There is an emerging consensus about key dimensions of school capacity and how they can…

  8. The Capacity to Build Organizational Capacity in Schools

    ERIC Educational Resources Information Center

    King, M. Bruce; Bouchard, Kate

    2011-01-01

    Purpose: Reformers, policymakers, and researchers have given considerable attention to organizational capacity in schools, especially in those schools that perpetuate or exacerbate achievement gaps among diverse student groups and reproduce social inequalities. There is an emerging consensus about key dimensions of school capacity and how they can…

  9. Butalbital and driving impairment.

    PubMed

    Yeakel, Jillian K; Logan, Barry K

    2013-07-01

    Butalbital (Fiorinal(®)), used in the treatment of migraines and muscle pain, is the most commonly encountered barbiturate in impaired driving cases. It has central nervous system (CNS) depressant properties, including sedation, drowsiness, and feelings of intoxication, which can contribute to driving impairment. Twenty-six driving under the influence cases are reviewed including results from field sobriety tests and toxicology testing. Blood samples were screened using enzyme multiplied immunoassay technique immunoassay, and the presence of butalbital was confirmed and quantified using gas chromatography/mass spectrometry, gas chromatography with flame ionization detection, or gas chromatography nitrogen/phosphorus detection. Butalbital concentrations ranged from 1.0 to 30.2 mg/L, with a mean and median of 16.0 mg/L. General impairment indicators in these cases included horizontal and vertical nystagmus, lack of convergence, poor motor coordination, and balance and speech problems, which are common to CNS depressant intoxication, similar to that associated with alcohol. These findings indicate the importance of toxicological testing for butalbital in cases where CNS depressants are indicated. © 2013 American Academy of Forensic Sciences.

  10. Attentional control mediates the relationship between social anhedonia and social impairment

    PubMed Central

    Tully, Laura M.; Lincoln, Sarah Hope; Hooker, Christine I.

    2014-01-01

    Social anhedonia (SA), a trait-like disinterest in social contact and diminished capacity to experience pleasure from social interactions, is consistently associated with social impairments in both healthy and clinical populations. However, the mechanisms underlying the relationship between SA and social impairment are poorly understood. Attentional control, selecting and focusing on relevant information and inhibiting irrelevant, may be one such mechanism. We examined individual differences in SA, attentional control, and social impairment in 108 healthy adults. High SA related to low attentional control and high social impairment. Moreover, attentional control mediated the relationship between SA and social impairment, establishing attentional control as one mechanism underlying aberrations in the fundamental human need for social contact. Although both attentional deficits and social impairment have been separately noted in SA, the relationship between SA, attentional control and social impairment in this non-clinical sample reflects a novel contribution. PMID:25538647

  11. [Exercise capacity in patients with pulmonary sarcoidosis].

    PubMed

    Błaut-Jurkowska, Justyna; Knap, Klaudia; Kaźnica-Wiatr, Magdalena; Żygadło, Agnieszka; Tomkiewicz-Pająk, Lidia; Podolec, Piotr; Olszowska, Maria

    2017-08-21

    Exertional dyspnea is a common manifestation of sarcoidosis. Cardiopulmonary exercise testing (CPET) is a useful tool to evaluate exercise tolerance of sarcoid patients. The aim of the study was to evaluate of exercise capacity in patients with pulmonary sarcoidosis with regard to duration of the disease. Analysis of differences in physical tolerance between patients with cardiac sarcoidosis and without cardiac sarcoidosis. 39 patients diagnosed with pulmonary sarcoidosis were enrolled to our study. Cardiopulmonary exercise test was used to assess exercise capacity. According to time passed from diagnosis of sarcoidosis patients were grouped into 2 groups. Cardiac sarcoidosis was diagnosed in 9 subjects (23.07%). The control group consisted of 33 healthy volunteers. The results of the ergospirometry test in patients with lung sarcoidosis showed statistically significant differences in comparison to the control group. The age of patients with pulmonary sarcoidosis correlated negatively with maximal heart rate, oxygen consumption at peak exercise and at anaerobic threshold, breathing frequency at peak exercise, minute ventilation at peak exercise and metabolic equivalent. There was a negative, statistically significant correlation between the oxygen pulse at the peak of exercise and the treatment of steroids in the past. Exercise limitation in patients with pulmonary sarcoidosis is a consequence of both ventilatory and cardiocirculatory impairment. Patients with longer disease history of sarcoidosis achieved worse results at cardiopulmonary exercise test than patients with shorter disease history. Trend towards worse exercise tolerance in patients with cardiac sarcoidosis compared to patients without cardiac sarcoidosis was observed.

  12. Working memory contributions to reinforcement learning impairments in schizophrenia.

    PubMed

    Collins, Anne G E; Brown, Jaime K; Gold, James M; Waltz, James A; Frank, Michael J

    2014-10-08

    Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n = 49) and healthy controls (n = 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia.

  13. Neurological Impairment: Nomenclature and Consequences.

    ERIC Educational Resources Information Center

    Spears, Catherine E.; Weber, Robert E.

    Neurological impairment as discussed includes a range of disabilities referred to as neurological impairment: minimal brain dysfunction/damage, developmental disability, perceptual handicap, learning disability, hyperkinetic behavioral syndrome, and others. Defined are causes of neurological impairment and methods of diagnosis. Symptoms…

  14. Assessment of Hearing Impaired Youth.

    ERIC Educational Resources Information Center

    Hicks, Doin E., Ed.; And Others

    1980-01-01

    The issue of Directions contains 11 articles on assessment of hearing impaired individuals. Entries have the following titles and authors: "Classroom Assessment Techniques for Hearing Impaired Students--A Literature Review" (B. McKee, M. Hausknecht); "Informal Assessment of Hearing Impaired Students In the Classroom" (B. Culhane, R. Hein);…

  15. Assessment of Hearing Impaired Youth.

    ERIC Educational Resources Information Center

    Hicks, Doin E., Ed.; And Others

    1980-01-01

    The issue of Directions contains 11 articles on assessment of hearing impaired individuals. Entries have the following titles and authors: "Classroom Assessment Techniques for Hearing Impaired Students--A Literature Review" (B. McKee, M. Hausknecht); "Informal Assessment of Hearing Impaired Students In the Classroom" (B. Culhane, R. Hein);…

  16. Plasma antioxidant capacity is reduced in Asperger syndrome.

    PubMed

    Parellada, Mara; Moreno, Carmen; Mac-Dowell, Karina; Leza, Juan Carlos; Giraldez, Marisa; Bailón, Concepción; Castro, Carmen; Miranda-Azpiazu, Patricia; Fraguas, David; Arango, Celso

    2012-03-01

    Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Accurate perception of negative emotions predicts functional capacity in schizophrenia.

    PubMed

    Abram, Samantha V; Karpouzian, Tatiana M; Reilly, James L; Derntl, Birgit; Habel, Ute; Smith, Matthew J

    2014-04-30

    Several studies suggest facial affect perception (FAP) deficits in schizophrenia are linked to poorer social functioning. However, whether reduced functioning is associated with inaccurate perception of specific emotional valence or a global FAP impairment remains unclear. The present study examined whether impairment in the perception of specific emotional valences (positive, negative) and neutrality were uniquely associated with social functioning, using a multimodal social functioning battery. A sample of 59 individuals with schizophrenia and 41 controls completed a computerized FAP task, and measures of functional capacity, social competence, and social attainment. Participants also underwent neuropsychological testing and symptom assessment. Regression analyses revealed that only accurately perceiving negative emotions explained significant variance (7.9%) in functional capacity after accounting for neurocognitive function and symptoms. Partial correlations indicated that accurately perceiving anger, in particular, was positively correlated with functional capacity. FAP for positive, negative, or neutral emotions were not related to social competence or social attainment. Our findings were consistent with prior literature suggesting negative emotions are related to functional capacity in schizophrenia. Furthermore, the observed relationship between perceiving anger and performance of everyday living skills is novel and warrants further exploration.

  18. Beyond Capacity Limitations: Determinants of Word Recall Performance on Verbal Working Memory Span Tasks in Children with SLI

    ERIC Educational Resources Information Center

    Mainela-Arnold, Elina; Evans, Julia L.

    2005-01-01

    Reduced verbal working memory capacity has been proposed as a possible account of language impairments in specific language impairment (SLI). Studies have shown, however, that differences in strength of linguistic representations in the form of word frequency affect list recall and performance on verbal working memory tasks. This suggests that…

  19. Concrete Operations and Attentional Capacity.

    ERIC Educational Resources Information Center

    Chapman, Michael; Lindenberger, Ulman

    1989-01-01

    To test predictions regarding the attentional capacity requirements of Piaget's stage of concrete operations, a battery of concrete operational tasks and two measures of attentional capacity were administered to 120 first-, second-, and third-graders. Findings concern class inclusion, transitivity of length and weight, and multiplication of…

  20. Concrete Operations and Attentional Capacity.

    ERIC Educational Resources Information Center

    Chapman, Michael; Lindenberger, Ulman

    1989-01-01

    To test predictions regarding the attentional capacity requirements of Piaget's stage of concrete operations, a battery of concrete operational tasks and two measures of attentional capacity were administered to 120 first-, second-, and third-graders. Findings concern class inclusion, transitivity of length and weight, and multiplication of…

  1. Contemporaneous assessment of testamentary capacity.

    PubMed

    Shulman, Kenneth I; Peisah, Carmelle; Jacoby, Robin; Heinik, Jeremia; Finkel, Sanford

    2009-06-01

    Challenges to wills on the basis of lack of testamentary capacity and/or undue influence are likely to increase over the next generation. Since contemporaneous assessment of testamentary capacity can be a powerful influence on the outcome of such challenges, there will be an associated increase in requests for expert assessment of testamentary capacity. There is a need to provide such potential experts with the knowledge and guidelines necessary to conduct assessments that will be helpful to the judicial system. A subcommittee of the International Psychogeriatric Association (IPA) task force on "Testamentary Capacity and Undue Influence" was formed to establish guidelines for contemporaneous assessment of testamentary capacity. The task-specific criteria for testamentary capacity as outlined by Lord Chief Justice Cockburn in the well-known Banks v. Goodfellow case are described. Additional issues are identified for probing and documentation. This is designed to determine whether the testator can formulate a coherent, rational testamentary plan that connects his/her beliefs, values and relationships with the proposed disposition of assets. Rules of engagement by the expert assessor are defined as well as an approach to the clinical examination for testamentary capacity resulting in a clear and relevant report. Guidelines for experts who are asked to provide a contemporaneous opinion on testamentary capacity should help to inform disputes resulting from challenges to wills. A consistent clinical approach will help the courts to make their determinations.

  2. Heat capacity, configurational heat capacity and fragility of hydrous magmas

    NASA Astrophysics Data System (ADS)

    Di Genova, D.; Romano, C.; Giordano, D.; Alletti, M.

    2014-10-01

    The glassy and liquid heat capacities of four series of dry and hydrous natural glasses and magma as a function of temperature and water content (up to 19.9 mol%) were investigated using differential scanning calorimetry (DSC). The analyzed compositions are basalt, latite, trachyte and pantellerite. The results of this study indicate that the measured heat capacity of glasses (Cpg) is a linear function of composition and is well reproduced by the empirical model of Richet (1987). For the investigated glasses, the partial molar heat capacity of water can be considered as independent of composition, in agreement with Bouhifd et al. (2006). For hydrous liquids, the heat capacity (Cpliq) decreases nonlinearly with increasing water content. Previously published models, combined with the partial molar heat capacity of water from the literature, are not able to reproduce our experimental data in a satisfactory way. We estimated the partial molar heat capacity of water (CpH2O) in hydrous magma over a broad compositional range. The proposed value is 41 ± 3 J mol-1 K-1. Water strongly affects the configurational heat capacity at the glass transition temperature [Cpconf (Tg)]. An increases of Cpconf (Tg) with water content was measured for the polymerized liquids (trachyte and pantellerite), while the opposite behavior was observed for the most depolymerized liquids (basalt and latite). Structural and rheological implications of this behavior are discussed in light of the presented results.

  3. North American fertilizer capacity data

    SciTech Connect

    Not Available

    1993-02-01

    This listing of fertilizer producers and their production capacities was compiled in February 1993 with the cooperation of the US and Canadian fertilizer industry. TVA does not guarantee the completeness or accuracy of the information. Capacity is only an indicator of supply. Nameplate capacity differs from planned production levels or actual production because plants often operate above or below design capacity. Unless reported otherwise, plant capacities are based on 340 days per year of operation. No adjustment is made for partial year operation. Information is given on the following types of fertilizers: ammonia, ammonium nitrate, nitrogen solutions, urea, ammonium sulfate, phosphate rock, wet-process phosphoric acid, ammonium phosphates, concentrated superphosphates, potash, nitric acid, superphosphoric acid, upgraded phosphoric acids, normal superphosphate, elemental phosphorus, potassium sulfate, and sulfate of potash/magnesia.

  4. Mild Cognitive Impairment.

    PubMed

    Sanford, Angela M

    2017-08-01

    Mild cognitive impairment (MCI) occurs along a continuum from normal cognition to dementia. A roadblock to earlier diagnosis and potential treatment is the lack of consistency with screening for MCI. Universal screening would be ideal, but is limited. Once a diagnosis of MCI is made, it is important for the clinician to evaluate for reversible causes. At present time, there are no pharmacologic treatments proven to slow or cure progression of MCI to dementia; nonetheless, there is evidence that lifestyle modifications including diet, exercise, and cognitive stimulation may be effective. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Cognitive impairment and pragmatics.

    PubMed

    Gutiérrez-Rexach, Javier; Schatz, Sara

    2016-01-01

    One of the most important ingredients of felicitous conversation exchanges is the adequate expression of illocutionary force and the achievement of perlocutionary effects, which can be considered essential to the functioning of pragmatic competence. The breakdown of illocutionary and perlocutionary functions is one of the most prominent external features of cognitive impairment in Alzheimer's Disease, with devastating psychological and social consequences for patients, their family and caregivers. The study of pragmatic functions is essential for a proper understanding of the linguistic and communicative aspects of Alzheimer's disease.

  6. A collaborative approach to supporting communication in the assessment of decision-making capacity.

    PubMed

    Zuscak, Simon John; Peisah, Carmelle; Ferguson, Alison

    2016-01-01

    This paper explores the clinical implications of acquired communication disorders in decisional capacity. Discipline-specific contributions are discussed in a multidisciplinary context, with a specific focus on the role of speech and language pathologists (SLPs). Key rehabilitation issues in determining decisional capacity are identified. The impact of communication impairment on capacity is discussed in light of the research literature relating to supportive communication and collaborative practice that respects human rights. Guidelines are presented for professionals involved in the assessment of the decisional capacity of individuals with communication disorders of neurological origin. They guide an assessor through: assessing cognition, language and speech; determining preferred communication domains; and practical strategies and considerations for maximising communication. There is a dearth of guidelines available that deal with augmenting and supporting communication of individuals with acquired communication disorders of neurological origin when it comes to assessing legal decision-making capacity. Capacity assessment is a multidisciplinary realm, and the involvement of SLPs is key to maximising the decision-making capacity of these individuals. All clinicians have an obligation to maximise client autonomy and participation in decision-making. Assessments of capacity should involve a general cognitive ability assessment, followed by a decision-specific assessment tool or question set for the decision facing the patient. The involvement of speech and language pathologists (SLPs) is key to assess and facilitate capacity determinations in instances of cognitive-communication disorder. Impairments in different aspects of auditory comprehension require different accommodations.

  7. Search for Capacity-Limited and Super-Capacity Search.

    PubMed

    Han, Suk Won

    2017-05-01

    The present study investigated capacity limitations of visual search. In a series of experiments, participants searched for a singleton target among homogenous distractors, a conjunction target defined by combination of two features, or a feature target among heterogeneous distractors. Using the simultaneous-sequential paradigm, I found that singleton search proceeded in a capacity-unlimited manner. By contrast, the performance of the conjunction search was found to depend on a capacity-limited process. For feature searches, the performance of searching for a specific color was not affected by how the stimuli were presented, while the orientation search performance was enhanced as the number of distractors simultaneously presented with the target increased. These results imply that distinct colors are individually coded, whereas multiple orientations are encoded as an ensemble in a structured way. Taken together, the present study clarifies which type of search process are capacity-limited and reveals how this limit can be overcome.

  8. Interference and memory capacity limitations.

    PubMed

    Endress, Ansgar D; Szabó, Szilárd

    2017-10-01

    Working memory (WM) is thought to have a fixed and limited capacity. However, the origins of these capacity limitations are debated, and generally attributed to active, attentional processes. Here, we show that the existence of interference among items in memory mathematically guarantees fixed and limited capacity limits under very general conditions, irrespective of any processing assumptions. Assuming that interference (a) increases with the number of interfering items and (b) brings memory performance to chance levels for large numbers of interfering items, capacity limits are a simple function of the relative influence of memorization and interference. In contrast, we show that time-based memory limitations do not lead to fixed memory capacity limitations that are independent of the timing properties of an experiment. We show that interference can mimic both slot-like and continuous resource-like memory limitations, suggesting that these types of memory performance might not be as different as commonly believed. We speculate that slot-like WM limitations might arise from crowding-like phenomena in memory when participants have to retrieve items. Further, based on earlier research on parallel attention and enumeration, we suggest that crowding-like phenomena might be a common reason for the 3 major cognitive capacity limitations. As suggested by Miller (1956) and Cowan (2001), these capacity limitations might arise because of a common reason, even though they likely rely on distinct processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. Large capacity temporary visual memory

    PubMed Central

    Endress, Ansgar D.; Potter, Mary C.

    2014-01-01

    Visual working memory (WM) capacity is thought to be limited to three or four items. However, many cognitive activities seem to require larger temporary memory stores. Here, we provide evidence for a temporary memory store with much larger capacity than past WM capacity estimates. Further, based on previous WM research, we show that a single factor — proactive interference — is sufficient to bring capacity estimates down to the range of previous WM capacity estimates. Participants saw a rapid serial visual presentation (RSVP) of 5 to 21 pictures of familiar objects or words presented at rates of 4/s or 8/s, respectively, and thus too fast for strategies such as rehearsal. Recognition memory was tested with a single probe item. When new items were used on all trials, no fixed memory capacities were observed, with estimates of up to 9.1 retained pictures for 21-item lists, and up to 30.0 retained pictures for 100-item lists, and no clear upper bound to how many items could be retained. Further, memory items were not stored in a temporally stable form of memory, but decayed almost completely after a few minutes. In contrast, when, as in most WM experiments, a small set of items was reused across all trials, thus creating proactive interference among items, capacity remained in the range reported in previous WM experiments. These results show that humans have a large-capacity temporary memory store in the absence of proactive interference, and raise the question of whether temporary memory in everyday cognitive processing is severely limited as in WM experiments, or has the much larger capacity found in the present experiments. PMID:23937181

  10. Age-dependent capacity to accelerate protein synthesis dictates the extent of compensatory growth in skeletal muscle following undernutrition

    USDA-ARS?s Scientific Manuscript database

    In both humans and animals, impaired growth during early life compromises adult lean body mass and muscle strength despite skeletal muscle’s large regenerative capacity. To identify the significance of developmental age on skeletal muscle’s capacity for catch-up growth following an episode of under ...

  11. Passengers of Impaired Drivers

    PubMed Central

    Romano, Eduardo; Kelley-Baker, Tara; Lacey, John

    2012-01-01

    Introduction The aims of this study are (a) to estimate the prevalence of passengers riding with alcohol-impaired drivers; (b) to investigate the role of demographic factors (age, gender, race/ethnicity, educational status) and relevant driving conditions (time of the day, trip origin, vehicle ownership) on shaping the likelihood of alcohol-impaired driving; (c) to identify and estimate the prevalence of passengers as alternative drivers (PADs); and (d) to examine the role that vehicle ownership plays in shaping the occurrence of PADs. Method Data came from a unique convenience sample of passengers obtained from the 2007 National Roadside Survey, a random sample of drivers from the 48 contiguous states. Results The prevalence of PADs in the targeted population (mostly weekend night vehicles) was higher with drivers at .00

  12. Fertility impairment in radiotherapy

    PubMed Central

    Kuźba-Kryszak, Tamara; Nowikiewicz, Tomasz; Żyromska, Agnieszka

    2016-01-01

    Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning. PMID:27647982

  13. Testamentary capacity and guardianship assessments.

    PubMed

    Roof, Jason G

    2012-12-01

    This article discusses the ever-increasing opportunity for forensic mental health evaluators to provide assistance to the legal system in the areas of testamentary capacity and guardianship assessments. These areas of evaluation are defined, and a discussion of preparation and execution of effective evaluations is provided. The legal concepts of undue influence and insane delusion are defined and applied to the evaluator's interview. Common cognitive concerns such as dementia and delirium may affect an evaluee's capacity, and their presence and effect on the evaluee are considered. Evaluators are encouraged to carefully consider specific capacities related to the relevant legal questions posed. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. A California generation capacity market

    SciTech Connect

    Conkling, R.L.

    1998-10-01

    California, overconfident with its new Power Exchange spot market, seems unaware that it could be afflicted by the same turmoil that bludgeoned the Midwest in June. An electricity capacity market should be put in place before crisis strikes. This article outlines a framework for adding an electricity capacity market in California. The new market would not create a new bureaucracy but would function within the state`s now operational PX and independent system operator (ISO) mechanisms. It would be an open market, in which capacity would be traded transparently, with freedom of entree for all willing sellers and all willing buyers.

  15. Guideline of the Korean Academy of Medical Sciences for Assessing Respiratory Impairment

    PubMed Central

    Kim, HoJoong; Lee, Kye Young; Kim, Joung Taek

    2009-01-01

    The presently used impairment rating guidelines in Korea do not accurately reflect the injury in various lung diseases. Therefore, they need to be made more objective and quantitative with new measurements, using indicators to more precisely represent impairment in the major respiratory diseases. We develop a respiratory impairment rating guideline to ensure that the same grade or impairment rating would be obtained regardless of surgeons who determinate it. Specialists in respiratory medicine and thoracic surgeons determined the impairment grades. Moreover, the impairment should be irreversible for more than 6 months. The impairment rating depends on the level of forced vital capacity, forced expiratory volume 1 second, diffusion capacity of carbon monoxide, arterial oxygen pressure, and arterial carbon dioxide pressure. The degree of whole body impairment is defined by each grade: first 81-95%, second 66-80%, third 51-65%, fourth 36-50%, and fifth 21-35%. In conclusion, we develop a respiratory impairment rating guideline for Koreans. Any qualified specialist can easily use it and judge objective scoring. PMID:19503683

  16. Guideline of the Korean Academy of Medical Sciences for assessing respiratory impairment.

    PubMed

    Kim, HoJoong; Lee, Kye Young; Kim, Joung Taek; Uh, Soo-taek

    2009-05-01

    The presently used impairment rating guidelines in Korea do not accurately reflect the injury in various lung diseases. Therefore, they need to be made more objective and quantitative with new measurements, using indicators to more precisely represent impairment in the major respiratory diseases. We develop a respiratory impairment rating guideline to ensure that the same grade or impairment rating would be obtained regardless of surgeons who determinate it. Specialists in respiratory medicine and thoracic surgeons determined the impairment grades. Moreover, the impairment should be irreversible for more than 6 months. The impairment rating depends on the level of forced vital capacity, forced expiratory volume 1 second, diffusion capacity of carbon monoxide, arterial oxygen pressure, and arterial carbon dioxide pressure. The degree of whole body impairment is defined by each grade: first 81-95%, second 66-80%, third 51-65%, fourth 36-50%, and fifth 21-35%. In conclusion, we develop a respiratory impairment rating guideline for Koreans. Any qualified specialist can easily use it and judge objective scoring.

  17. To build capacity, build confidence

    NASA Astrophysics Data System (ADS)

    Hewitson, Bruce

    2015-07-01

    The history of attempts to spread scientific know-how beyond western centres of excellence is littered with failures. Capacity building needs long-term commitment, a critical mass of trainees, and a supportive home environment.

  18. Savannah Capacity Building Pilot Project

    EPA Pesticide Factsheets

    A series of meetings involving the Georgia Ports Authority and near-port community organizations were convened for a community capacity building pilot project. Technical assistance is being provided by EPA to support effective engagement.

  19. Capacity Markets and Market Stability

    SciTech Connect

    Stauffer, Hoff

    2006-04-15

    The good news is that market stability can be achieved through a combination of longer-term contracts, auctions for far enough in the future to permit new entry, a capacity management system, and a demand curve. The bad news is that if and when stable capacity markets are designed, the markets may seem to be relatively close to where we started - with integrated resource planning. Market ideologues will find this anathema. (author)

  20. Maximizing the optical network capacity

    PubMed Central

    Bayvel, Polina; Maher, Robert; Liga, Gabriele; Shevchenko, Nikita A.; Lavery, Domaniç; Killey, Robert I.

    2016-01-01

    Most of the digital data transmitted are carried by optical fibres, forming the great part of the national and international communication infrastructure. The information-carrying capacity of these networks has increased vastly over the past decades through the introduction of wavelength division multiplexing, advanced modulation formats, digital signal processing and improved optical fibre and amplifier technology. These developments sparked the communication revolution and the growth of the Internet, and have created an illusion of infinite capacity being available. But as the volume of data continues to increase, is there a limit to the capacity of an optical fibre communication channel? The optical fibre channel is nonlinear, and the intensity-dependent Kerr nonlinearity limit has been suggested as a fundamental limit to optical fibre capacity. Current research is focused on whether this is the case, and on linear and nonlinear techniques, both optical and electronic, to understand, unlock and maximize the capacity of optical communications in the nonlinear regime. This paper describes some of them and discusses future prospects for success in the quest for capacity. PMID:26809572

  1. The physical performance test predicts aerobic capacity sufficient for independence in early-stage Alzheimer disease.

    PubMed

    Vidoni, Eric D; Billinger, Sandra A; Lee, Charesa; Hamilton, Jenna; Burns, Jeffrey M

    2012-01-01

    Early identification of physical impairment related to Alzheimer disease (AD) is increasingly identified as an important aspect of diagnosis and care. Clinically accessible tools for evaluating physical capacity and impairment in AD have been developed but require further characterization for their effective use. To assess the utility of the Physical Performance Test (PPT) for identifying functionally limiting aerobic capacity in older adults with AD and without dementia. Secondary analysis of a dataset of community dwelling older adults, 70 without dementia and 60 with early-stage AD. Participants were administered the PPT and performed a graded maximal exercise test. The clinical utility of 2 versions of the PPT was described by determining sensitivity and specificity to functionally limiting aerobic capacity. The 9-item PPT is predictive of diminished aerobic capacity in older adults with AD. A score of 28 or less indicates likelihood of functionally limiting aerobic capacity that would limit independent function with 67% sensitivity and 67% specificity. The 4-item mini-PPT demonstrates improved capability for identifying impaired functional aerobic capacity with 85% sensitivity and 62% specificity. The PPT was not useful for identifying impaired functional aerobic capacity in older adults without dementia. The PPT, which incorporates basic and instrumental activities of daily living as test items, and the mini-PPT which focuses on basic activities of daily living and simple physical functions, are both clinically useful tool for the evaluation for individuals in the earliest stages of AD and both provide important information about functional performance. The mini-PPT additionally inform the clinician as to whether or not individual with early-stage AD is likely to have insufficient aerobic capacity to perform instrumental daily functions.

  2. Impairments in Skin Integrity.

    PubMed

    Murphree, Rose W

    2017-09-01

    Altered skin integrity increases the chance of infection, impaired mobility, and decreased function and may result in the loss of limb or, sometimes, life. Skin is affected by both intrinsic and extrinsic factors. Intrinsic factors can include altered nutritional status, vascular disease issues, and diabetes. Extrinsic factors include falls, accidents, pressure, immobility, and surgical procedures. Ensuring skin integrity in the elderly requires a team approach and includes the individual, caregivers, and clinicians. The twenty-first century clinician has several online, evidence-based tools to assist with optimal treatment plans. Understanding best practices in addressing skin integrity issues can promote positive outcomes with the elderly. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Category specific semantic impairments.

    PubMed

    Warrington, E K; Shallice, T

    1984-09-01

    We report a quantitative investigation of the visual identification and auditory comprehension deficits of 4 patients who had made a partial recovery from herpes simplex encephalitis. Clinical observations had suggested the selective impairment and selective preservation of certain categories of visual stimuli. In all 4 patients a significant discrepancy between their ability to identify inanimate objects and inability to identify living things and foods was demonstrated. In 2 patients it was possible to compare visual and verbal modalities and the same pattern of dissociation was observed in both. For 1 patient, comprehension of abstract words was significantly superior to comprehension of concrete words. Consistency of responses was recorded within a modality in contrast to a much lesser degree of consistency between modalities. We interpret our findings in terms of category specificity in the organization of meaning systems that are also modality specific semantic systems.

  4. Informed consent procedures with cognitively impaired patients: A review of ethics and best practices.

    PubMed

    Fields, Lindy Marie; Calvert, James Douglas

    2015-08-01

    The objectives of this article are to discuss ethical issues of informed consent in cognitively impaired patients and review considerations for capacity determination. We will also discuss how to evaluate capacity, determine competence, and obtain informed consent when a patient is deemed incompetent. This review emphasizes how to carry out informed consent procedures when capacity is questionable and discusses measures supported for use when determining cognitively impaired patients' ability to consent. Information was gathered from medical and psychological codes of ethics, peer-reviewed journals, published guidelines from health-care organizations (e.g., American Medical Association), and scholarly books. Google Scholar and PsycINFO were searched for articles related to 'informed consent' and 'cognitive impairment' published in English between 1975 and 2014. Relevant sources referenced in retrieved publications were subsequently searched and reviewed. We selected 49 sources generated by our search. Sources were included in our review if they presented information related to at least one of our focus areas. These areas included: review of informed consent ethics and procedures, review of cognitive impairment evaluations, recommendations for measuring cognitive capacity, and alternative forms of informed consent. Patients' cognitive impairments can hinder the ability of patients to understand treatment options. Evaluating the capacity of patients with cognitive impairment to understand treatment options is vital for valid informed consent and should be guided by best practices. Thus, proper identification of patients with questionable capacity, capacity evaluation, and determination of competence, as well as reliance upon appropriate alternative consent procedures, are paramount. © 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.

  5. The effects of sleep loss on capacity and effort

    PubMed Central

    Engle-Friedman, Mindy

    2014-01-01

    Sleep loss appears to affect the capacity for performance and access to energetic resources. This paper reviews research examining the physical substrates referred to as resource capacity, the role of sleep in protecting that capacity and the reaction of the system as it attempts to respond with effort to overcome the limitations on capacity caused by sleep loss. Effort is the extent to which an organism will exert itself beyond basic levels of functioning or attempt alternative strategies to maintain performance. The purpose of this review is to bring together research across sleep disciplines to clarify the substrates that constitute and influence capacity for performance, consider how the loss of sleep influences access to those resources, examine cortical, physiological, perceptual, behavioral and subjective effort responses and consider how these responses reflect a system reacting to changes in the resource environment. When sleep deprived, the ability to perform tasks that require additional energy is impaired and the ability of the system to overcome the deficiencies caused by sleep loss is limited. Taking on tasks that require effort including school work, meal preparation, pulling off the road to nap when driving drowsy appear to be more challenging during sleep loss. Sleep loss impacts the effort-related choices we make and those choices may influence our health and safety. PMID:26483932

  6. Cognitive Impairment and Tramadol Dependence.

    PubMed

    Bassiony, Medhat M; Youssef, Usama M; Hassan, Mervat S; Salah El-Deen, Ghada M; El-Gohari, Hayam; Abdelghani, Mohamed; Abdalla, Ahmed; Ibrahim, Dalia H

    2017-02-01

    Cognitive impairment is one of the consequences of substance abuse. Tramadol abuse is a public health problem in Egypt. The objective of this study was to estimate the prevalence and correlates of cognitive impairment among tramadol-abuse patients and control subjects. This study included 100 patients with tramadol abuse and 100 control subjects (matched for age, sex, and education) who were recruited from Zagazig University Hospital, Egypt. Patients were divided into 2 groups: patients who used tramadol only (tramadol-alone group) and patients who used tramadol and other substances (polysubstance group). The participants were interviewed using Montreal Cognitive Assessment test and had urine screening for drugs. Twenty-four percent of the cases used tramadol alone, whereas the remaining used tramadol and other substances, mainly cannabis (66%) and benzodiazepines (27%). Tramadol-abuse patients were about 3 times more likely to have cognitive impairment than control subjects (81% vs 28%). Tramadol-alone patients were more than 2 times more likely to have cognitive impairment than control subjects (67% vs 28%). Cognitive impairment was significantly associated with polysubstance abuse. There was no association between cognitive impairment and sociodemographic or clinical factors. Cognitive impairment occurs commonly among tramadol-abuse patients. Memory impairment is the most common cognitive domain to be affected. There is a significant association between cognitive impairment and polysubstance abuse.

  7. [Multilingualism and specific language impairment].

    PubMed

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  8. Impaired Verb Fluency: A Sign of Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Ostberg, Per; Fernaeus, Sven-Erik; Hellstrom, Ake; Bogdanovic, Nenad; Wahlund, Lars Olof

    2005-01-01

    We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive…

  9. Impaired Verb Fluency: A Sign of Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Ostberg, Per; Fernaeus, Sven-Erik; Hellstrom, Ake; Bogdanovic, Nenad; Wahlund, Lars Olof

    2005-01-01

    We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive…

  10. Virtual Reality Functional Capacity Assessment In Schizophrenia: Preliminary Data Regarding Feasibility and Correlations with Cognitive and Functional Capacity Performance

    PubMed Central

    Ruse, Stacy A.; Harvey, Philip D.; Davis, Vicki G.; Atkins, Alexandra S.; Fox, Kolleen H.; Keefe, Richard S.E.

    2014-01-01

    Introduction Assessment of functional capacity is an intrinsic part of determining the functional relevance of response to treatment of cognitive impairment in schizophrenia. Existing methods are highly and consistently correlated with performance on neuropsychological tests, but most current assessments of functional capacity are still paper and pencil simulations. We developed a computerized virtual reality assessment that contains all of the components of a shopping trip. Methods We administered the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) to 54 healthy controls and to 51 people with schizophrenia to test its feasibility. Dependent variables for the VRFCAT included time to completion and errors on 12 objectives and the number of times that an individual failed to complete an objective. The MATRICS Consensus Cognitive Battery (MCCB) and a standard functional capacity measure, the UCSD Performance-Based Skills Assessment-Brief (UPSA-B) were administered to the patients with schizophrenia. Results Patients with schizophrenia performed more poorly than healthy controls on 10/11 of the time variables, as well as 2/12 error scores and 2/12 failed objectives. Pearson correlations for 7 of 15 VRFCAT variables with MCCB composite scores were statistically significant. Conclusion These results provide support for the possibility of computerized functional capacity assessment, but more substantial studies are required. PMID:25083416

  11. Capacities of quantum amplifier channels

    NASA Astrophysics Data System (ADS)

    Qi, Haoyu; Wilde, Mark M.

    2017-01-01

    Quantum amplifier channels are at the core of several physical processes. Not only do they model the optical process of spontaneous parametric down-conversion, but the transformation corresponding to an amplifier channel also describes the physics of the dynamical Casimir effect in superconducting circuits, the Unruh effect, and Hawking radiation. Here we study the communication capabilities of quantum amplifier channels. Invoking a recently established minimum output-entropy theorem for single-mode phase-insensitive Gaussian channels, we determine capacities of quantum-limited amplifier channels in three different scenarios. First, we establish the capacities of quantum-limited amplifier channels for one of the most general communication tasks, characterized by the trade-off between classical communication, quantum communication, and entanglement generation or consumption. Second, we establish capacities of quantum-limited amplifier channels for the trade-off between public classical communication, private classical communication, and secret key generation. Third, we determine the capacity region for a broadcast channel induced by the quantum-limited amplifier channel, and we also show that a fully quantum strategy outperforms those achieved by classical coherent-detection strategies. In all three scenarios, we find that the capacities significantly outperform communication rates achieved with a naive time-sharing strategy.

  12. Heat capacities of aluminum clusters

    NASA Astrophysics Data System (ADS)

    Starace, Anne; Cao, Baopeng; Judd, Oscar; Jarrold, Martin

    2009-03-01

    Clusters of certain elements are known to undergo phase transitions from solid-like to liquid-like states. Aluminum clusters have emerged as a model system for metal cluster phase transitions [1]. We report here the measurement of heat capacities of cationic clusters containing 84 to 127 Al atoms using a multi-collision induced dissociation mass spectrometry method [2]. We find two major changes in the heat capacities with increasing cluster size: (1) the fluctuations in the temperature of the phase transition vary more smoothly and (2) the peaks in heat capacity become sharper. Furthermore, we have found a range of cluster sizes (115-117 atoms) that contain two distinct peaks, separated by baseline, in their heat capacities. The origin of the extra peaks in the heat capacity, which is suspected to be due either to a pre-melting transition or to a solid-to-solid transition prior to the melting transition, will be further investigated by means of annealing experiments. The current work extends prior work on singly charged Al cluster cations having 16-83 atoms [2, 3]. [1] Breaux, G. A.; Neal, C. M.; Cao, B.; Jarrold, M. F. Physical Review Letters 2005, 94. [2] Neal, C. M.; Starace, A. K.; Jarrold, M. F. Journal of the American Society for Mass Spectrometry 2007, 18, 74-81. [3] Neal, C. M.; Starace, A. K.; Jarrold, M. F. Physical Review B 2007, 76. [4] This work is supported by NSF.

  13. [Neuropsychological impairment in the early Alzheimer's disease].

    PubMed

    Traykov, L; Rigaud, A-S; Cesaro, P; Boller, F

    2007-01-01

    This analysis is centered on the study of cognitive disorders in Alzheimer's disease (AD), mainly for major neuro-psychological functions. We insist on the heterogeneity of the clinical picture peculiarly in the early stages of the illness, even if the deficits of episodic memory and of attentional/executive capacities are the first to deteriorate, preceding impairment in perceptual and language function and potentially having a substantial impact on the patient's capacity to cope independently. An episodic memory deficit is the hallmark of AD, but it must be stressed that this deficit may take different forms and its origin may be traced back to different cognitive mechanisms. One of the most striking aspects of episodic memory impairment in AD is the rapidity of forgetfulness on which screening and diagnostic tests of AD are based. There is some evidence that the episodic memory deficit in AD is one of learning (encoding and storage) of information rather than to a deficit of retrieval. Furthermore, episodic memory performance in AD depends on the integrity of semantic memory abilities, so giving support to a hierarchical model of organization of human memory. Finally, recent results show that an impairment of conscious recollection is responsible for the poor performance of AD patients in recognition memory. Executive deficits appear predominantly in tasks requiring cognitive flexibility and self-monitoring. With the progression of the disease, additional deficits are observed in the verbal concept formation abilities. These findings might be also very useful in the differential diagnosis between AD and the other cortical and subcortical dementias, as well as in the differentiation between AD and fronto-temporal dementia. We consider that studying early stages of the illness is necessary to delineate the diagnostic signs, to validate the new therapeutic experiments, to predict stages of decline. Recent research suggested that onset of AD is commonly preceded by

  14. Boomerang pillows and respiratory capacity.

    PubMed

    Roberts, K L; Brittin, M; Cook, M A; deClifford, J

    1994-05-01

    An experimental study was done to determine whether subjects placed on boomerang pillows would have lower vital capacities than subjects placed on straight pillows after 30 minutes. A sample of 42 subjects took part in the study in a nursing laboratory. A crossover design was used in which subjects were measured in both conditions. The findings indicated that there was no significant difference in the vital capacities of subjects in the two conditions. An associated finding was that the vital capacities were significantly lower in a semi-Fowler's position than in a straight chair. It was concluded that boomerang pillows are safe to use for persons without respiratory problems. Further research is needed into the effect of boomerang pillows on persons with respiratory deficits.

  15. On risk and decisional capacity.

    PubMed

    Checkland, D

    2001-02-01

    Limits to paternalism are, in the liberal democracies, partially defined by the concepts of decision-making capacity/incapacity (mental competence/incompetence). The paper is a response to Ian Wilks's (1997) recent attempt to defend the idea that the standards for decisional capacity ought to vary with the degree of risk incurred by certain choices. Wilks's defense is based on a direct appeal to the logical features of examples and analogies, thus attempting to by-pass earlier criticisms (e.g., Culver & Gert, 1990) of risk-based standards. Wilks's argument is found wanting on the grounds that he misconstrues the logic of such capacity, especially in accounting for conceptual and pragmatic ties with issues of decisional authority. A diagnosis is offered as to the source of Wilks's error (the assumption that mental competence is a species of wider genus of "competence"), and an alternative way of accounting for risk within the predominant contemporary legal framework is sketched.

  16. Computational Medical Apportionment Determination for Impairment Ratings

    NASA Astrophysics Data System (ADS)

    Artz, Jerry; Thompson, Marten; Alchemy, Md, John; Penn, Md, Daniel

    2017-01-01

    Unique computational techniques are used to calculate apportionment percentages for Whole Person Impairment (WPI) Ratings for workers with job-related injuries/illnesses. This interdisciplinary project includes collaboration among physicists, engineers, and concerned medical professionals. Medical providers are often asked to medically determine multiple contributing factors to disease states (e.g. diabetes, obesity, arthritis, and prior injury) in the context of personal injury as it pertains to permanent impairment. The process of making this determination is referred to as ``apportionment''. The economic value of apportionment is far reaching and represents a significant impact to all stakeholders in the injury resolution and settlement arena. The process of apportionment is necessary to assign monetary value for the stakeholders when an injury occurs. The ultimate trier-of-fact is the judicial system. The medical provider's role in this capacity is to apply known medical scientific knowledge and present it in a format that is objective and reproducible for the stakeholders. In this presentation the traditional challenges of apportionment will be outlined, and a novel approach creating mathematical bounding and modeling of pathology-weighted data sets will be presented.

  17. Rural research capacity building program: capacity building outcomes.

    PubMed

    Webster, Emma; Thomas, Margaret; Ong, Narelle; Cutler, Linda

    2011-01-01

    The Rural Research Capacity Building Program commenced in 2006 with the aim of developing research skills in rural health workers. The program was based on the capacity building principles of workforce development, organisational development, resource allocation, partnership and leadership. Qualitative methods were used to assess capacity building outcomes. A sample of candidates from the 2006 and 2007 cohorts were selected for interview using stratified random sampling and supplemental purposive sampling. Twenty-five individual semi-structured interviews were conducted with candidates, their managers and mentors. Interviews were thematically analysed. The program components of teaching, mentoring and networking led to the development of research skills in candidates undertaking the program. This workforce development resulted in workplace change, particularly where the candidate's project was 'close to practice' and they had management support. The leadership shown and partnerships developed by the program managers enhanced the workforce development and organisational change outcomes. Resources, such as backfill and incidentals, were useful for candidates, but practicalities, such as availability of replacement staff, limited effectiveness. This study showed the value of using a capacity building framework and demonstrated that undertaking research on a topic close to practice positioned candidates to drive change within their organisation.

  18. Buffer Capacity: An Undergraduate Laboratory Experiment.

    ERIC Educational Resources Information Center

    Russo, Steven O.; Hanania, George I. H.

    1987-01-01

    Describes a quantitative experiment designed to demonstrate buffer action and the measurement of buffer capacity. Discusses how to make acetate buffers, determine their buffer capacity, plot the capacity/pH curve, and interpret the data obtained. (TW)

  19. Buffer Capacity: An Undergraduate Laboratory Experiment.

    ERIC Educational Resources Information Center

    Russo, Steven O.; Hanania, George I. H.

    1987-01-01

    Describes a quantitative experiment designed to demonstrate buffer action and the measurement of buffer capacity. Discusses how to make acetate buffers, determine their buffer capacity, plot the capacity/pH curve, and interpret the data obtained. (TW)

  20. The visually impaired patient.

    PubMed

    Rosenberg, Eric A; Sperazza, Laura C

    2008-05-15

    Blindness or low vision affects more than 3 million Americans 40 years and older, and this number is projected to reach 5.5 million by 2020. In addition to treating a patient's vision loss and comorbid medical issues, physicians must be aware of the physical limitations and social issues associated with vision loss to optimize health and independent living for the visually impaired patient. In the United States, the four most prevalent etiologies of vision loss in persons 40 years and older are age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy. Exudative macular degeneration is treated with laser therapy, and progression of nonexudative macular degeneration in its advanced stages may be slowed with high-dose antioxidant and zinc regimens. The value of screening for glaucoma is uncertain; management of this condition relies on topical ocular medications. Cataract symptoms include decreased visual acuity, decreased color perception, decreased contrast sensitivity, and glare disability. Lifestyle and environmental interventions can improve function in patients with cataracts, but surgery is commonly performed if the condition worsens. Diabetic retinopathy responds to tight glucose control, and severe cases marked by macular edema are treated with laser photocoagulation. Vision-enhancing devices can help magnify objects, and nonoptical interventions include special filters and enhanced lighting.

  1. VOT and hearing impairment

    NASA Astrophysics Data System (ADS)

    Lane, Harlan; Perkell, Joseph

    2001-05-01

    When deafened adults recover some hearing after receiving a cochlear implant, numerous changes in their speech occur at both phonemic and suprasegmental levels. If a change toward normative values is observed for some phonemic parameter, it may be attributed to the restored hearing; however, it may be a by-product of a suprasegmental change. Consistent with results reported for speakers with normal hearing, Lane et al. [J. Acoust. Soc. Am. 98, 3096-3106 (1995)] observed in implant users that VOT varies approximately linearly with syllable duration. Therefore, in comparing pre- and postimplant measures of VOT in five speakers, each token's VOT was adjusted for the change in syllable duration of that token relative to the mean syllable duration in a baseline session (called VOTc). Preimplant, the deaf speakers characteristically uttered plosives with abnormally short VOTc. With some hearing restored, four of the five lengthened VOTc. Changes in voiced plosives' VOTc with restored hearing were correlated with changes in SPL. Some of the reliable VOTc increases that were not correlated with SPL may have been caused by auditory validation of an internal model for phoneme production. Recent studies of VOT in hearing-impaired speakers will be reviewed in this light. [Work supported by NIDCD, NIH.

  2. Wills, testamentary capacity and undue influence.

    PubMed

    Peer, I N

    1981-01-01

    Psychiatrists are generally familiar with the issues involved in testamentary capacity, but not with the nuances involved in undue influence. The legal factors in determining undue influence where the will of one party is substituted or imposed on the testator have been reviewed. Most important are circumstances where the testator has some degree of mental impairment, where a person in a position of trust imposes his or her will on a testator and is a beneficiary in some way, where there are unusual circumstances in the disposition of property or where there are suspicious circumstances that raise such a question. In particular, a lawyer who prepared a will in which he is a beneficiary will be vulnerable to a charge of undue influence. Examples of actual occurrences have been presented. They illustrate the fact that psychiatric evaluation may be most important in determining the validity of a will even where there is no finding of testamentary incapacity. In such cases, the psychiatric or other medical information is only one factor to be considered by the judge along with the other elements to be considered by the court. Undue influence is therefore another area of the law about which forensic psychiatrists should be familiar and knowledgeable. Hopefully, this review will serve that purpose.

  3. Superadditivity of classical capacity revisited

    SciTech Connect

    Pilyavets, Oleg V.; Karpov, Evgueni A.; Schäfer, Joachim

    2014-12-04

    We introduce new type of superadditivity for classical capacity of quantum channels, which involves the properties of channels’ environment. By imposing different restrictions on the total energy contained in channels’ environment we can consider different types of superadditivity. Using lossy bosonic and additive noise quantum channels as examples, we demonstrate that their capacities can be either additive or superadditive depending on the values of channels parameters. The parameters corresponding to transition between the additive and superadditive cases are related with recently found critical and supercritical parameters for Gaussian channels.

  4. Free Energy and Heat Capacity

    SciTech Connect

    Kurata, Masaki; Devanathan, Ramaswami

    2015-10-13

    Free energy and heat capacity of actinide elements and compounds are important properties for the evaluation of the safety and reliable performance of nuclear fuel. They are essential inputs for models that describe complex phenomena that govern the behaviour of actinide compounds during nuclear fuel fabrication and irradiation. This chapter introduces various experimental methods to measure free energy and heat capacity to serve as inputs for models and to validate computer simulations. This is followed by a discussion of computer simulation of these properties, and recent simulations of thermophysical properties of nuclear fuel are briefly reviewed.

  5. The Capacity Profile: A Method to Classify Additional Care Needs in Children with Neurodevelopmental Disabilities

    ERIC Educational Resources Information Center

    Meester-Delver, Anke; Beelen, Anita; Hennekam, Raoul; Nollet, Frans; Hadders-Algra, Mijna

    2007-01-01

    The aim of this study was to determine the interrater reliability and stability over time of the Capacity Profile (CAP). The CAP is a standardized method for classifying additional care needs indicated by current impairments in five domains of body functions: physical health, neuromusculoskeletal and movement-related, sensory, mental, and voice…

  6. The Capacity Profile: A Method to Classify Additional Care Needs in Children with Neurodevelopmental Disabilities

    ERIC Educational Resources Information Center

    Meester-Delver, Anke; Beelen, Anita; Hennekam, Raoul; Nollet, Frans; Hadders-Algra, Mijna

    2007-01-01

    The aim of this study was to determine the interrater reliability and stability over time of the Capacity Profile (CAP). The CAP is a standardized method for classifying additional care needs indicated by current impairments in five domains of body functions: physical health, neuromusculoskeletal and movement-related, sensory, mental, and voice…

  7. Building Capacity for Sustained Improvement.

    ERIC Educational Resources Information Center

    Digate, Gail A.; Rhodes, Lewis A.

    1995-01-01

    Since 1990, over 40 Illinois and Massachusetts school districts have built capacity for sustained improvement through vertically structured, district-level Learning Leadership Teams. Originated by Motorola executives, LLT was based on an understanding of organizational change derived from the National Science Foundation's definition of systemic…

  8. Endoscopic capacity in West Africa.

    PubMed

    Perl, Daniel; Leddin, Desmond; Bizos, Damon; Veitch, Andrew; N'Dow, James; Bush-Goddard, Stephanie; Njie, Ramou; Lemoine, Maud; Anderson, Suzanne T; Igoe, John; Anandasabapathy, Sharmila; Shah, Brijen

    2016-03-01

    Levels of endoscopic demand and capacity in West Africa are unclear. This paper aims to: 1. describe the current labor and endoscopic capacity, 2. quantify the impact of a mixed-methods endoscopy course on healthcare professionals in West Africa, and 3. quantify the types of diagnoses encountered. In a three-day course, healthcare professionals were surveyed on endoscopic resources and capacity and were taught through active observation of live cases, case discussion, simulator experience and didactics. Before and after didactics, multiple-choice exams as well as questionnaires were administered to assess for course efficacy. Also, a case series of 23 patients needing upper GI endoscopy was done. In surveying physicians, less than half had resources to perform an EGD and none could perform an ERCP, while waiting time for emergency endoscopy in urban populations was at least one day. In assessing improvement in medical knowledge among participants after didactics, objective data paired with subjective responses was more useful than either alone. Of 23 patients who received endoscopy, 7 required endoscopic intervention with 6 having gastric or esophageal varices. Currently the endoscopic capacity in West Africa is not sufficient. A formal GI course with simulation and didactics improves gastrointestinal knowledge amongst participants.

  9. Building Capacity and Sustaining Endeavors

    ERIC Educational Resources Information Center

    Kraybill, Anne; Din, Herminia

    2015-01-01

    In this article, institutional capacity and sustainability is considered. The authors explore a case study from Crystal Bridges Museum of American Art as an example of how museums can leverage not only online technologies to reach more learners regardless of geography, but to increase their reach through strategic partnerships.

  10. North American fertilizer capacity data

    SciTech Connect

    Not Available

    1991-12-01

    This listing of producers and their fertilizer production capacities was compiled in October 1991 with the cooperation of the US and Canadian fertilizer industry. Fertilizers production is reported or forecasted for the years 1987 through 1997. The fertilizers reported on are: ammonia, ammonium nitrate, nitrogen solutions, urea, phosphate rock, wet-process phosphoric acid, ammonium phosphates, concentrated superphosphates, and potash.

  11. [Fasting and physical endurance capacity].

    PubMed

    Schürch, P M

    1993-03-01

    Fasting, or zero calorie diets are used not only by overweight people as a means of losing weight, but by athletes too. Their use is then explained on philosophical grounds, with the aim of even enhancing sports performance. The purpose of this investigation consisted of quantifying the effects of a 10-day fast on maximum performance capacity and endurance (as measured on a bicycle ergometer) of 12 female students of physical education of normal weight. The measurements included resting and exercise metabolism determinants, as well as weight and lean body mass. The main results show that after the diet period the maximum ergometric performance was lower in absolute terms as well as in relation to weight or lean body mass. Performance capacity for submaximal exercise was also reduced. Fat combustion was enhanced both at rest and during exercise. The reduction of maximum performance and endurance capacity may be explained by an enhanced muscle breakdown, an efficiency drop of muscular work, and an inadequate glycogen content of the acting muscles. Shorter fasting periods of 24-36 hours also lead to a lower performance level for exercise bouts extending from several minutes to 1-3 hours. An enhancement of fat combustion was always conspicuous. One may conclude that optimal physical performance is dependent on full hepatic and muscle glycogen stores. Glycogen concentration in the liver decreases sharply as a matter of fact after merely one day of carbohydrate shortage. Zero calorie or low carbohydrate diets are thus at variance with an optimal physical work capacity.

  12. AccessSTEM: Building Capacity

    ERIC Educational Resources Information Center

    DO-IT, 2009

    2009-01-01

    A series of activities were undertaken to understand the underrepresentation of people with disabilities in science, technology, engineering, and mathematics (STEM) careers and increase their participation in these fields. "AccessSTEM" collaborated with key stakeholders to conduct a "Capacity-Building Institute"…

  13. Building Capacity and Sustaining Endeavors

    ERIC Educational Resources Information Center

    Kraybill, Anne; Din, Herminia

    2015-01-01

    In this article, institutional capacity and sustainability is considered. The authors explore a case study from Crystal Bridges Museum of American Art as an example of how museums can leverage not only online technologies to reach more learners regardless of geography, but to increase their reach through strategic partnerships.

  14. North American fertilizer capacity data

    SciTech Connect

    Not Available

    1991-12-01

    This listing of producers and their fertilizer production capacities was compiled in October 1991 with the cooperation of the US and Canadian fertilizer industries. Yearly production and forecasts are given for 1987 through 1997. Fertilizers reported on include: ammonium sulfate, nitric acid, wet-process superphosphoric acid, normal superphosphate, elemental phosphorus, potassium sulfate, and sulfate of potash/magnesia.

  15. Capacity Issue Looms for Vouchers

    ERIC Educational Resources Information Center

    Zehr, Mary Ann

    2011-01-01

    State-level momentum in support of vouchers and tax credits that help students go to private schools highlights what has been a largely theoretical issue: private school capacity to support voucher-financed enrollment. Academics say the national supply of seats in secular and religious private schools is sufficient to meet short-term demand from…

  16. Effect of risk factors on exercise capacity in NIDDM.

    PubMed

    Estacio, R O; Wolfel, E E; Regensteiner, J G; Jeffers, B; Havranek, E P; Savage, S; Schrier, R W

    1996-01-01

    Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It is known that diabetic patients have an impaired exercise capacity when compared with nondiabetic age-matched control subjects, but the risk factors associated with this impairment have not been thoroughly analyzed. A total of 453 male and female NIDDM patients who underwent graded exercise testing with expired gas analysis were studied to determine the possible influences of demographic and cardiac risk factors on exercise capacity. Univariate and multiple linear regression analyses were performed on baseline patient characteristics with respect to peak oxygen consumption (VO2). In the regression analyses, African-American race was strongly associated with a decrease in peak VO2; the difference in means between African-Americans and other subjects for men was -2.50 ml.kg-1.min-1 (-4.28, -0.07, 95% CI) (P < 0.006) and for women was -2.96 ml.kg-1.min-1 (-4.45, -1.47) (P < 0.0002). Univariate analyses revealed that African-American subjects had increased prevalence, longer duration, and higher systolic and diastolic hypertension than the non-Hispanic and Hispanic whites. Other independent predictors of peak VO2 (reported as change in peak VO2 in milliliters per kilogram per minute) were BMI (men: -0.39 kg/m2 [-0.52, -0.29], P < 0.0001; women: -0.39 kg/m2 [-0.48, -0.31], P < 0.0001), age (men: -0.16/year [-0.23, -0.09], P < 0.0001; women: -0.17/year [-0.24, -0.11], P < 0.0001), baseline resting systolic blood pressure (men: -0.03/mmHg [-0.06, -0.01], P < 0.05; women: -0.03/mmHg (-0.06, -0.01)f1p4< 0.05), and pack-years smoking (men: -0.04/pack-years [-0.04, -0.01], P < 0.01; women: -0.04/pack-years [-0.07, -0.01], P < 0.0001). Thus, in this large NIDDM study, weight loss, smoking cessation, and aggressive blood pressure control, particularly in African-Americans with NIDDM, would appear to be important in improving exercise capacity and potentially improving the

  17. Phenotypic cognitive impairment in late-onset delusional disorder.

    PubMed

    Harris, Ben S; Kotsopoulos, Eleftheria J; Yamin, Sami

    2014-06-01

    Previous use of heterogeneous diagnostic criteria and insensitive cognitive measures has impeded clarification of the extent and type of cognitive impairment specific to late-onset delusional disorder. We examined whether clinical presentations of late-onset delusional disorder are associated with prodromal or established dementia, and whether it might be a discrete clinical syndrome characterized by its own profile of cognitive impairment. Nineteen patients with late-onset delusional disorder from a hospital psychiatric service and 20 patients with dementia of the Alzheimer's type (AD) from an outpatient memory clinic were recruited in a consecutive case series. All patients underwent comprehensive neuropsychological assessment that included general intellectual function, executive function, new learning and delayed memory, language, processing speed, and visuo-perceptual skills. Late-onset delusional disorder patients showed moderate impairment to conceptual reasoning, visual object recognition, processing speed, and confrontation naming. Severe impairment appeared in visuo-perceptual planning and organization, and divided attention. Compared with the Alzheimer's disease (AD) group, the late-onset delusional disorder group demonstrated significantly poorer visuo-perceptual skills but a significantly better capacity to consolidate information into delayed memory. A high rate of marked cognitive impairment occurs in late-onset delusional disorder. There was evidence of a conceptual reasoning deficit, plus the presence of a visuo-perceptual impairment affecting object recognition. This impairment profile can explain the genesis and maintenance of the observed delusions. Understanding late-onset delusional disorder as other than a purely psychiatric phenomenon or a precursor to AD will lead to better assessment and management approaches.

  18. Forced vital capacity, slow vital capacity, or inspiratory vital capacity: which is the best measure of vital capacity?

    PubMed

    Chhabra, S K

    1998-01-01

    Vital capacity can be measured as forced vital capacity (FVC), slow vital capacity (SVC), and inspiratory vital capacity (IVC). Although it is well known that the latter two are generally greater, a systematic comparison of the three in subjects with different degrees of airways obstruction has not been made. Sixty asthmatics and 20 normal subjects performed maneuvers for measurement of FVC, SVC, and IVC on a dry, rolling-seal spirometer. The severity of airways obstruction in asthmatics was classified as mild, moderate, and severe. There was no significant difference between FVC, SVC, and IVC in normal subjects. However, the three measurements of vital capacity were significantly different in all subgroups of asthmatics. FVC was smaller than both SVC and IVC. The differences were more marked in patients with moderate and severe degrees of airways obstruction. The differences between SVC and IVC were small and clinically not important. Forced expiratory volume in 1 sec (FEV1) expressed as percent of FVC, SVC, and IVC, was not different in normals and asthmatics with mild airways obstruction. The ratios were significantly different in asthmatics with moderate and severe airways obstruction. FEV1/IVC ratio was the lowest in both the groups followed by FEV1/SVC and FEV1/FVC. IVC and SVC are greater than FVC in patients with airways obstruction. This difference increases as the degree of obstruction increases. The difference between SVC or IVC and FVC serves as an indicator of air trapping. Both FVC and IVC could be measured and the largest VC used to calculate the FEV1/VC ratio because this increases the sensitivity of spirometry in detecting airways obstruction.

  19. Vascular cognitive impairment and dementia

    PubMed Central

    Gorelick, Philip B.; Counts, Scott E.; Nyenhuis, David

    2016-01-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer’s disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification.1 PMID:26704177

  20. Neurocognitive impairments in hiv infection.

    PubMed

    Edwin, T; Nammalvar, N; Sabhesan, S; Ganesh, R; Devarajan, H

    1999-01-01

    Neuropsychological impairments punctuate the early neurological involvement among HIV-1 infected patients. Three groups of patients, twenty in each were selected. The first group consisted of seronegative local controls, the second being a group of asymptomatic seropositive patients and the third a group of seropositive symptomatic individuals. All these three groups were tested using standard neuropsychological tests. Results indicate that a broad spectrum of impairments occur in the seropositive patients and that the impairments of various functions occur at different phases of the illness. The importance of these findings in prediction of early neurological disturbance is highlighted and their significance in the total management and rehabilitation is discussed.

  1. The Effect of Supercharger Capacity on Engine and Airplane Performance

    NASA Technical Reports Server (NTRS)

    Schey, O W; Gove, W D

    1930-01-01

    This report presents the results of an investigation to determine the effect of different supercharger capacities on the performance of an airplane and its engine . The tests were conducted on a DH4-M2 airplane powered with a Liberty 12 engine. In this investigation four supercharger capacities, obtained by driving a roots type supercharger at 1.615, 1.957, 2.4, and 3 time engine speed, were used to maintain sea-level pressure at the carburetor to altitudes of 7,000, 11,500, 17,000, and 22,000 feet, respectively. The performance of the airplane in climb and in level flight was determined for each of the four supercharger drive ratios and for the unsupercharged condition. The engine power was measured during these tests by means of a calibrated propeller. It was found that very little sacrifice in sea-level performance was experienced with the larger supercharger drive ratios as compared with performance obtained when using the smaller drive ratios. The results indicate that further increase in supercharger capacity over that obtained when using 3:1 drive ratio would give a slight increase in ceiling and in high-altitude performance but would considerably impair the performance for an appreciable distance below the critical altitude. As the supercharger capacity was increased, the height at which sea-level high speeds could be equaled or improved became a larger percentage of the maximum height of operation of the airplane.

  2. Exercise capacity following pediatric heart transplantation: A systematic review.

    PubMed

    Peterson, Sara; Su, Jennifer A; Szmuszkovicz, Jacqueline R; Johnson, Robert; Sargent, Barbara

    2017-08-01

    Pediatric HTs account for 13% of all HTs with >60% of recipients surviving at least 10 years post-HT. The purpose of this systematic review is to synthesize the literature on exercise capacity of pediatric HT recipients to improve understanding of the mechanisms that may explain the decreased exercise capacity. Six databases were searched for studies that compared the exercise capacity of HT recipients ≤21 years old with a control group or normative data. Sixteen studies were included. Pediatric HT recipients, as compared to controls or normative data, exhibit significantly higher resting HR, and at peak exercise exhibit significantly decreased HR, VO2 , power, work, minute ventilation, and exercise duration. Peak VO2 appears to improve within the first 2.5 years post-HT; peak work remains constant; and there is inconclusive evidence that peak HR, HR recovery, and HR reserve improve with time since HT. These results are discussed in the context of the mechanisms that may explain the impaired exercise capacity of pediatric HT recipients, including chronotropic incompetence, graft dysfunction, side effects of immunosuppression therapy, and deconditioning. In addition, the limited literature on rehabilitation after pediatric HT is summarized. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Unreasonable reasons: normative judgements in the assessment of mental capacity.

    PubMed

    Banner, Natalie F

    2012-10-01

    The recent Mental Capacity Act (2005) sets out a test for assessing a person's capacity to make treatment choices. In some cases, particularly in psychiatry, it is unclear how the criteria ought to be interpreted and applied by clinicians. In this paper, I argue that this uncertainty arises because the concept of capacity employed in the Act, and the diagnostic tools developed to assist its assessment, overlook the inherent normativity of judgements made about whether a person is using or weighing information in the decision-making process. Patients may fail on this criterion to the extent that they do not appear to be handling the information given in an appropriate way, on account of a mental impairment disrupting the way the decision process ought to proceed. Using case law and clinical examples, I describe some of the normative dimensions along which judgements of incapacity can be made, namely epistemic, evaluative and affective dimensions. Such judgements are complex and the normative standards by which a clinician may determine capacity cannot be reduced to a set of criteria. Rather, in recognizing this normativity, clinicians may better understand how clinical judgements are structured and what kinds of assumption may inform their assessment.

  4. Specific Language Impairment in Families: Evidence for Co-Occurrence with Reading Impairments.

    ERIC Educational Resources Information Center

    Flax, Judy F.; Realpe-Bonilla, Teresa; Hirsch, Linda S.; Brzustowicz, Linda M.; Bartlett, Christopher W.; Tallal, Paula

    2003-01-01

    Two family aggregation studies involving 25 children (ages 5-10) with specific language impairment (SLI) report the occurrence and co-occurrence of oral language impairments and reading impairments. Results indicate that when language impairments occur within families of SLI probands, these impairments generally co-occur with reading impairments.…

  5. Enhancing mobile phones for people with visual impairments through haptic icons: the effect of learning processes.

    PubMed

    Galdón, Pedro Maria; Madrid, R Ignacio; De La Rubia-Cuestas, Ernesto J; Diaz-Estrella, Antonio; Gonzalez, Lourdes

    2013-01-01

    We report the results of a study on the learnability ofhaptic icons used in a system for incoming-call identification in mobile phones. The aim was to explore the feasibility of using haptic icons to create new assistive technologies for people with visual impairments. We compared the performance and satisfaction of users with different visual capacities (visually impaired vs. sighted) and using different learning processes (unimodal vs. multimodal). A better recognition rate and user experience were observed for the visually impaired than for sighted users and for multimodal rather than unimodal learning processes.

  6. 303(d) Listed Impaired Waters

    EPA Pesticide Factsheets

    Geospatial data for 303(d) Impaired Waters are available as prepackaged national downloads or as GIS web and and data services. EPA provides geospatial data in the formats: GIS compatible shapefiles and geodatabases and ESRI and OGC web mapping.

  7. Genetic Counseling in Hearing Impairment.

    ERIC Educational Resources Information Center

    Fraser, George R.

    1979-01-01

    The problem of counseling is dealt with mainly in the context of severe hearing impairment, since moderate forms are often due to illness or other nongenetic factors and do not constitute a grave handicap. (DLS)

  8. Psychiatric Issues in Cognitive Impairment

    PubMed Central

    Aarsland, Dag; Taylor, John-Paul; Weintraub, Daniel

    2015-01-01

    Neuropsychiatric symptoms (NPS) such as depression, hallucinations and apathy commonly occur in Parkinson’s disease (PD) and have major clinical consequences including a negative impact on quality of life. This review discusses the epidemiology, clinical features, diagnostic procedures and treatment issues of NPS in PD and related disorders in the perspective of cognitive impairment, focusing on depression, anxiety, visual hallucinations, apathy, sleep disturbances, impulse control disorder and non-motor fluctuations. The majority of NPS are more common in PD patients with dementia, possibly related to shared underlying pathologies. Recent studies also suggest that NPS are associated with mild cognitive impairment in PD, in particular with the amnestic type. Accurate diagnosis of NPS is important but can be difficult, due to overlapping symptoms and similar appearance of symptoms of motor symptoms of parkinsonism, cognitive impairment, mood disorders and apathy. There are few systematic studies focusing on the management of NPS in PD with cognitive impairment. PMID:24757113

  9. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF... Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall be entitled to such Excess Capacity to integrate the operation of the Boulder City Area Projects and...

  10. Personality Disorders and Mindreading: Specific Impairments in Patients With Borderline Personality Disorder Compared to Other PDs.

    PubMed

    Semerari, Antonio; Colle, Livia; Pellecchia, Giovanni; Carcione, Antonino; Conti, Laura; Fiore, Donatella; Moroni, Fabio; Nicolò, Giuseppe; Procacci, Michele; Pedone, Roberto

    2015-08-01

    The capacity of understanding mental states is a complex function which involves several components. Single components can be selectively impaired in specific clinical populations. It has been suggested that impairments in mindreading are central for borderline personality disorder (BPD). However, empirical findings are inconsistent, and it is debatable whether BPD presents a specific profile of mindreading impairments. The aim of this study is to compare BPD and other PDs in mindreading. Seventy-two patients with BPD and 125 patients with other PD diagnoses were assessed using the Metacognition Assessment Interview. BPD showed difficulties in two mindreading functions, differentiation and integration, even when the severity of psychopathology was controlled. These results suggest a specific mindreading impairment in BPD and a strong relationship between these impairments and the severity of psychopathology.

  11. High capacity carbon dioxide sorbent

    DOEpatents

    Dietz, Steven Dean; Alptekin, Gokhan; Jayaraman, Ambalavanan

    2015-09-01

    The present invention provides a sorbent for the removal of carbon dioxide from gas streams, comprising: a CO.sub.2 capacity of at least 9 weight percent when measured at 22.degree. C. and 1 atmosphere; an H.sub.2O capacity of at most 15 weight percent when measured at 25.degree. C. and 1 atmosphere; and an isosteric heat of adsorption of from 5 to 8.5 kilocalories per mole of CO.sub.2. The invention also provides a carbon sorbent in a powder, a granular or a pellet form for the removal of carbon dioxide from gas streams, comprising: a carbon content of at least 90 weight percent; a nitrogen content of at least 1 weight percent; an oxygen content of at most 3 weight percent; a BET surface area from 50 to 2600 m.sup.2/g; and a DFT micropore volume from 0.04 to 0.8 cc/g.

  12. Cognitive Impairment Among the Aging Population in a Community in Southwest Nigeria.

    PubMed

    Adebiyi, Akindele O; Ogunniyi, Adesola; Adediran, Babatunde A; Olakehinde, Olaide O; Siwoku, Akeem A

    2016-04-01

    Vascular risk models can be quite informative in assisting the clinician to make a prediction of an individual's risk of cognitive impairment. Thus, a simple marker is a priority for low-capacity settings. This study examines the association of selected simple to deploy vascular markers with cognitive impairment in an elderly population. This cross-sectional study assessed the cognitive functions of older persons 65 years and older in southwest Nigeria. Vascular parameters and risk factors were also measured. Analysis was done using SPSS, and logistic regression was used to explore the association between cognitive impairment and certain vascular risk factors such as elevated blood pressure, diabetes, and pulse pressure. The study population comprised 623 participants (29.1% men) with mean age 73 ± 8.9 years. Having mean arterial pressure (MAP) and pulse pressure in the fourth quartiles (27% and 29.9%, respectively) was significantly associated with cognitive impairment (p= .001,p< .001). Predicted cardiovascular risks of 10% or more was significantly associated with cognitive impairment (p< .001). After adjusting for age, gender, educational level, and years of smoking, those with MAP in the fourth quartile were up to 3 times more likely to have cognitive impairment compared to those within the first quartile. Our study demonstrated that among elderly Nigerians, MAPs of 114 mmHg and more was an independent predictor of cognitive impairment. This is a simple measure that is available in low-capacity areas. © 2016 Society for Public Health Education.

  13. Physiologic Determinants of Exercise Capacity in Pulmonary Langerhans Cell Histiocytosis: A Multidimensional Analysis

    PubMed Central

    Fry, Stephanie; Giovannelli, Jonathan; Langlois, Carole; Bricout, Nicolas; Aguilaniu, Bernard; Bellocq, Agnes; Le Rouzic, Olivier; Dominique, Stephane; Delobbe, Alain; François, Geraldine; Tazi, Abdellatif; Wallaert, Benoit; Chenivesse, Cecile

    2017-01-01

    Background Reduced exercise capacity severely impacts quality of life in pulmonary Langerhans cell histiocytosis. Ascertaining mechanisms that impair exercise capacity is necessary to identify targets for symptomatic treatments. Methods Dyspnea, pulmonary function tests and cardiopulmonary exercise test were analysed in 62 study participants. Data were compared between subjects with impaired and normal aerobic capacity (V’O2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included V’O2 peak as the dependent variable and principal components as covariates. Results V’O2 peak was reduced in 44 subjects (71%). Subjects with impaired aerobic capacity presented: (i) decreased FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA and increased AaDO2, (ii) increased ventilatory equivalents at ventilatory threshold, VD/VT peak, AaDO2 peak and PaCO2 peak and decreased ventilatory reserve and PaO2 peak. There was no difference between groups in dyspnea scores. Principal component analysis extracted 4 principal components interpreted as follows: PC1: gas exchange; PC2: “pseudorestriction”; PC3: exercise-induced hyperpnea; PC4: air trapping. Multivariate analysis explained 65% of V’O2 peak. The 4 principal components were independently associated with V’O2 peak (βcoefficients: PC1: 9.3 [4.6; 14], PC2: 7.5 [3; 11.9], PC3: -5.3 [-9.6;-1.], PC4: -9.8 [-14,9;-4.7]). Conclusion Impaired exercise capacity is frequent in pulmonary Langerhans cell histiocytosis. It is mainly caused by pulmonary changes but is not associated with increased dyspnea intensity. Therefore, treating the lung represents a relevant approach for improving exercise capacity, even in patients experiencing mild dyspnea. PMID:28072848

  14. High capacity immobilized amine sorbents

    DOEpatents

    Gray, McMahan L.; Champagne, Kenneth J.; Soong, Yee; Filburn, Thomas

    2007-10-30

    A method is provided for making low-cost CO.sub.2 sorbents that can be used in large-scale gas-solid processes. The improved method entails treating an amine to increase the number of secondary amine groups and impregnating the amine in a porous solid support. The method increases the CO.sub.2 capture capacity and decreases the cost of utilizing an amine-enriched solid sorbent in CO.sub.2 capture systems.

  15. Capacity is the Wrong Paradigm

    DTIC Science & Technology

    2002-01-01

    Florida Gainesville, FL 32611-6120 ABSTRACT At present, \\capacity" is the prevailing paradigm for covert channels. With respect to steganography ...INTRODUCTION Steganography is the art and science of sending a hidden message from Alice to Bob, so that an eavesdropper is not aware that this hidden...discussed a di erent new paradigm con- cerning steganography . The concern of that new paradigm was \\when is something discovered." We feel that both

  16. Solubilisation capacity of Brij surfactants.

    PubMed

    Ribeiro, Maria E N P; de Moura, Carolina L; Vieira, Mariano G S; Gramosa, Nilce V; Chaibundit, Chiraphon; de Mattos, Marcos C; Attwood, David; Yeates, Stephen G; Nixon, S Keith; Ricardo, Nágila M P S

    2012-10-15

    The aim of this study was to investigate the potential of selected Brij non-ionic surfactants for enhancing the solubility of poorly water-soluble drugs. Griseofulvin was selected as a model drug candidate enabling comparisons to be made with the solubilisation capacities of other poly(ethylene oxide)-based copolymers. UV/Vis and (1)H NMR spectroscopies were used to quantify the enhancement of solubility of griseofulvin in 1 wt% aqueous micellar solutions of Brij 78 (C(18)H(37)E(20)), Brij 98 (C(18)H(35)E(20)) and Brij 700 (C(18)H(37)E(100)) (where E represents the OCH(2)CH(2) unit of the poly(ethylene oxide) chain) at 25, 37 and 40 °C. Solubilisation capacities (S(cp) expressed as mg griseofulvin per g Brij) were similar for Brij 78 and 98 (range 6-11 mg g(-1)) but lower for Brij 700 (3-4 mg g(-1)) as would be expected for the surfactant with the higher ethylene oxide content. The drug loading capacity of micelles of Brij 78 was higher than many di- and triblock copolymers with hydrophilic E-blocks specifically designed for enhancement of drug solubility.

  17. Information capacity of specific interactions

    PubMed Central

    Huntley, Miriam H.; Murugan, Arvind; Brenner, Michael P.

    2016-01-01

    Specific interactions are a hallmark feature of self-assembly and signal-processing systems in both synthetic and biological settings. Specificity between components may arise from a wide variety of physical and chemical mechanisms in diverse contexts, from DNA hybridization to shape-sensitive depletion interactions. Despite this diversity, all systems that rely on interaction specificity operate under the constraint that increasing the number of distinct components inevitably increases off-target binding. Here we introduce “capacity,” the maximal information encodable using specific interactions, to compare specificity across diverse experimental systems and to compute how specificity changes with physical parameters. Using this framework, we find that “shape” coding of interactions has higher capacity than chemical (“color”) coding because the strength of off-target binding is strongly sublinear in binding-site size for shapes while being linear for colors. We also find that different specificity mechanisms, such as shape and color, can be combined in a synergistic manner, giving a capacity greater than the sum of the parts. PMID:27155013

  18. Health reform requires policy capacity.

    PubMed

    Forest, Pierre-Gerlier; Denis, Jean-Louis; Brown, Lawrence D; Helms, David

    2015-04-17

    Among the many reasons that may limit the adoption of promising reform ideas, policy capacity is the least recognized. The concept itself is not widely understood. Although policy capacity is concerned with the gathering of information and the formulation of options for public action in the initial phases of policy consultation and development, it also touches on all stages of the policy process, from the strategic identification of a problem to the actual development of the policy, its formal adoption, its implementation, and even further, its evaluation and continuation or modification. Expertise in the form of policy advice is already widely available in and to public administrations, to well-established professional organizations like medical societies and, of course, to large private-sector organizations with commercial or financial interests in the health sector. We need more health actors to join the fray and move from their traditional position of advocacy to a fuller commitment to the development of policy capacity, with all that it entails in terms of leadership and social responsibility. © 2015 by Kerman University of Medical Sciences.

  19. Flying Training Capacity Model: Initial Results

    DTIC Science & Technology

    2005-06-21

    numbers by base • FTRAP model is not versatile • Excel spreadsheets based on corporate knowledge • Requires flying training subject matter expert ( SME ... IFR & VFR operations • Capacity given in terms of runway operations per year • AETC Capacity Metrics - Graduates • Based on sortie generation • Consider...Pilots (IPs) from each course • Airspace capacities from base operations SMEs • Runway capacities • Military Operating Area capacities (including aux

  20. Impaired procedural learning in language impairment: results from probabilistic categorization.

    PubMed

    Kemeny, Ferenc; Lukacs, Agnes

    2010-03-01

    The Weather Prediction (WP) Task is a classical task of probabilistic category learning generally used for examining the dissociation of procedural and declarative memory. The current study focuses on performance of children with language impairment (LI) and compares their performance to that of typically developing (TD) children and adults with the aim of testing the procedural deficit hypothesis of LI (PDH; Ullman & Pierpont, 2005), which states that language impairment is not a specific linguistic phenomenon, but results from the dysfunction of a more general cognitive system: the procedural system. To test the generality of the procedural impairment, we needed a task that is dissimilar from language in that it does not build on sequential information. Children with language impairment show deficient learning on the Weather Prediction Task, which already appears at the early stages of the task. These results, in line with the PDH, point to the deficit of the procedural system in language impairment going beyond the language system. Whether this deficit is selective to the procedural system or is complemented by deficits in the declarative system is the subject of future studies.

  1. Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity.

    PubMed

    Choi, Joungil; Chandrasekaran, Krish; Demarest, Tyler G; Kristian, Tibor; Xu, Su; Vijaykumar, Kadambari; Dsouza, Kevin Geoffrey; Qi, Nathan R; Yarowsky, Paul J; Gallipoli, Rao; Koch, Lauren G; Fiskum, Gary M; Britton, Steven L; Russell, James W

    2014-08-01

    Diabetes leads to cognitive impairment and is associated with age-related neurodegenerative diseases including Alzheimer's disease (AD). Thus, understanding diabetes-induced alterations in brain function is important for developing early interventions for neurodegeneration. Low-capacity runner (LCR) rats are obese and manifest metabolic risk factors resembling human "impaired glucose tolerance" or metabolic syndrome. We examined hippocampal function in aged LCR rats compared to their high-capacity runner (HCR) rat counterparts. Hippocampal function was examined using proton magnetic resonance spectroscopy and imaging, unbiased stereology analysis, and a Y maze. Changes in the mitochondrial respiratory chain function and levels of hyperphosphorylated tau and mitochondrial transcriptional regulators were examined. The levels of glutamate, myo-inositol, taurine, and choline-containing compounds were significantly increased in the aged LCR rats. We observed a significant loss of hippocampal neurons and impaired cognitive function in aged LCR rats. Respiratory chain function and activity were significantly decreased in the aged LCR rats. Hyperphosphorylated tau was accumulated within mitochondria and peroxisome proliferator-activated receptor-gamma coactivator 1α, the NAD(+)-dependent protein deacetylase sirtuin 1, and mitochondrial transcription factor A were downregulated in the aged LCR rat hippocampus. These data provide evidence of a neurodegenerative process in the hippocampus of aged LCR rats, consistent with those seen in aged-related dementing illnesses such as AD in humans. The metabolic and mitochondrial abnormalities observed in LCR rat hippocampus are similar to well-described mechanisms that lead to diabetic neuropathy and may provide an important link between cognitive and metabolic dysfunction.

  2. Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity

    PubMed Central

    Choi, Joungil; Chandrasekaran, Krish; Demarest, Tyler G; Kristian, Tibor; Xu, Su; Vijaykumar, Kadambari; Dsouza, Kevin Geoffrey; Qi, Nathan R; Yarowsky, Paul J; Gallipoli, Rao; Koch, Lauren G; Fiskum, Gary M; Britton, Steven L; Russell, James W

    2014-01-01

    Objectives Diabetes leads to cognitive impairment and is associated with age-related neurodegenerative diseases including Alzheimer's disease (AD). Thus, understanding diabetes-induced alterations in brain function is important for developing early interventions for neurodegeneration. Low-capacity runner (LCR) rats are obese and manifest metabolic risk factors resembling human “impaired glucose tolerance” or metabolic syndrome. We examined hippocampal function in aged LCR rats compared to their high-capacity runner (HCR) rat counterparts. Methods Hippocampal function was examined using proton magnetic resonance spectroscopy and imaging, unbiased stereology analysis, and a Y maze. Changes in the mitochondrial respiratory chain function and levels of hyperphosphorylated tau and mitochondrial transcriptional regulators were examined. Results The levels of glutamate, myo-inositol, taurine, and choline-containing compounds were significantly increased in the aged LCR rats. We observed a significant loss of hippocampal neurons and impaired cognitive function in aged LCR rats. Respiratory chain function and activity were significantly decreased in the aged LCR rats. Hyperphosphorylated tau was accumulated within mitochondria and peroxisome proliferator-activated receptor-gamma coactivator 1α, the NAD+-dependent protein deacetylase sirtuin 1, and mitochondrial transcription factor A were downregulated in the aged LCR rat hippocampus. Interpretation These data provide evidence of a neurodegenerative process in the hippocampus of aged LCR rats, consistent with those seen in aged-related dementing illnesses such as AD in humans. The metabolic and mitochondrial abnormalities observed in LCR rat hippocampus are similar to well-described mechanisms that lead to diabetic neuropathy and may provide an important link between cognitive and metabolic dysfunction. PMID:25356430

  3. Declining physical capacity but maintained aerobic activity in early Alzheimer's disease.

    PubMed

    Cedervall, Ylva; Kilander, Lena; Aberg, Anna Cristina

    2012-05-01

    The longitudinal influences on physical capacity and habitual aerobic activity level in the early stages of Alzheimer's disease (AD) are unclear. Therefore, changes in physical capacity and aerobic activity level were evaluated. Twenty-five individuals with AD were assessed annually for 2 years, by 10-m walk test, 6-minute walk test, and timed up-and-go (TUG) single/dual tasks. Habitual aerobic activity was assessed by diary registrations. The AD group showed a lower physical capacity than controls at baseline but comparable levels of aerobic activity. During the follow-up period, physical capacity declined in the AD group, but the aerobic activity levels changed only marginally. Our results show that in the early stages of AD, people are capable of maintaining health-promoting aerobic activity levels, despite a decline in their physical capacity. Additionally, it appears that cognitive dysfunction contributes to an impaired physical capacity. The TUG tasks might, therefore, be useful for detecting early signs of cognitive impairment.

  4. Exercise capacity is not impaired after acute alcohol ingestion: a pilot study.

    PubMed

    Popovic, Dejana; Damjanovic, Svetozar S; Plecas-Solarovic, Bosiljka; Pešić, Vesna; Stojiljkovic, Stanimir; Banovic, Marko; Ristic, Arsen; Mantegazza, Valentina; Agostoni, Piergiuseppe

    2016-12-01

    The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated.We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5 g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10 min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00 ± 0.00 to 1.25 ± 0.54‰ (P < 0.001). Basal echocardiographic and spirometric parameters were normal and remained so after acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2 = 3008 ± 638 vs. 2900 ± 543 ml/min, ns; peak workload = 269 ± 53 vs. 249 ± 40 W, ns; test duration 13.7 ± 2.2 vs. 13.3 ± 1.7 min, ns; VE/VCO2 22.1 ± 1.4 vs. 23.3 ± 2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28 ± 2.5 vs. 30.4 ± 3.2, P = 0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17 ± 0.02 vs. 1.14 ± 0.04, P = 0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism.

  5. A dynamic test to assess learning capacity in people with severe impairments.

    PubMed

    Hessels-Schlatter, Christine

    2002-09-01

    Because traditional intelligence tests do not allow a reliable and valid estimate of the general cognitive abilities of individuals with IQs lower than 55, a dynamic test of analogical reasoning (Analogical Reasoning Learning Test-ARLT) was constructed for use with this population. The aim of the test is to distinguish individuals who could undergo more ambitious schooling and cognitive training from those who would profit little or none from such an intervention. Internal consistency and test-retest reliability of this measure are high. Discriminant and predictive validity, assessed with another learning test and with a one-month training on inductive reasoning, respectively, are satisfactory. The test is seen as a useful tool for diagnostic differentiation among low performers.

  6. Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet.

    PubMed

    van Haare, Judith; Kooi, M Eline; Vink, Hans; Post, Mark J; van Teeffelen, Jurgen W G E; Slenter, Jos; Munts, Chantal; Cobelens, Hanneke; Strijkers, Gustav J; Koehn, Dennis; van Bilsen, Marc

    2015-11-17

    It remains to be established if, and to what extent, the coronary microcirculation becomes compromised during the development of obesity and insulin resistance. Recent studies suggest that changes in endothelial glycocalyx properties contribute to microvascular dysfunction under (pre-)diabetic conditions. Accordingly, early effects of diet-induced obesity on myocardial perfusion and function were studied in rats under baseline and hyperaemic conditions. Rats were fed a high fat diet (HFD) for 6 weeks and myocardial microvascular perfusion was determined using first-pass perfusion MRI before and after adenosine infusion. The effect of HFD on microcirculatory properties was also assessed by sidestream darkfield (SDF) imaging of the gastrocnemius muscle. HFD-fed rats developed central obesity and insulin sensitivity was reduced as evidenced by the marked reduction in insulin-induced phosphorylation of Akt in both cardiac and gastrocnemius muscle. Early diet-induced obesity did not lead to hypertension or cardiac hypertrophic remodeling. In chow-fed, control rats a robust increase in cardiac microvascular perfusion was observed upon adenosine infusion (+40%; p < 0.05). In contrast, the adenosine response was abrogated in rats on a HFD (+8%; N.S.). HFD neither resulted in rarefaction or loss of glycocalyx integrity in skeletal muscle, nor reduced staining intensity of the glycocalyx of cardiac capillaries. Alterations in coronary microcirculatory function as assessed by first-pass perfusion MRI represent one of the earliest obesity-related cardiac adaptations that can be assessed non-invasively. In this early stage of insulin resistance, disturbances in glycocalyx barrier properties appeared not to contribute to the observed changes in coronary microvascular function.

  7. Sentence Repetition Accuracy in Adults with Developmental Language Impairment: Interactions of Participant Capacities and Sentence Structures

    ERIC Educational Resources Information Center

    Poll, Gerard H.; Miller, Carol A.; van Hell, Janet G.

    2016-01-01

    Purpose: We asked whether sentence repetition accuracy could be explained by interactions of participant processing limitations with the structures of the sentences. We also tested a prediction of the procedural deficit hypothesis (Ullman & Pierpont, 2005) that adjuncts are more difficult than arguments for individuals with developmental…

  8. High Capacity Phase/Amplitude Modulated Optical Communication Systems and Nonlinear Inter-Channel Impairments

    NASA Astrophysics Data System (ADS)

    Tavassoli, Vahid

    This thesis studies and mathematically models nonlinear interactions among channels of modern high bit rate (amplitude/) phase modulated optical systems. First, phase modulated analogue systems are studied and a differential receiving method is suggested with experimental validation. The main focus of the rest of the thesis is on digital advanced modulation format systems. Cross-talk due to fiber Kerr nonlinearity in two-format hybrid systems as well as 16-QAM systems is mathematically modelled and verified by simulation for different system parameters. A comparative study of differential receivers and coherent receivers is also given for hybrid systems. The model is based on mathematically proven assumptions and provides an intuitive analytical understanding of nonlinear cross-talk in such systems.

  9. Discovery and characterization of a cytochrome b5 variant in humans with impaired hydroxylamine reduction capacity.

    PubMed

    Kurian, Joseph R; Longlais, Brett J; Trepanier, Lauren A

    2007-08-01

    We have shown that cytochrome b5 (cyt b5), along with its reductase, NADH cytochrome b5 reductase (b5R), is capable of direct xenobiotic biotransformation. We hypothesized that functionally significant genetic variability in cyt b5 could be found in healthy individuals. Cyt b5 cDNAs were prepared from peripheral blood mononuclear cells from 63 individuals. One individual was heterozygous for a sequence variant in cyt b5 (A178G), with a predicted amino acid substitution of T60A. This variant, when expressed in Escherichia. coli, maintained a similar Vmax for the hydroxylamines of sulfamethoxazole, 4-aminobiphenyl, and 2-amino-l-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), compared with wild type cyt b5, with a modestly increased Km (2 to 3.5-fold) for each substrate. When expressed in a mammalian system (HeLa cells), however, T60A was associated with a 70% reduction in cyt b5 protein expression compared with wild type. mRNA expression for both isoforms were comparable in HeLa cells, and translation of these mRNAs in a rabbit reticulocyte lysate system with inhibited proteasomal machinery were also similar. Incubation of these translated enzymes with uninhibited rabbit reticulocyte lysate, however, indicated greater susceptibility of T60A to proteasomal degradation. These data indicate that a naturally occurring variant in cyt b5, T60A, leads to modestly altered affinity for hydroxylamine substrates and dramatically reduced cyt b5 expression. Work is underway to determine the prevalence of this and other variants in cyt b5 or b5R in a larger population, and to determine the association of such variants with differences in hydroxylamine reduction in vivo.

  10. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity

    USDA-ARS?s Scientific Manuscript database

    Obesity is a risk factor for cardiovascular disease and is strongly associated with insulin resistance and type 2 diabetes. Recent studies in obese humans and animals demonstrated increased myocardial oxygen consumption (MVO2) and reduced cardiac efficiency (CE); however, the underlying mechanisms r...

  11. Sentence Repetition Accuracy in Adults with Developmental Language Impairment: Interactions of Participant Capacities and Sentence Structures

    ERIC Educational Resources Information Center

    Poll, Gerard H.; Miller, Carol A.; van Hell, Janet G.

    2016-01-01

    Purpose: We asked whether sentence repetition accuracy could be explained by interactions of participant processing limitations with the structures of the sentences. We also tested a prediction of the procedural deficit hypothesis (Ullman & Pierpont, 2005) that adjuncts are more difficult than arguments for individuals with developmental…

  12. Single water entropy: hydrophobic crossover and application to drug binding.

    PubMed

    Sasikala, Wilbee D; Mukherjee, Arnab

    2014-09-11

    Entropy of water plays an important role in both chemical and biological processes e.g. hydrophobic effect, molecular recognition etc. Here we use a new approach to calculate translational and rotational entropy of the individual water molecules around different hydrophobic and charged solutes. We show that for small hydrophobic solutes, the translational and rotational entropies of each water molecule increase as a function of its distance from the solute reaching finally to a constant bulk value. As the size of the solute increases (0.746 nm), the behavior of the translational entropy is opposite; water molecules closest to the solute have higher entropy that reduces with distance from the solute. This indicates that there is a crossover in translational entropy of water molecules around hydrophobic solutes from negative to positive values as the size of the solute is increased. Rotational entropy of water molecules around hydrophobic solutes for all sizes increases with distance from the solute, indicating the absence of crossover in rotational entropy. This makes the crossover in total entropy (translation + rotation) of water molecule happen at much larger size (>1.5 nm) for hydrophobic solutes. Translational entropy of single water molecule scales logarithmically (Str(QH) = C + kB ln V), with the volume V obtained from the ellipsoid of inertia. We further discuss the origin of higher entropy of water around water and show the possibility of recovering the entropy loss of some hypothetical solutes. The results obtained are helpful to understand water entropy behavior around various hydrophobic and charged environments within biomolecules. Finally, we show how our approach can be used to calculate the entropy of the individual water molecules in a protein cavity that may be replaced during ligand binding.

  13. Molecular Mechanisms of Pharmaceutical Drug Binding into Calsequestrin

    PubMed Central

    Subra, Arun K.; Nissen, Mark S.; Lewis, Kevin M.; Muralidharan, Ashwin K.; Sanchez, Emiliano J.; Milting, Hendrik; Kang, ChulHee

    2012-01-01

    Calsequestrin (CASQ) is a major Ca2+-storage/buffer protein present in the sarcoplasmic reticulum of both skeletal (CASQ1) and cardiac (CASQ2) muscles. CASQ has significant affinity for a number of pharmaceutical drugs with known muscular toxicities. Our approach, with in silico molecular docking, single crystal X-ray diffraction, and isothermal titration calorimetry (ITC), identified three distinct binding pockets on the surface of CASQ2, which overlap with 2-methyl-2,4-pentanediol (MPD) binding sites observed in the crystal structure. Those three receptor sites based on canine CASQ1 crystal structure gave a high correlation (R2 = 0.80) to our ITC data. Daunomycin, doxorubicin, thioridazine, and trifluoperazine showed strong affinity to the S1 site, which is a central cavity formed between three domains of CASQ2. Some of the moderate-affinity drugs and some high-affinity drugs like amlodipine and verapamil displayed their binding into S2 sites, which are the thioredoxin-like fold present in each CASQ domain. Docking predictions combined with dissociation constants imply that presence of large aromatic cores and less flexible functional groups determines the strength of binding affinity to CASQ. In addition, the predicted binding pockets for both caffeine and epigallocatechin overlapped with the S1 and S2 sites, suggesting competitive inhibition by these natural compounds as a plausible explanation for their antagonistic effects on cardiotoxic side effects. PMID:23203067

  14. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

    PubMed

    Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-05-02

    DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases.

  15. Interactive association of drugs binding to human serum albumin.

    PubMed

    Yang, Feng; Zhang, Yao; Liang, Hong

    2014-02-27

    Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and efficacy and ultimately altering the drug's pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used in clinical settings as a drug delivery system due to its potential for improving targeting while decreasing the side effects of drugs. It is thus of great importance from the viewpoint of pharmaceutical sciences to clarify the structure, function, and properties of HSA-drug complexes. This review will succinctly outline the properties of binding site of drugs in IIA subdomain within the structure of HSA. We will also give an overview on the binding characterization of interactive association of drugs to human serum albumin that may potentially lead to significant clinical applications.

  16. The enigmatic drug binding site for sodium channel inhibitors.

    PubMed

    Mike, Arpad; Lukacs, Peter

    2010-11-01

    Local anesthetics have been in clinical use since 1884, and different aspects of the local anesthetic binding site have been studied in enormous detail. In spite of all these efforts, some of the most fundamental questions--such as which exact residues constitute the binding site, how many binding sites exist, do local anesthetics share their binding site(s) with other sodium channel inhibitors, and what are the mechanisms of inhibition--are still largely unanswered. We review accumulated data on the "local anesthetic receptor"and discuss controversial points, such as possible mechanisms of inhibition, the possibility of additional binding sites, the orientation of S6 helices, and the internal vs. external position of the anticonvulsant binding site. We describe the four following specific groups of functionally important residues: i) conserved asparagines six residues below the hinge residues; we propose that they are oriented toward the external surface of S6 helices, and have a critical role in the coupling of voltage sensors to gating, ii) residues lining the inner vestibule and constructing the "orthodox" binding site, iii) residues around the outer vestibule, which have been proposed to constitute an alternative external binding site, and iv) residues determining external access for quaternary amine inhibitors, such as QX314. We conclude that sodium channel inhibitors must be heterogenous in terms of binding sites and inhibition mechanisms, and propose that this heterogeneity should be taken into consideration during drug development.

  17. Impaired Pain Processing Correlates with Cognitive Impairment in Parkinson's Disease

    PubMed Central

    Okada, Akinori; Nakamura, Tomohiko; Suzuki, Junichiro; Suzuki, Masashi; Hirayama, Masaaki; Katsuno, Masahisa; Sobue, Gen

    2016-01-01

    Objective Pain and cognitive impairment are important clinical features in patients with Parkinson's disease (PD). Although pain processing is associated with the limbic system, which is also closely linked to the cognitive function, the association between pain and cognitive impairment in PD is still not well understood. The aim of the study was to investigate the association between pain processing and cognitive impairment in patients with PD. Methods Forty-three patients with PD and 22 healthy subjects were studied. Pain-related somatosensory evoked potentials (SEPs) were generated using a thin needle electrode to stimulate epidermal Aδ fibers. Cognitive impairment was evaluated using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery, and Japanese version of the Montreal Cognitive Assessment (MoCA-J), and their correlation with pain-related SEPs was investigated. Results The N1/P1 amplitude was significantly lower in PD patients than the controls. N1/P1 peak-to-peak amplitudes correlated with the MMSE (r=0.66, p<0.001) and MoCA-J scores (r=0.38, p<0.01) in patients with PD. These amplitudes also strongly correlated with the domains of attention and memory in the MMSE (attention, r=0.52, p<0.001; memory, r=0.40, p<0.01) and MoCA-J (attention, r=0.45, p<0.005; memory, r=0.48, p<0.001), but not in control subjects. Conclusion A good correlation was observed between the decreased amplitudes of pain-related SEPs and an impairment of attention and memory in patients with PD. Our results suggest that pathological abnormalities of the pain pathway are significantly linked to cognitive impairment in PD. PMID:27803403

  18. Auditory Short-Term Memory Capacity Correlates with Gray Matter Density in the Left Posterior STS in Cognitively Normal and Dyslexic Adults

    ERIC Educational Resources Information Center

    Richardson, Fiona M.; Ramsden, Sue; Ellis, Caroline; Burnett, Stephanie; Megnin, Odette; Catmur, Caroline; Schofield, Tom M.; Leff, Alex P.; Price, Cathy J.

    2011-01-01

    A central feature of auditory STM is its item-limited processing capacity. We investigated whether auditory STM capacity correlated with regional gray and white matter in the structural MRI images from 74 healthy adults, 40 of whom had a prior diagnosis of developmental dyslexia whereas 34 had no history of any cognitive impairment. Using…

  19. Auditory Short-Term Memory Capacity Correlates with Gray Matter Density in the Left Posterior STS in Cognitively Normal and Dyslexic Adults

    ERIC Educational Resources Information Center

    Richardson, Fiona M.; Ramsden, Sue; Ellis, Caroline; Burnett, Stephanie; Megnin, Odette; Catmur, Caroline; Schofield, Tom M.; Leff, Alex P.; Price, Cathy J.

    2011-01-01

    A central feature of auditory STM is its item-limited processing capacity. We investigated whether auditory STM capacity correlated with regional gray and white matter in the structural MRI images from 74 healthy adults, 40 of whom had a prior diagnosis of developmental dyslexia whereas 34 had no history of any cognitive impairment. Using…

  20. 20 CFR 416.923 - Multiple impairments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Multiple impairments. 416.923 Section 416.923... DISABLED Determining Disability and Blindness Evaluation of Disability § 416.923 Multiple impairments. In... the combined effect of all of your impairments without regard to whether any such impairment,...

  1. Gadobutrol in Renally Impaired Patients

    PubMed Central

    Michaely, Henrik J.; Aschauer, Manuela; Deutschmann, Hannes; Bongartz, Georg; Gutberlet, Matthias; Woitek, Ramona; Ertl-Wagner, Birgit; Kucharczyk, Walter; Hammerstingl, Renate; De Cobelli, Francesco; Rosenberg, Martin; Balzer, Thomas; Endrikat, Jan

    2017-01-01

    Objective The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF). Materials and Methods We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF. Conclusions No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases. PMID:27529464

  2. Theatre fleet's vital additional capacity.

    PubMed

    2012-11-01

    Vanguard Healthcare's fleet of mobile surgical facilities has been deployed to healthcare sites throughout Europe and beyond for over a decade, providing vital additional clinical capacity when existing buildings are refurbished or upgraded, in the event of flood or fire, or simply to help hospitals cater for rising demand. It is a combination of careful planning, teamwork, and the specialist expertise of Vanguard's personnel--many with a clinical background--that ensures not only each unit's successful installation, but equally its subsequent running, servicing, and maintenance, the company explains.

  3. Developing Ministerial Collaborative Planning Capacity

    DTIC Science & Technology

    2012-03-14

    the MNSTC-I era and, its successor organization the Iraq Training and Advisory Mission for the Ministry of Interior ( ITAM -MoI) that focused on the...organization can exercise influence over.26 The training partnership between the DRMI and the MoI was one of the few success stories in ITAM -MoI’s...efforts to develop institutional capacity within the MoI. Over a nineteen-month period, the DRMI, MoI JRC, and ITAM -MoI partnered to host 14

  4. Physical impairment aware transparent optical networks

    NASA Astrophysics Data System (ADS)

    Antona, Jean-Christophe; Morea, Annalisa; Zami, Thierry; Leplingard, Florence

    2009-11-01

    As illustrated by optical fiber and optical amplification, optical telecommunications have appeared for the last ten years as one of the most promising candidates to increase the transmission capacities. More recently, the concept of optical transparency has been investigated and introduced: it consists of the optical routing of Wavelength Division Multiplexed (WDM) channels without systematic optoelectronic processing at nodes, as long as propagation impairments remain acceptable [1]. This allows achieving less power-consuming, more scalable and flexible networks, and today partial optical transparency has become a reality in deployed systems. However, because of the evolution of traffic features, optical networks are facing new challenges such as demand for higher transmitted capacity, further upgradeability, and more automation. Making all these evolutions compliant on the same current network infrastructure with a minimum of upgrades is one of the main issues for equipment vendors and operators. Hence, an automatic and efficient management of the network needs a control plan aware of the expected Quality of Transmission (QoT) of the connections to set-up with respect to numerous parameters such as: the services demanded by the customers in terms of protection/restoration; the modulation rate and format of the connection under test and also of its adjacent WDM channels; the engineering rules of the network elements traversed with an accurate knowledge of the associated physical impairments. Whatever the method and/or the technology used to collect this information, the issue about its accuracy is one of the main concerns of the network system vendors, because an inaccurate knowledge could yield a sub-optimal dimensioning and so additional costs when installing the network in the field. Previous studies [1], [2] illustrated the impact of this knowledge accuracy on the ability to predict the connection feasibility. After describing usual methods to build

  5. Phonological working memory impairments in children with specific language impairment: where does the problem lie?

    PubMed

    Alt, Mary

    2011-01-01

    The purpose of this study was to determine which factors contribute to the lexical learning deficits of children with specific language impairment (SLI). Participants included 40 7-8-year old participants, half of whom were diagnosed with SLI and half of whom had normal language skills. We tested hypotheses about the contributions to word learning of the initial encoding of phonological information and the link to long-term memory. Children took part in a computer-based fast-mapping task which manipulated word length and phonotactic probability to address the hypotheses. The task had a recognition and a production component. Data were analyzed using mixed ANOVAs with post-hoc testing. Results indicate that the main problem for children with SLI is with initial encoding, with implications for limited capacity. There was not strong evidence for specific deficits in the link to long-term memory. We were able to ascertain which aspects of lexical learning are most problematic for children with SLI in terms of fast-mapping. These findings may allow clinicians to focus intervention on known areas of weakness. Future directions include extending these findings to slow mapping scenarios. The reader will understand how different components of phonological working memory contribute to the word learning problems of children with specific language impairment. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Functional impairment of hematopoietic progenitor cells in patients with coronary heart disease.

    PubMed

    Liguori, Antonio; Fiorito, Carmela; Balestrieri, Maria Luisa; Crimi, Ettore; Bruzzese, Giuseppe; Williams-Ignarro, Sharon; D'Amora, Maurizio; Sommese, Linda; Grimaldi, Vincenzo; Minucci, Pellegrino Biagio; Giovane, Alfonso; Farzati, Bartolomeo; Ignarro, Louis J; Napoli, Claudio

    2008-03-01

    The circulating form of endothelial progenitors cells (EPCs) are derived from bone marrow (BM)-derived hematopoietic stem cells (HSCs). Enhanced mobilization of EPCs was shown to be linked to cardiac diseases. This study investigated whether reduced EPC levels in advanced coronary heart disease (CHD) are secondary to a functional exhaustion of HSCs in the BM or to reduced mobilization. Number and functional properties of EPCs were assessed in 15 healthy controls, and 40 patients with CHD. The colony-forming unit (CFU) capacity of BM-derived mononuclear cells and the CD34+ HSC number were examined in four healthy volunteers, and 15 CHD patients. EPC number was reduced in CHD patients (P < 0.01 vs. controls). Moreover, the migratory capacity was significantly impaired in EPCs of CHD patients (P < 0.05 vs. controls). On multivariate analysis, CHD was an independent predictor of functional EPC impairment. CFUs were reduced in CHD patients (59.6 +/- 21.2 vs. 75.4 +/- 25.8 in controls, P < 0.05). CHD was also predictor of impaired CFU capacity. In this small clinical study, CHD is associated with selective impairment of HSC function in the BM and in the peripheral blood, which may contribute to impairment of cardiac function.

  7. Mental juggling: when does multitasking impair reading comprehension?

    PubMed

    Cho, Kit W; Altarriba, Jeanette; Popiel, Maximilian

    2015-01-01

    The present study investigated the conditions under which multitasking impairs reading comprehension. Participants read prose passages (the primary task), some of which required them to perform a secondary task. In Experiment 1, we compared two different types of secondary tasks (answering trivia questions and solving math problems). Reading comprehension was assessed using a multiple-choice test that measured both factual and conceptual knowledge. The results showed no observable detrimental effects associated with multitasking. In Experiment 2, the secondary task was a cognitive load task that required participants to remember a string of numbers while reading the passages. Performance on the reading comprehension test was lower in the cognitive load conditions relative to the no-load condition. The present study delineates the conditions under which multitasking can impair or have no effect on reading comprehension. These results further our understanding of our capacity to multitask and have practical implications in our technologically advanced society in which multitasking has become commonplace.

  8. Human Impairment from Living near Confined Animal (Hog) Feeding Operations

    PubMed Central

    Kilburn, Kaye H.

    2012-01-01

    Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neurophysiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neurobehavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neurobehavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas. PMID:22496706

  9. A Case Study of Parental Perceptions of Literacy Skill Development for Severe Speech Impairments

    ERIC Educational Resources Information Center

    Sweat, Karen

    2014-01-01

    Students exhibiting speech deficits may not have the appropriate skills or support structures necessary to obtain adequate or acceptable literacy development as mixed results from past research have indicated that some students with speech impairments have the capacity to gain appropriate literacy skills. The purpose of the qualitative holistic…

  10. The Impact of Dual Tasking on Sentence Comprehension in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Leclercq, Anne-Lise; Majerus, Steve; Prigent, Gaid; Maillart, Christelle

    2013-01-01

    Purpose: In this study, the authors assessed the hypothesis of a limitation in attentional allocation capacity as underlying poor sentence comprehension in children with specific language impairment (SLI). Method: Fifteen children with SLI, 15 age-matched controls, and 15 grammar-matched controls participated in the study. Sixty sentences were…

  11. The Impact of Dual Tasking on Sentence Comprehension in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Leclercq, Anne-Lise; Majerus, Steve; Prigent, Gaid; Maillart, Christelle

    2013-01-01

    Purpose: In this study, the authors assessed the hypothesis of a limitation in attentional allocation capacity as underlying poor sentence comprehension in children with specific language impairment (SLI). Method: Fifteen children with SLI, 15 age-matched controls, and 15 grammar-matched controls participated in the study. Sixty sentences were…

  12. Psycholinguistic Profiling Differentiates Specific Language Impairment from Typical Development and from Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Redmond, Sean M.; Thompson, Heather L.; Goldstein, Sam

    2011-01-01

    Purpose: Practitioners must have confidence in the capacity of their language measures to discriminate developmental language disorders from typical development and from other common disorders. In this study, psycholinguistic profiles were collected from 3 groups: children with specific language impairment (SLI), children with…

  13. Complex Sentence Comprehension and Working Memory in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Montgomery, James W.; Evans, Julia L.

    2009-01-01

    Purpose: This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method: Twenty-four children with SLI, 18 age-matched…

  14. A Functional Magnetic Resonance Imaging Investigation of Verbal Working Memory in Adolescents with Specific Language Impairment

    ERIC Educational Resources Information Center

    Weismer, Susan Ellis; Plante, Elena; Jones, Maura; Tomblin, Bruce J.

    2005-01-01

    This study used neuroimaging and behavioral techniques to examine the claim that processing capacity limitations underlie specific language impairment (SLI). Functional magnetic resonance imaging (fMRI) was used to investigate verbal working memory in adolescents with SLI and normal language (NL) controls. The experimental task involved a modified…

  15. Complex Sentence Comprehension and Working Memory in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Montgomery, James W.; Evans, Julia L.

    2009-01-01

    Purpose: This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method: Twenty-four children with SLI, 18 age-matched…

  16. Psycholinguistic Profiling Differentiates Specific Language Impairment from Typical Development and from Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Redmond, Sean M.; Thompson, Heather L.; Goldstein, Sam

    2011-01-01

    Purpose: Practitioners must have confidence in the capacity of their language measures to discriminate developmental language disorders from typical development and from other common disorders. In this study, psycholinguistic profiles were collected from 3 groups: children with specific language impairment (SLI), children with…

  17. Cognitive impairment in major depression.

    PubMed

    Marazziti, Donatella; Consoli, Giorgio; Picchetti, Michela; Carlini, Marina; Faravelli, Luca

    2010-01-10

    In the past decade, a growing bulk of evidence has accumulated to suggest that patients suffering from major depression (MD) present some cognitive disturbances, such as impairment in attention, working memory, and executive function, including cognitive inhibition, problem- and task-planning. If the results of short-term memory assessment in depressed patients are equivocal, a general consensus exists that memory problems are secondary to attentional dysfunctions, and reflect the inability to concentrate. Moreover, both unipolar and bipolar patients show evidence of impaired verbal learning that has been commonly interpreted as reflecting an inability to transfer information from short-term to long-term storage. According to some authors, there would be a gender-related as well age-related specificity of some disturbances. Depressed patients also show impairments of executive functions and their recent exploration through brain imaging techniques has recently permitted to formulate some general hypotheses on the possible involvement of different brain areas in MD.

  18. Associations between Manual Abilities, Gross Motor Function, Epilepsy, and Mental Capacity in Children with Cerebral Palsy

    PubMed Central

    GAJEWSKA, Ewa; SOBIESKA, Magdalena; SAMBORSKI, Włodzimierz

    2014-01-01

    Objective This study aimed to evaluate gross motor function and hand function in children with cerebral palsy to explore their association with epilepsy and mental capacity. Material & Methods The research investigating the association between gross and fine motor function and the presence of epilepsy and/or mental impairment was conducted on a group of 83 children (45 girls, 38 boys). Among them, 41 were diagnosed with quadriplegia, 14 hemiplegia, 18 diplegia, 7 mixed form, and 3 athetosis. A neurologist assessed each child in terms of possible epilepsy and confirmed diagnosis in 35 children. A psychologist assessed the mental level (according to Wechsler) and found 13 children within intellectual norm, 3 children with mild mental impairment, 18 with moderate, 27 with severe, and 22 with profound. Children were then classified based on Gross Motor Function Classification System and Manual Ability Classification Scale. Results The gross motor function and manual performance were analysed in relation to mental impairment and the presence of epilepsy. Epilepsy was found to disturb conscious motor functions, but also higher degree of mental impairment was observed in children with epilepsy. Conclusion The occurrence of epilepsy in children with cerebral palsy is associated with worse manual function. The occurrence of epilepsy is associated with limitations in conscious motor functions. There is an association between epilepsy in children with cerebral palsy and the degree of mental impairment. The occurrence of epilepsy, mainly in children with hemiplegia and diplegia is associated with worse mental capacities. PMID:24949051

  19. Rethinking health research capacity strengthening

    PubMed Central

    Vasquez, Emily; Hirsch, Jennifer S.; Giang, Le Minh; Parker, Richard G.

    2013-01-01

    Health research capacity strengthening (HRCS) is a strategy implemented worldwide to improve the ability of developing countries to tackle the persistent and disproportionate burdens of disease they face. Drawing on a review of existing HRCS literature and our experiences over the course of an NIH-funded HRCS project in Vietnam, we summarise major challenges to the HRCS enterprise at the interpersonal, institutional and macro levels. While over the course of several decades of HRCS initiatives many of these challenges have been well documented, we highlight several considerations that remain under-articulated. We advance critical considerations of the HRCS enterprise by discussing 1) how the organisation of US public health funding shapes the ecology of knowledge production in low- and middle-income country contexts, 2) the barriers US researchers face to effectively collaborating in capacity strengthening for research-to-policy translation, and 3) the potential for unintentional negative consequences if HRCS efforts are not sufficiently reflexive about the limitations of dominant paradigms in public health research and intervention. PMID:23651463

  20. Un Open GIS Capacity Building

    NASA Astrophysics Data System (ADS)

    Albertella, A.; Brovelli, M. A.; Gonzalez Ferreiro, D.

    2017-07-01

    The UN Open GIS Initiative is to identify and develop, under UN guidance, an Open Source GIS bundle that meets the requirements of UN operations, taking full advantage of the expertise of mission partners (partner nations, technology contributing countries, international organizations, academia, NGO's, private sector). The project, started in 2016, is composed by 4 working groups. One of the working group is specifically related to Capacity Building, given its importance for the success of the project. UN Open GIS will be based on some existing open source geospatial software (packages and libraries) with many extensions specifically developed. The users of the platform will be the UN staff supporting with mapping and GIS the peacekeeping missions. Therefore, they are generally expert of this specific domain, even if they are currently using proprietary software. UN Open GIS Capacity Building is specifically thought for covering this gap, providing them the suitable background about open source geospatial software in general and the education tailored to the solution that has been being developed within the project itself.

  1. Control Capacity in Complex Networks

    NASA Astrophysics Data System (ADS)

    Jia, Tao; Liu, Yang-Yu; Slotine, Jean-Jacques; Barabasi, Albert-Laszlo

    2012-02-01

    By combining tools from control theory and network science, an efficient methodology was proposed to identify the minimum sets of driver nodes, whose time-dependent control can guide the whole network to any desired final state. Yet, this minimum driver set (MDS) is usually not unique, but one can often achieve multiple potential control configurations with the same number of driver nodes. Given that some nodes may appear in some MDSs but not in other, a crucial question remain unanswered: what is the role of individual node in controlling a complex system? We first classify a node as critical, redundant, or ordinary if it appears in all, no, or some MDSs. Then we introduce the concept of control capacity as a measure of the frequency that a node is in the MDSs, which quantifies the importance of a given node in maintaining Controllability. To avoid impractical enumeration of all MDSs, we propose an algorithm that uniformly samples the MDS. We use it to explore the control capacity of nodes in complex networks and study how it is related to other characteristics of the network topology.

  2. Mobility in Old Age: Capacity Is Not Performance

    PubMed Central

    Mellone, Sabato; Zijlstra, Wiebren

    2016-01-01

    Background. Outcomes of laboratory-based tests for mobility are often used to infer about older adults' performance in real life; however, it is unclear whether such association exists. We hypothesized that mobility capacity, as measured in the laboratory, and mobility performance, as measured in real life, would be poorly linked. Methods. The sample consisted of 84 older adults (72.5 ± 5.9 years). Capacity was assessed via the iTUG and standard gait parameters (stride length, stride velocity, and cadence). Performance was assessed in real life over a period of 6.95 ± 1.99 days using smartphone technology to calculate following parameters: active and gait time, number of steps, life-space, mean action-range, and maximum action-range. Correlation analyses and stepwise multiple regression analyses were applied. Results. All laboratory measures demonstrated significant associations with the real-life measures (between r = .229 and r = .461). The multiple regression analyses indicated that the laboratory measures accounted for a significant but very low proportion of variance (between 5% and 21%) in real-life measures. Conclusion. In older adults without mobility impairments, capacity-related measures of mobility bear little significance for predicting real-life performance. Hence, other factors play a role in how older people manage their daily-life mobility. This should be considered for diagnosis and treatment of mobility deficits in older people. PMID:27034932

  3. [Impaired wound healing following tonsillectomy].

    PubMed

    Zengel, P; Betz, C S; Berghaus, A; Leunig, A

    2008-07-01

    Tonsillectomy is one of the most commonly performed surgical procedures in the field of otorhinolaryngology. The first tonsillectomy was done about 600 B.C. [3]. This operation is indicated for patients with recurrent tonsillitis, peritonsillar abscess, hypertrophy or asymmetry of the tonsils. Even though a routine procedure, it has a relatively high risk of complications such as post operative hemorrhage, infection or impaired wound healing. The reported case involves a 20 year old female patient who developed velopharyngeal insufficiency as a result of impaired wound healing after tonsillectomy. The patient was treated conservatively and is free of discomfort after 2 months.

  4. Visitation arrangements for impaired parents.

    PubMed

    Montgomery, Stephen A; Street, David F

    2011-07-01

    Forensic mental health professionals are frequently asked to evaluate the parenting skills of divorcing parents because the court seeks help in determining the custody, visitation, and parenting time arrangements for the children. When one of the parents is impaired, the court wants to know the way to help the children have a good relationship with that parent and keep the children safe. There is little empirical research to answer such questions. In this article, the authors describe their methodology for providing useful clinical information to the court to help guide their decisions regarding visitation with impaired parents.

  5. Self-concept, self-esteem, personality traits and psychopathological symptoms in adolescents with and without visual impairment.

    PubMed

    Garaigordobil, Maite; Bernarás, Elena

    2009-05-01

    The purpose of this study was to analyze self-concept, self-esteem, and other personality traits and psychopathological symptoms in subjects with and without visual impairment. The sample was made up of 90 participants aged 12 to 17: 61 with no impairment and 29 with visual impairment. The ANOVA showed that there were no significant differences in self-concept and self-esteem in the samples, but the visually impaired adolescents scored significantly higher in various psychopathological symptoms as well as in their capacity for kind behavior. The ANOVA revealed no gender differences in any variables in adolescents without visual impairment. However, women with visual impairment scored lower in self-esteem and higher in various psychopathological symptoms. Pearson coefficients revealed negative relations between self-concept/self-esteem and all the psychopathological symptoms, and neuroticism, as well as a positive relation with extraversion. Low psychoticism, high extraversion, and low hostility were identified as predictors of high self-concept.

  6. Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia in a rat strain artificially selected and bred for low aerobic running capacity

    PubMed Central

    Høydal, MA; Stølen, TO; Johnsen, AB; Alvez, M; Catalucci, D; Condorelli, G; Koch, LG; Britton, SL; Smith, GL; Wisløff, U

    2014-01-01

    Aim Rats selectively bred for inborn Low Capacity of Running (LCR) display a series of poor health indices where as rats selected for High Capacity of Running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca2+ leak that trigger arrhythmia. Methods We used rats selected for HCR (N=10) or LCR (N=10) to determine the effect of inborn aerobic capacity on Ca2+ leak and susceptibility of ventricular arrhythmia. We studied isolated FURA2/AM loaded cardiomyocytes to detect Ca2+-handling and function on an inverted epi-fluorescence microscope. To determine arrhythmogenicity we did a final experiment with electrical burst pacing in Langendorff perfused hearts. Results Ca2+-handling was impaired by reduced Ca2+ amplitude, prolonged time to 50% Ca2+ decay, and reduced sarcoplasmic reticulum (SR) Ca2+-content. Impaired Ca2+ removal was influenced by reduced SR Ca2+ ATP-ase 2a (SERCA2a) function and increased sodium/Ca2+-exchanger (NCX) in LCR rats. Diastolic Ca2 leak was 87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression levels of phosphorylated theorine-286 CaMKII levels and increased RyR2 phosphorylation at the Serine-2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. Conclusion Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of CaMKII at serine-2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca2+ handling and diastolic Ca2+ leak that results in increased susceptibility to ventricular fibrillation. PMID:24444142

  7. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins... be severe enough to keep you from doing substantial gainful activity, or severe enough so that you...

  8. Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment.

    PubMed

    Marbury, Thomas; Lawitz, Eric; Stonerock, Robert; Gonzalez, Martha; Jiao, James; Breeding, Jim; Haqq, Christopher; Verboven, Peter; Stieltjes, Hans; Yu, Margaret; Molina, Arturo; Acharya, Milin; Chien, Caly; Tran, NamPhuong

    2014-07-01

    Three open-label, single-dose studies investigated the impact of hepatic or renal impairment on abiraterone acetate pharmacokinetics and safety/tolerability in non-cancer patients. Patients (n = 8 each group) with mild/moderate hepatic impairment or end-stage renal disease (ESRD), and age-, BMI-matched healthy controls received a single oral 1,000 mg abiraterone acetate (tablet dose); while patients (n = 8 each) with severe hepatic impairment and matched healthy controls received 125- and 2,000-mg abiraterone acetate (suspension doses), respectively (systemic exposure of abiraterone acetate suspension is approximately half to that of tablet formulation). Blood was sampled at specified timepoints up to 72 or 96 hours postdose to measure plasma abiraterone concentrations. Abiraterone exposure was comparable between healthy controls and patients with mild hepatic impairment or ESRD, but increased by 4-fold in patients with moderate hepatic impairment. Despite a 16-fold reduction in dose, abiraterone exposure in patients with severe hepatic impairment was about 22% and 44% of the Cmax and AUC∞ of healthy controls, respectively. These results suggest that abiraterone pharmacokinetics were not changed markedly in patients with ESRD or mild hepatic impairment. However, the capacity to eliminate abiraterone was substantially compromised in patients with moderate or severe hepatic impairment. A single-dose administration of abiraterone acetate was well-tolerated.

  9. Earnings Capacity, Economic Status, and Poverty

    ERIC Educational Resources Information Center

    Garfinkel, Irwin; Haveman, Robert

    1977-01-01

    "Earnings capacity" is suggested as an alternative to "annual money income" as an indicator of economic status. The socioeconomic and demographic determinants of poverty as measured by earnings capacity and by annual money income are compared and contrasted. (WL)

  10. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  11. U.S. Refining Capacity Utilization

    EIA Publications

    1995-01-01

    This article briefly reviews recent trends in domestic refining capacity utilization and examines in detail the differences in reported crude oil distillation capacities and utilization rates among different classes of refineries.

  12. Earnings Capacity, Economic Status, and Poverty

    ERIC Educational Resources Information Center

    Garfinkel, Irwin; Haveman, Robert

    1977-01-01

    "Earnings capacity" is suggested as an alternative to "annual money income" as an indicator of economic status. The socioeconomic and demographic determinants of poverty as measured by earnings capacity and by annual money income are compared and contrasted. (WL)

  13. Testamentary capacity of the schizophrenic patient.

    PubMed

    Bergman-Levy, Tal; Heinik, Jeremia; Melamed, Yuval

    2014-03-01

    Testamentary capacity refers to an individual's capability to write his or her own will. Psychiatrists are required occasionally to give expert opinions regarding the testamentary capacity of individuals with a medical history or suspected diagnosis of a mental illness. This may stem from the patient/lawyer/ family initiative to explore the current capacity to testate in anticipation of a possible challenge, or may be sought when testamentary capacity of a deceased has been challenged. In this article we examine the medico-legal construct of testamentary capacity of the schizophrenic patient, and discuss the various clinical situations specific to schizophrenic patients, highlighting their impact on the medical opinion regarding testamentary capacity through examining the rulings of Israel's Supreme Court in a specific case where the testamentary capacity of a mentally ill individual who was challenged postmortem, and provide a workable framework for the physician to evaluate the capacity of a schizophrenic patient to write a will..

  14. [Functional impairment associated with cognitive impairment in hospitalised elderly].

    PubMed

    Ocampo-Chaparro, José Mauricio; Mosquera-Jiménez, José Ignacio; Davis, Annabelle S; Reyes-Ortiz, Carlos A

    2017-06-24

    The aim of this study was to analyse the effect of cognitive impairment on functional decline in hospitalised patients aged ≥60 years. Measurements at admission included demographic data, Charlson's comorbidity index, and cognitive impairment (according to education level). Data were also collected on hospital length of stay, depression, and delirium developed during hospitalisation. The outcome, Barthel Index (BI), was measured at admission, discharge, and 1-month post-discharge. Patients with BI≤75 at admission (n=54) or with a missing BI value were excluded (n=1). Multivariate logistic regression analyses were conducted to explore predictive factors with functional decline (BI≤75) from admission to discharge, and 1-month later. Of the 133 patients included, 24.8% and 19.6% had a BI≤75 at discharge and at 1-month, respectively. Compared with men, women had more than double risk for functional decline at discharge and 1-month (P<.05). Compared with those without delirium and without cognitive impairment, those with delirium and cognitive impairment had an increased risk for functional decline (BI≤75) at discharge (OR 5.15, 95% CI; 1.94-13.67), and at 1-month (OR 6.26, 95% CI; 2.30-17.03). Similarly, those with comorbidity (≥2) had increased functional decline at discharge (OR 2.36, 95% CI; 1.14-4.87), and at 1-month after discharge (OR 2.71, 95% CI; 1.25-5.89). Delirium during hospitalisation, together with cognitive impairment on admission, was a strong predictor of functional decline. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Visibility of LED Blocks Mounted on Crosswalk Boundaries for low Visual Capacity.

    PubMed

    Ikeda, Norihiro; Takahashi, Kazuya; Inagaki, Tomoyuki; Sato, Katsuya; Ito, Sin-Ichi; Seiyama, Motohiro; Takeuchi, Kiyohito; Ogino, Hiroshi; Fujisawa, Shoichiro

    2015-01-01

    According to the WHO, about 80% of visually impaired persons in the world are with low visual capacity. It is considered that LVs' safe independent mobility will be improved as employing Tactile Walking Surface Indicators (TWSIs). In the night, guidelines for constructing warning blocks, a kind of tactile surface indicator, have not been well established. Therefore, crossing crosswalks is one of the most dangerous situations for visually impaired persons. We thus developed novel LED blocks that indicate crosswalk boundaries between sidewalks and roadways. This study addresses the LED blocks under various environmental illuminations and illumination from the opposite side of the crossing.

  16. Grammatical sensitivity and working memory in children with language impairment

    PubMed Central

    Marton, Klara; Campanelli, Luca; Farkas, Lajos

    2013-01-01

    Children with primary language impairment (LI) show a deficit in processing different grammatical structures, verb inflections, and syntactically complex sentences among other things (Clahsen–Hansen 1997; Leonard et al. 1997). Cross-linguistic research has shown that the pattern of performance is language-specific. We examined grammatical sensitivity to word order and agreement violations in 50 Hungarian-speaking children with and without LI. The findings suggest a strong association between sensitivity to grammatical violations and working memory capacity. Variations in working memory performance predicted grammatical sensitivity. Hungarian participants with LI exhibited a weakness in detecting both agreement and word order violations. PMID:23440891

  17. Decision-making capacity and competency in the elderly: a clinical and neuropsychological perspective.

    PubMed

    Moberg, Paul J; Rick, Jacqueline H

    2008-01-01

    With our ageing population, the number of older adults with cognitive impairment has also increased. There is both an acute and growing need for evidence-based assessments to identify their decision making capacity and competence. In the present article we (1) present definitions of decision-making capacity and competence, (2) review cognitive functions that are central to decision-making capacity as well as the methods and procedures commonly used to assess these domains, and (3) address the communication of assessment findings to patients and their loved ones. The importance of assessing decision-making capacity in the context of specific functions and of respecting the values and interests of older adults are emphasized.

  18. 15 CFR 241.1 - Capacities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Capacities. 241.1 Section 241.1... OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.1 Capacities. (a) The capacities of the standard barrel.../2 barrel 3,528 1.641 521/2 1/3 barrel 2,352 1.094 35 1 Struck measure. (b) The capacities of the...

  19. 15 CFR 241.1 - Capacities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Capacities. 241.1 Section 241.1... OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.1 Capacities. (a) The capacities of the standard barrel.../2 barrel 3,528 1.641 521/2 1/3 barrel 2,352 1.094 35 1 Struck measure. (b) The capacities of the...

  20. Use of a physiological profile to document motor impairment in ageing and in clinical groups.

    PubMed

    Lord, S R; Delbaere, K; Gandevia, S C

    2016-08-15

    Ageing decreases exercise performance and is frequently accompanied by reductions in cognitive performance. Deterioration in the physiological capacity to stand, locomote and exercise can manifest itself as falling over and represents a significant deterioration in sensorimotor control. In the elderly, falling leads to serious morbidity and mortality with major societal costs. Measurement of a suite of physiological capacities that are required for successful motor performance (including vision, muscle strength, proprioception and balance) has been used to produce a physiological profile assessment (PPA) which has been tracked over the age spectrum and in different diseases (e.g. multiple sclerosis, Parkinson's disease). As well as measures of specific physiological capacities, the PPA generates an overall 'score' which quantitatively measures an individual's cumulative risk of falling. The present review collates data from the PPA (and the physiological capacities it measures) as well as its use in strategies to reduce falls in the elderly and those with different diseases. We emphasise that (i) motor impairment arises via reductions in a wide range of sensorimotor abilities; (ii) the PPA approach not only gives a snapshot of the physiological capacity of an individual, but it also gives insight into the deficits among groups of individuals with particular diseases; and (iii) deficits in seemingly restricted and disparate physiological domains (e.g. vision, strength, cognition) are funnelled into impairments in tasks requiring upright balance. Motor impairments become more prevalent with ageing but careful physiological measurement and appropriate interventions offer a way to maximise health across the lifespan.

  1. Carrying capacity: maintaining outdoor recreation quality

    Treesearch

    David W. Lime; George H. Stankey

    1971-01-01

    A discussion of (1) what is meant by the concept of recreational carrying capacity; (2) what is known about capacities in terms of both how resources and experience of visitors are affected by recreational use; and (3) what alternative procedures the administrator can use to manage both resources and visitors for capacity.

  2. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  3. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  4. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  5. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  6. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  7. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  8. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  9. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  10. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  11. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  12. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  13. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Capacity. 574.410 Section 574.410... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which the grantee contracts to carry out an activity under this part has the capacity and capability to...

  14. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  15. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  16. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  17. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  18. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  19. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  20. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  1. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  2. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  3. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  4. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  5. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false Capacity. 574.410 Section 574.410... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which the grantee contracts to carry out an activity under this part has the capacity and capability to...

  6. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  7. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  8. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  9. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Capacity. 574.410 Section 574.410... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which the grantee contracts to carry out an activity under this part has the capacity and capability to...

  10. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  11. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  12. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  13. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... grant shall be made to provide reserve capacity for a project for secondary treatment or more stringent treatment or new interceptors and appurtenances. Grants for such projects shall be based on capacity... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA...

  14. Understanding Dimensions of Organizational Evaluation Capacity

    ERIC Educational Resources Information Center

    Bourgeois, Isabelle; Cousins, J. Bradley

    2013-01-01

    Organizational evaluation capacity building has been a topic of increasing interest in recent years. However, the actual dimensions of evaluation capacity have not been clearly articulated through empirical research. This study sought to address this gap by identifying the key dimensions of evaluation capacity in Canadian federal government…

  15. Compressibility and heat capacity of rotating plasma

    NASA Astrophysics Data System (ADS)

    Geyko, V. I.; Fisch, N. J.

    2017-02-01

    A rotating plasma column is shown to exhibit unusual heat capacity effects under compression. For near equilibrium thermodynamics and smooth wall conditions, the heat capacity depends on the plasma density, on the speed of the rotation, and on the mass ratio. For a certain range of parameters, the storage of energy in the electric field produces a significant increase in the heat capacity.

  16. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall...

  17. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall...

  18. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall...

  19. Rehabilitation Medicine Summit: Building Research Capacity

    ERIC Educational Resources Information Center

    Frontera, Walter R.; Fuhrer, Marcus J.; Jette, Alan M.; Chan, Leighton; Cooper, Rory A.; Duncan, Pamela W.; Kemp, John D.; Ottenbacher, Kenneth J.; Peckham, P. Hunter; Roth, Elliot J.; Tate, Denise G.

    2006-01-01

    The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The 5 elements of research capacity that guided the discussions were (a) researchers; (b) research culture, environment, and infrastructure;…

  20. 25 CFR 167.6 - Carrying capacities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Carrying capacities. 167.6 Section 167.6 Indians BUREAU... Carrying capacities. (a) The Commissioner of Indian Affairs on June 26, 1943, promulgated the authorized carrying capacity for each land management district of the Navajo Reservation. (b) Recommended adjustments...