The Effects of Teacher-Student Small Talk on Out-of-Seat Behavior

ERIC Educational Resources Information Center

Patterson, Steven T.

2009-01-01

This paper presents the results of a function-based study initiated by a general education teacher to reduce a general education student's out-of-seat behavior. Procedures included direct observation, data collection, functional behavior assessment using a Functional Assessment Protocol (FAP; Schroeder, n.d.), hypothesis development, and creating…

Automatic numerical evaluation of vacancy-mediated transport for arbitrary crystals: Onsager coefficients in the dilute limit using a Green function approach

NASA Astrophysics Data System (ADS)

Trinkle, Dallas R.

2017-10-01

A general solution for vacancy-mediated diffusion in the dilute-vacancy/dilute-solute limit for arbitrary crystal structures is derived from the master equation. A general numerical approach to the vacancy lattice Green function reduces to the sum of a few analytic functions and numerical integration of a smooth function over the Brillouin zone for arbitrary crystals. The Dyson equation solves for the Green function in the presence of a solute with arbitrary but finite interaction range to compute the transport coefficients accurately, efficiently and automatically, including cases with very large differences in solute-vacancy exchange rates. The methodology takes advantage of the space group symmetry of a crystal to reduce the complexity of the matrix inversion in the Dyson equation. An open-source implementation of the algorithm is available, and numerical results are presented for the convergence of the integration error of the bare vacancy Green function, and tracer correlation factors for a variety of crystals including wurtzite (hexagonal diamond) and garnet.

Phenotypes in defined genotypes including siblings with Usher syndrome.

PubMed

Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Andréasson, Sten

2011-06-01

To characterize visual function in defined genotypes including siblings with Usher syndrome. Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

Some Aspects of Thermal Transport across the Interface between Graphene and Epoxy in Nanocomposites.

PubMed

Wang, Yu; Yang, Chunhui; Pei, Qing-Xiang; Zhang, Yingyan

2016-03-01

Owing to the superior thermal properties of graphene, graphene-reinforced polymer nanocomposites hold great potential as the thermal interface materials (TIMs) dissipating heat for electronic packages. However, this application is greatly hindered by the high thermal resistance at the interface between graphene and polymer. In this paper, some important aspects of the improvement of the thermal transport across the interface between graphene and epoxy in graphene-epoxy nanocomposites, including the effectiveness of covalent and noncovalent functionalization, isotope doping, and acetylenic linkage in graphene are systematically investigated using molecular dynamics (MD) simulations. The simulation results show that the covalent and noncovalent functionalization techniques could considerably reduce the graphene-epoxy interfacial thermal resistance in the nanocomposites. Among different covalent functional groups, butyl is more effective than carboxyl and hydroxyl in reducing the interfacial thermal resistance. Different noncovalent functional molecules, including 1-pyrenebutyl, 1-pyrenebutyric acid, and 1-pyrenebutylamine, yield a similar amount of reductions. Moreover, it is found that the graphene-epoxy interfacial thermal resistance is insensitive to the carbon isotope doping in graphene, while it can be reduced moderately by replacing the sp(2) bonds in graphene with acetylenic linkages.

Nutritional intervention as part of functional rehabilitation in older people with reduced functional ability: a systematic review and meta-analysis of randomised controlled studies.

PubMed

Beck, A M; Dent, E; Baldwin, C

2016-12-01

Nutritional intervention is increasingly recognised as having an important role in functional rehabilitation for older people. Nonetheless, a greater understanding of the functional benefit of nutritional interventions is needed. A systematic review and meta-analysis examined randomised controlled trials (RCTs) published between 2007 and 2014 with the aim of determining whether nutritional intervention combined with rehabilitation benefited older people with reduced functional ability. Six electronic databases were searched. RCTs including people aged 65 years and older with reduced physical, social and/or cognitive function were included. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, and gradepro computer software (http://gradepro.org) was used for the quality assessment of critical and important outcomes. Included studies considered to be clinical homogenous were combined in a meta-analysis. Of the 788 studies screened, five were identified for inclusion. Nutritional intervention given with functional rehabilitation improved energy and protein intake, although it failed to provide any improvement in final body weight, hand-grip strength or muscle strength. There was no difference between groups in the critical outcomes; balance, cognition, activities of daily living and mortality at long-term follow-up. Nutritional intervention given with functional rehabilitation was associated with an increased likelihood of both mortality (odds ratio = 1.77; 95% confidence interval = 1.13-2.76) and hospitalisation (odds ratio = 2.29; 95% confidence interval = 1.10-4.79) during the intervention. Meta-analysis of the baseline data showed that, overall, the intervention cohort had a lower body weight and cognition. This meta-analysis highlights concerns regarding the quality of the randomisation of participants at baseline. Future high-quality research is essential to establish whether older people with loss of functional abilities can benefit from nutritional intervention. © 2016 The British Dietetic Association Ltd.

Donor predicted post-operative forced expiratory volume in one second predicts recipients' best forced expiratory volume in one second following size-reduced lung transplantation.

PubMed

Inci, Ilhan; Irani, Sarosh; Kestenholz, Peter; Benden, Christian; Boehler, Annette; Weder, Walter

2011-01-01

The limited number of available grafts is one of the major obstacles of lung transplantation. Size-reduced lung transplantation allows the use of oversized grafts for small recipients. Optimal lung size matching is vital to achieve best functional outcome and avoid potential problems when using oversized grafts. We hypothesise that donor-predicted postoperative forced expiratory volume in 1s (ppoFEV1) correlates with the recipient best FEV1 after size-reduced lung transplant, being useful for the estimation of function outcome. All patients undergoing size-reduced or standard bilateral lung transplantation were included (1992-2007). Donor ppoFEV1 was calculated and corrected with respect to size reduction and correlated with recipient measured best FEV1 post-transplant. In addition, pre- and postoperative clinical data including surgical complications and outcome of all size-reduced lung transplant recipients were compared with standard lung transplant recipients. A total of 61 size-reduced lung transplant recipients (lobar transplants, n=20; anatomic or non-anatomic resection, n=41) were included and compared to 145 standard transplants. The mean donor-recipient height difference was statistically significant between the two groups (p=0.0001). The mean donor ppoFEV1 was comparable with recipient best FEV1 (2.7±0.6 vs 2.6±0.7 l). There was a statistically significant correlation between donor ppoFEV1 and recipient best FEV1 (p=0.01, r=0.688). The 30-day mortality rate and 3-month, 1- and 5-year survival rates were comparable between the two groups. In size-reduced lung transplantation, postoperative recipient best FEV1 could be predicted from donor-calculated and corrected FEV1 with respect to its size reduction. Compared to standard lung transplantation, equivalent morbidity, mortality and functional results could be obtained after size-reduced lung transplantation. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Space Shuttle avionics upgrade - Issues and opportunities

NASA Astrophysics Data System (ADS)

Swaim, Richard A.; Wingert, William B.

An overview is conducted of existing Space Shuttle avionics and the possibilities for upgrading the cockpit to reduce costs and increase functionability. The current avionics include five general-purpose computers fitted with multifunction displays, dedicated switches and indicators, and dedicated flight instruments. The operational needs of the Shuttle are reviewed in the light of the avionics and potential upgrades in the form of microprocessors and display systems. The use of better processors can provide hardware support for multitasking and memory management and can reduce the life-cycle cost for software. Some limitations of the current technology are acknowledged including the Shuttle's power budget and structural configuration. A phased infusion of upgraded avionics is proposed that provides a functionally transparent replacement of crew-interface equipment as well as the addition of interface enhancements and the migration of selected functions.

Reduced functional connectivity within and between ‘social’ resting state networks in autism spectrum conditions

PubMed Central

Stoyanova, Raliza S.; Baron-Cohen, Simon; Calder, Andrew J.

2013-01-01

Individuals with Autism Spectrum Conditions (ASC) have difficulties in social interaction and communication, which is reflected in hypoactivation of brain regions engaged in social processing, such as medial prefrontal cortex (mPFC), amygdala and insula. Resting state studies in ASC have identified reduced connectivity of the default mode network (DMN), which includes mPFC, suggesting that other resting state networks incorporating ‘social’ brain regions may also be abnormal. Using Seed-based Connectivity and Group Independent Component Analysis (ICA) approaches, we looked at resting functional connectivity in ASC between specific ‘social’ brain regions, as well as within and between whole networks incorporating these regions. We found reduced functional connectivity within the DMN in individuals with ASC, using both ICA and seed-based approaches. Two further networks identified by ICA, the salience network, incorporating the insula and a medial temporal lobe network, incorporating the amygdala, showed reduced inter-network connectivity. This was underlined by reduced seed-based connectivity between the insula and amygdala. The results demonstrate significantly reduced functional connectivity within and between resting state networks incorporating ‘social’ brain regions. This reduced connectivity may result in difficulties in communication and integration of information across these networks, which could contribute to the impaired processing of social signals in ASC. PMID:22563003

Methods to reduce forest residue volume after timber harvesting and produce black carbon

Treesearch

Deborah S. Page-Dumroese; Matt D. Busse; James G. Archuleta; Darren McAvoy; Eric Roussel

2017-01-01

Forest restoration often includes thinning to reduce tree density and improve ecosystem processes and function while also reducing the risk of wildfire or insect and disease outbreaks. However, one drawback of these restoration treatments is that slash is often burned in piles that may damage the soil and require further restoration activities. Pile burning is...

Teacher-Conducted Trial-Based Functional Analyses as the Basis for Intervention

ERIC Educational Resources Information Center

Bloom, Sarah E.; Lambert, Joseph M.; Dayton, Elizabeth; Samaha, Andrew L.

2013-01-01

Previous studies have focused on whether a trial-based functional analysis (FA) yields the same outcomes as more traditional FAs, and whether interventions based on trial-based FAs can reduce socially maintained problem behavior. We included a full range of behavior functions and taught 3 teachers to conduct a trial-based FA with 3 boys with…

Fast Time-Dependent Density Functional Theory Calculations of the X-ray Absorption Spectroscopy of Large Systems.

PubMed

Besley, Nicholas A

2016-10-11

The computational cost of calculations of K-edge X-ray absorption spectra using time-dependent density functional (TDDFT) within the Tamm-Dancoff approximation is significantly reduced through the introduction of a severe integral screening procedure that includes only integrals that involve the core s basis function of the absorbing atom(s) coupled with a reduced quality numerical quadrature for integrals associated with the exchange and correlation functionals. The memory required for the calculations is reduced through construction of the TDDFT matrix within the absorbing core orbitals excitation space and exploiting further truncation of the virtual orbital space. The resulting method, denoted fTDDFTs, leads to much faster calculations and makes the study of large systems tractable. The capability of the method is demonstrated through calculations of the X-ray absorption spectra at the carbon K-edge of chlorophyll a, C 60 and C 70 .

Rehabilitation of patient with brachial plexus lesion and break in axillary artery. Case study.

PubMed

Bajuk, S; Jelnikar, T; Ortar, M

1996-01-01

This paper describes the physiotherapy and occupational therapy used in treating a 74-year-old woman with a left brachial plexus lesion, a break in the axillary artery, dislocation of the acromioclavicular joint, a broken scapula and clavicula, serial left rib fractures, and lacerations on the upper and lower arm. After testing the patient, the following goals were set: reduce pain, soften scar tissue, and improve joint motion, muscle strength, and functionality of the hand. A 12-month outpatient program was used. Various analgesics were used to reduce pain, and a special aid was made to unweight the shoulder and elbow joints. Physiotherapy included kinesiotherapy, audiovisual biofeedback, electrical stimulation, friction massage, and lymph drainage. Occupational therapy included active functional exercises and re-education. As a result of this program, the patient no longer had pain, passive range of motion was close to normal, active motion where present was improved, swelling was reduced, and the hand became functional again. Complex physiotherapy, occupational therapy, and the patient's motivation resulted in the rehabilitation of severe trauma of the hand.

Recent advances on edible films based on fruit and vegetables- a review

USDA-ARS?s Scientific Manuscript database

A food packaging system has different functions, including those related to containment, information, and marketing. However, its primary function is to separate food from the surrounding environment, reducing food exposure to deteriorating factors such as microorganisms, oxygen, water vapor, off-fl...

Aggression in autism spectrum disorder: presentation and treatment options

PubMed Central

Fitzpatrick, Sarah E; Srivorakiat, Laura; Wink, Logan K; Pedapati, Ernest V; Erickson, Craig A

2016-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent difficulties in social communication and social interaction, coupled with restricted, repetitive patterns of behavior or interest. Research indicates that aggression rates may be higher in individuals with ASD compared to those with other developmental disabilities. Aggression is associated with negative outcomes for children with ASD and their caregivers, including decreased quality of life, increased stress levels, and reduced availability of educational and social support. Therapeutic strategies including functional behavioral assessment, reinforcement strategies, and functional communication training may have a significant impact in reducing the frequency and intensity of aggressive behavior in individuals with ASD. Pharmacologic treatments, particularly the use of second-generation antipsychotics, may also be of some benefit in reducing aggression in individuals with ASD. With the ever-increasing rate of ASD diagnosis, development of effective therapeutic and pharmacologic methods for preventing and treating aggression are essential to improving outcomes in this disorder. PMID:27382295

Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

PubMed

Pahwa, R; Factor, S A; Lyons, K E; Ondo, W G; Gronseth, G; Bronte-Stewart, H; Hallett, M; Miyasaki, J; Stevens, J; Weiner, W J

2006-04-11

To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

New Era of Lipid-Lowering Drugs

PubMed Central

Rye, Kerry-Anne

2016-01-01

There are several established lipid-modifying agents, including statins, fibrates, niacin, and ezetimibe, that have been shown in randomized clinical outcome trials to reduce the risk of having an atherosclerotic cardiovascular event. However, in many people, the risk of having an event remains unacceptably high despite treatment with these established agents. This has stimulated the search for new therapies designed to reduce residual cardiovascular risk. New approaches that target atherogenic lipoproteins include: 1) inhibition of proprotein convertase subtilisin/kexin type 9 to increase removal of atherogenic lipoproteins from plasma; 2) inhibition of the synthesis of apolipoprotein (apo) B, the main protein component of atherogenic lipoproteins; 3) inhibition of microsomal triglyceride transfer protein to block the formation of atherogenic lipoproteins; 4) inhibition of adenosine triphosphate citrate lyase to inhibit the synthesis of cholesterol; 5) inhibition of the synthesis of lipoprotein(a), a factor known to cause atherosclerosis; 6) inhibition of apoC-III to reduce triglyceride-rich lipoproteins and to enhance high-density lipoprotein (HDL) functionality; and 7) inhibition of cholesteryl ester transfer protein, which not only reduces the concentration of atherogenic lipoproteins but also increases the level and function of the potentially antiatherogenic HDL fraction. Other new therapies that specifically target HDLs include infusions of reconstituted HDLs, HDL delipidation, and infusions of apoA-I mimetic peptides that mimic some of the functions of HDLs. This review describes the scientific basis and rationale for developing these new therapies and provides a brief summary of established therapies. PMID:26983688

Strength Analysis and Reliability Evaluation for Speed Reducers

NASA Astrophysics Data System (ADS)

Tsai, Yuo-Tern; Hsu, Yung-Yuan

2017-09-01

This paper studies the structural stresses of differential drive (DD) and harmonic drive (HD) for design improvement of reducers. The designed principles of the two reducers are reported for function comparison. The critical components of the reducers are constructed for performing motion simulation and stress analysis. DD is designed based on differential displacement of the decelerated gear ring as well as HD on a flexible spline. Finite element method (FEM) is used to analyze the structural stresses including the dynamic properties of the reducers. The stresses including kinematic properties of the two reducers are compared to observe the properties of the designs. The analyzed results are applied to identify the allowable loads of the reducers in use. The reliabilities of the reducers in different loads are further calculated according to the variation of stress. The studied results are useful on engineering analysis and reliability evaluation for designing a speed reducer with high ratios.

Elderly persons with ICU-acquired weakness: the potential role for β-hydroxy-β-methylbutyrate (HMB) supplementation?

PubMed

Rahman, Adam; Wilund, Kenneth; Fitschen, Peter J; Jeejeebhoy, Khursheed; Agarwala, Ravi; Drover, John W; Mourtzakis, Marina

2014-07-01

Intensive care unit (ICU)-acquired weakness is common and characterized by muscle loss, weakness, and paralysis. It is associated with poor short-term outcomes, including increased mortality, but the consequences of reduced long-term outcomes, including decreased physical function and quality of life, can be just as devastating. ICU-acquired weakness is particularly relevant to elderly patients who are increasingly consuming ICU resources and are at increased risk for ICU-acquired weakness and complications, including mortality. Elderly patients often enter critical illness with reduced muscle mass and function and are also at increased risk for accelerated disuse atrophy with acute illness. Increasingly, intensivists and researchers are focusing on strategies and therapies aimed at improving long-term neuromuscular function. β-Hydroxy-β-methylbutyrate (HMB), an ergogenic supplement, has shown efficacy in elderly patients and certain clinical populations in counteracting muscle loss. The present review discusses ICU-acquired weakness, as well as the unique physiology of muscle loss and skeletal muscle function in elderly patients, and then summarizes the evidence for HMB in elderly patients and in clinical populations. We subsequently postulate on the potential role and strategies in studying HMB in elderly ICU patients to improve muscle mass and function. © 2013 American Society for Parenteral and Enteral Nutrition.

Reduced representation bisulphite sequencing of the ten bovine somatic tissues reveals DNA methylation patterns

USDA-ARS?s Scientific Manuscript database

As a major component epigenetics, DNA methylation has been proved that widely functions in individual development and various diseases. It has been well studied in model organisms and human but includes limited data for the economic animals. Using reduced representation bisulphite sequencing (RRBS),...

Coal flow aids reduce coke plant operating costs and improve production rates

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

Bedard, R.A.; Bradacs, D.J.; Kluck, R.W.

2005-06-01

Chemical coal flow aids can provide many benefits to coke plants, including improved production rates, reduced maintenance and lower cleaning costs. This article discusses the mechanisms by which coal flow aids function and analyzes several successful case histories. 2 refs., 10 figs., 1 tab.

Implementing a Mobility Program to Minimize Post-Intensive Care Syndrome.

PubMed

Hopkins, Ramona O; Mitchell, Lorie; Thomsen, George E; Schafer, Michele; Link, Maggie; Brown, Samuel M

2016-01-01

Immobility in the intensive care unit (ICU) is associated with neuromuscular weakness, post-intensive care syndrome, functional limitations, and high costs. Early mobility-based rehabilitation in the ICU is feasible and safe. Mobility-based rehabilitation varied widely across 5 ICUs in 1 health care system, suggesting a need for continuous training and evaluation to maintain a strong mobility-based rehabilitation program. Early mobility-based rehabilitation shortens ICU and hospital stays, reduces delirium, and increases muscle strength and the ability to ambulate. Long-term effects include increased ability for self-care, faster return to independent functioning, improved physical function, and reduced hospital readmission and death. Factors that influence early mobility-based rehabilitation include having an interdisciplinary team; strong unit leadership; access to physical, occupational, and respiratory therapists; a culture focused on patient safety and quality improvement; a champion of early mobility; and a focus on measuring performance and outcomes.

Memory functioning in children with reading disabilities and/or attention deficit/hyperactivity disorder: a clinical investigation of their working memory and long-term memory functioning.

PubMed

Kibby, Michelle Y; Cohen, Morris J

2008-11-01

We examined memory functioning in children with reading disabilities (RD), Attention deficit/hyperactivity disorder (ADHD), and RD/ADHD using a clinic sample with a clinical instrument: the Children's Memory Scale, enhancing its generalizability. Participants included 23 children with RD, 30 with ADHD, 30 with RD/ADHD, and 30 controls. Children with RD presented with reduced verbal short-term memory (STM) but intact visual STM, central executive (CE), and long-term memory (LTM) functioning. Their deficit in STM appeared specific to tasks requiring phonetic coding of material. Children with ADHD displayed intact CE and LTM functioning but reduced visual-spatial STM, especially when off stimulant medication. Children with RD/ADHD had deficits consistent with both disorders.

Functional Neuro-Imaging and Post-Traumatic Olfactory Impairment

PubMed Central

Roberts, Richard J.; Sheehan, William; Thurber, Steven; Roberts, Mary Ann

2010-01-01

Objective: To evaluate via a research literature survey the anterior neurological significance of decreased olfactory functioning following traumatic brain injuries. Materials and Methods: A computer literature review was performed to locate all functional neuro-imaging studies on patients with post-traumatic anosmia and other olfactory deficits. Results: A convergence of findings from nine functional neuro-imaging studies indicating evidence for reduced metabolic activity at rest or relative hypo-perfusion during olfactory activations. Hypo-activation of the prefrontal regions was apparent in all nine post-traumatic samples, with three samples yielding evidence of reduced activity in the temporal regions as well. Conclusions: The practical ramifications include the reasonable hypothesis that a total anosmic head trauma patient likely has frontal lobe involvement. PMID:21716782

Subchronic Toluene Exposure alters Retinal Function in Long Evans Rats: Experimental Evidence Supporting Observations from Studies of Exposed Humans.

EPA Science Inventory

Studies of humans chronically exposed to volatile organic solvents commonly report impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports have been controversial, however, in part due to a lack of confirmation from controlled...

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

PubMed Central

Colon-Perez, Luis M; Tran, Kelvin; Thompson, Khalil; Pace, Michael C; Blum, Kenneth; Goldberger, Bruce A; Gold, Mark S; Bruijnzeel, Adriaan W; Setlow, Barry; Febo, Marcelo

2016-01-01

The abuse of ‘bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV. PMID:26997298

Combined reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease in sedentary elders with functional limitations

USDA-ARS?s Scientific Manuscript database

Objectives: Because they are potentially modifiable and may coexist, we evaluated the combined occurrence of a reduced forced expiratory volume in 1-second (FEV1) and peripheral artery disease (PAD), including its association with exertional symptoms, physical inactivity, and impaired mobility, in s...

Does psychological functioning mediate the relationship between bullying involvement and weight loss preoccupation in adolescents? A two-stage cross-sectional study.

PubMed

Lee, Kirsty; Guy, Alexa; Dale, Jeremy; Wolke, Dieter

2017-03-24

Adolescent bullying is associated with a range of adversities for those who are bullied i.e., victims and bully-victims (e.g., those who bully others and get victimised), including reduced psychological functioning and eating disorder symptoms. Bullies are generally well-adjusted psychologically, but previous research suggests that bullies may also engage in problematic diet behaviours. This study investigates a) whether adolescents involved in bullying (bullies, victims, bully-victims) are at increased risk of weight loss preoccupation, b) whether psychological functioning mediates this relationship and c) whether sex is a key moderator. A two-stage design was used. In stage 1, adolescents (n = 2782) from five UK secondary schools were screened for bullying involvement using self and peer reports. In stage 2, a sample of bullies, victims, bully-victims and uninvolved adolescents (n = 767) completed a battery of assessments. The measures included the eating behaviours component of the Child and Adolescent Psychiatric Assessment, which was reduced to one factor (weight loss preoccupation) and used as the outcome variable. Measures of self-esteem, body-esteem and emotional problems were reduced to a latent (mediator) variable of psychological functioning. Multi-group analysis examined the effects of sex and all models were adjusted for covariates (BMI, pubertal stage, age, parental education and ethnicity). Bullies, victims and bully-victims were at increased risk of weight loss preoccupation compared to adolescents uninvolved in bullying. The mechanism by which bullying involvement related to increased weight loss preoccupation varied by bullying role: in bullies the effect was direct, in victims the effect was indirect (via reduced psychological functioning) and in bully-victims the effect was both direct and indirect. Sex significantly moderated the relationship in bullies: weight loss preoccupation was only statistically significant in bullies who were boys. Bullying involvement during adolescence is associated with weight loss preoccupation. Bullies are likely driven by a desire to increase attractiveness and social status; whereas weight loss preoccupation in bullied adolescents may have maladaptive influences on diet and exercise behaviours due to its association with reduced psychological functioning. Future research should consider peer victimisation as a potential modifiable risk factor for reduced psychological functioning and weight loss preoccupation, which if targeted, may help to prevent maladaptive diet and exercise behaviours.

Neck pain and dysphagia associated to disc protrusion and reduced functional stability: A case report.

PubMed

Margelli, Michele; Vanti, Carla; Villafañe, Jorge Hugo; Andreotti, Roberto

2017-04-01

Deglutition dysfunction like dysphagia may be associated with cervical symptoms. A young female complained of pain on the neck and swallowing dysfunction that was reduced by means of isometric contraction of cervical muscles. Magnetic resonance imaging revealed an anterior C5-C6 disc protrusion associated with a lesion of the anterior longitudinal ligament. Barium radiograph showed a small anterior cervical osteophyte at C6 level and dynamic X-ray excluded anatomical instability. The treatment included manual therapy and active exercises to improve muscular stability. Diagnostic hypothesis was a combination of cervical disc dysfunction associated with C6 osteophyte and reduced functional stability. Copyright © 2016 Elsevier Ltd. All rights reserved.

A patient with heart failure and worsening kidney function.

PubMed

Sarnak, Mark J

2014-10-07

There is high prevalence of CKD, defined by reduced GFR, in patients with heart failure. Reduced kidney function is associated with increased morbidity and mortality in this patient population. The cardiorenal syndrome (CRS) involves a bidirectional relationship between the heart and kidneys whereby dysfunction in either may exacerbate the function of the other, but this syndrome has been difficult to precisely define because it has many complex physiologic, biochemical, and hormonal abnormalities. The pathophysiology of CRS is not completely understood, but potential mechanisms include reduced kidney perfusion due to decreased forward flow, increased right ventricular and venous pressure, and neurohormonal adaptations. Treatment options include inotropic medications; diuretics; ultrafiltration; and medications, such as β-blockers, inhibitors of the renin-angiotensin-aldosterone system, and more novel treatments that focus on unique aspects of the pathophysiology. Recent observational studies suggest that treatments that result in a decrease in venous pressure and lead to hemoconcentration may be associated with improved outcomes. Patients with CRS that is not responsive to medical interventions should be considered for ventricular assist devices, heart transplantation, or combined heart and kidney transplantation. Copyright © 2014 by the American Society of Nephrology.

Application of a Noise Adaptive Contrast Sensitivity Function to Image Data Compression

NASA Astrophysics Data System (ADS)

Daly, Scott J.

1989-08-01

The visual contrast sensitivity function (CSF) has found increasing use in image compression as new algorithms optimize the display-observer interface in order to reduce the bit rate and increase the perceived image quality. In most compression algorithms, increasing the quantization intervals reduces the bit rate at the expense of introducing more quantization error, a potential image quality degradation. The CSF can be used to distribute this error as a function of spatial frequency such that it is undetectable by the human observer. Thus, instead of being mathematically lossless, the compression algorithm can be designed to be visually lossless, with the advantage of a significantly reduced bit rate. However, the CSF is strongly affected by image noise, changing in both shape and peak sensitivity. This work describes a model of the CSF that includes these changes as a function of image noise level by using the concepts of internal visual noise, and tests this model in the context of image compression with an observer study.

Servo Reduces Friction In Flexure Bearing

NASA Technical Reports Server (NTRS)

Clingman, W. Dean

1991-01-01

Proposed servocontrol device reduces such resistive torques as stiction, friction, ripple, and cogging in flexure bearing described in LAR-14348, "Flexure Bearing Reduces Startup Friction". Reduces frictional "bump" torque encountered when bearing ball runs into buildup of grease on bearing race. Also used as cable follower to reduce torque caused by cable and hoses when they bend because of motion of bearing. New device includes torquer across ball race. Torquer controlled by servo striving to keep flexure at null, removing torque to outer ring. In effect, device is inner control loop reducing friction, but does not control platforms or any outer-control-loop functions.

Generalized wall function and its application to compressible turbulent boundary layer over a flat plate

NASA Astrophysics Data System (ADS)

Liu, J.; Wu, S. P.

2017-04-01

Wall function boundary conditions including the effects of compressibility and heat transfer are improved for compressible turbulent boundary flows. Generalized wall function formulation at zero-pressure gradient is proposed based on coupled velocity and temperature profiles in the entire near-wall region. The parameters in the generalized wall function are well revised. The proposed boundary conditions are integrated into Navier-Stokes computational fluid dynamics code that includes the shear stress transport turbulence model. Numerical results are presented for a compressible boundary layer over a flat plate at zero-pressure gradient. Compared with experimental data, the computational results show that the generalized wall function reduces the first grid spacing in the directed normal to the wall and proves the feasibility and effectivity of the generalized wall function method.

Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.

PubMed

Won, Hyejung; Lee, Hye-Ryeon; Gee, Heon Yung; Mah, Won; Kim, Jae-Ick; Lee, Jiseok; Ha, Seungmin; Chung, Changuk; Jung, Eun Suk; Cho, Yi Sul; Park, Sae-Geun; Lee, Jung-Soo; Lee, Kyungmin; Kim, Daesoo; Bae, Yong Chul; Kaang, Bong-Kiun; Lee, Min Goo; Kim, Eunjoon

2012-06-13

Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.

The Impact of a Participatory Care Model on Work Satisfaction of Care Workers and the Functionality, Connectedness, and Mental Health of Community-Dwelling Older People.

PubMed

Bernoth, Maree; Burmeister, Oliver K; Morrison, Mark; Islam, Md Zahidul; Onslow, Fiona; Cleary, Michelle

2016-06-01

This study describes and evaluates an innovative program designed to reduce functional decline among seniors, using a participatory care approach and integrated health teams. The evaluation provides older people and community support workers (CSWs) with the opportunity to share their experiences of being involved with an innovative program to reduce functional decline (mobility, skin integrity, nutrition, mental health, continence) of older, community dwelling adults implemented by a Nursing Service in a major capital city in Australia. As part of the program, CSWs were trained to provide care that aimed to reduce functional decline, and improve the quality of life for the care recipients. Data were collected through in-depth interviews with older people receiving care and a focus group (FG) was conducted with CSWs. Seven themes emerged during data analysis: 1) functionality/independence; 2) prevention; 3) confidence; 4) connection; 5) the approach; 6) care plans; and 7) the role of the CSWs. The relationship built between care giver and receiver and the mutual respect facilitated through adopting a participatory care approach was crucial. This relationship-focused care contributed to improved functionality and consequently quality of life for the older person, and for the CSW professional it contributed to their development, improved satisfaction with their role, and increased pride in the difference they make in the lives of their clients. Opportunities for improvement of the program included ensuring that participants understood the rationale for all aspects of the program, including regular reminders, as well as the use of regular reviews of individual outcomes.

Exercise interventions in polypathological aging patients that coexist with diabetes mellitus: improving functional status and quality of life.

PubMed

Cadore, Eduardo Lusa; Izquierdo, Mikel

2015-06-01

In elderly populations, diabetes is associated with reduced muscle strength, poor muscle quality, and accelerated loss of muscle mass. In addition, diabetes mellitus increases risk for accelerated aging and for the development of frailty syndrome. This disease is also associated with a polypathological condition, and its complications progressively affect quality of life and survival. Exercise interventions, including resistance training, represent the cornerstones of diabetes management, especially in patients at severe functional decline. This review manuscript aimed to describe the beneficial effects of different exercise interventions on the functional capacity of elderly diabetics, including those at polypathological condition. The SciELO, Science Citation Index, MEDLINE, Scopus, SPORTDiscus, and ScienceDirect databases were searched from 1980 to 2015 for articles published from original scientific investigations. In addition to the beneficial effects of exercise interventions on glycemic control, and on the cardiovascular risk factors associated with diabetes, physical exercise is an effective intervention to improve muscle strength, power output, and aerobic power and functional capacity in elderly diabetic patients. Thus, a combination of resistance and endurance training is the most effective exercise intervention to promote overall physical fitness in these patients. In addition, in diabetic patients with frailty and severe functional decline, a multicomponent exercise program including strength and power training, balance exercises, and gait retraining may be an effective intervention to reduce falls and improve functional capacity and quality of life in these patients.

Alleviating Autonomic Dysreflexia after Spinal Cord Injury

DTIC Science & Technology

2017-12-01

autonomic disorders greatly influence the functional, psychological , and socioeconomic aspects of patients’ lives. Compared to numer- ous...The disruption of descending autonomic pathways renders abnormalities in multiple organ systems including cardiovascular function, respiration...the rise in blood pressure, the integration center in the brainstem transmits signals to the heart via parasympathetic pathways to reduce the heart

Family Ranching and Farming: A Consensus Management Model to Improve Family Functioning and Decrease Work Stress.

ERIC Educational Resources Information Center

Zimmerman, Toni Schindler; Fetsch, Robert J.

1994-01-01

Notes that internal and external threats could squeeze ranch and farm families out of business. Offers six-step Consensus Management Model that combines strategic planning with psychoeducation/family therapy. Describes pilot test with intergenerational ranch family that indicated improvements in family functioning, including reduced stress and…

26 CFR 53.4940-1 - Excise tax on net investment income.

Code of Federal Regulations, 2013 CFR

2013-04-01

... this section) and the capital gain net income (net capital gain for taxable years beginning before... to the basis for determining gain, or section 362(c). Thus, a private foundation must reduce the cost... charitable function shall be no greater than the income earned from such function which is includible as...

26 CFR 53.4940-1 - Excise tax on net investment income.

Code of Federal Regulations, 2012 CFR

2012-04-01

... this section) and the capital gain net income (net capital gain for taxable years beginning before... to the basis for determining gain, or section 362(c). Thus, a private foundation must reduce the cost... charitable function shall be no greater than the income earned from such function which is includible as...

26 CFR 53.4940-1 - Excise tax on net investment income.

Code of Federal Regulations, 2011 CFR

2011-04-01

... this section) and the capital gain net income (net capital gain for taxable years beginning before... to the basis for determining gain, or section 362(c). Thus, a private foundation must reduce the cost... charitable function shall be no greater than the income earned from such function which is includible as...

26 CFR 53.4940-1 - Excise tax on net investment income.

Code of Federal Regulations, 2010 CFR

2010-04-01

... this section) and the capital gain net income (net capital gain for taxable years beginning before... to the basis for determining gain, or section 362(c). Thus, a private foundation must reduce the cost... charitable function shall be no greater than the income earned from such function which is includible as...

26 CFR 53.4940-1 - Excise tax on net investment income.

Code of Federal Regulations, 2014 CFR

2014-04-01

... this section) and the capital gain net income (net capital gain for taxable years beginning before... to the basis for determining gain, or section 362(c). Thus, a private foundation must reduce the cost... charitable function shall be no greater than the income earned from such function which is includible as...

A Biobehavioral Approach to the Treatment of Functional Encopresis in Children

ERIC Educational Resources Information Center

Friman, Patrick C.; Hofstadter, Kristi L.; Jones, Kevin M.

2006-01-01

Functional encopresis (FE) refers to the repeated passage of feces into inappropriate places at least once per month for at least 3 months. Treatment of FE targets the processes that cause or exacerbate the condition, including reduced colonic motility, constipation, and fecal impaction. The cardinal elements of successful treatment include…

The control of translational accuracy is a determinant of healthy ageing in yeast

PubMed Central

Leadsham, Jane E.; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S.; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F.; Gourlay, Campbell W.

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. PMID:28100667

The control of translational accuracy is a determinant of healthy ageing in yeast.

PubMed

von der Haar, Tobias; Leadsham, Jane E; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F; Gourlay, Campbell W

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. © 2017 The Authors.

Effectiveness of interventions to reduce ordering of thyroid function tests: a systematic review.

PubMed

Zhelev, Zhivko; Abbott, Rebecca; Rogers, Morwenna; Fleming, Simon; Patterson, Anthea; Hamilton, William Trevor; Heaton, Janet; Thompson Coon, Jo; Vaidya, Bijay; Hyde, Christopher

2016-06-03

To evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests. Systematic review. MEDLINE, EMBASE and the Cochrane Database up to May 2015. We included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions. 2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used. 27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics. The results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified. CRD42014006192. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effectiveness of interventions to reduce ordering of thyroid function tests: a systematic review

PubMed Central

Abbott, Rebecca; Rogers, Morwenna; Fleming, Simon; Patterson, Anthea; Hamilton, William Trevor; Heaton, Janet; Vaidya, Bijay; Hyde, Christopher

2016-01-01

Objectives To evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests. Design Systematic review. Data sources MEDLINE, EMBASE and the Cochrane Database up to May 2015. Eligibility criteria for selecting studies We included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions. Study appraisal and synthesis methods 2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used. Results 27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics. Conclusions The results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified. Trial registration number CRD42014006192. PMID:27259523

78 FR 76190 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

... received will advance three objectives: (i) reduce reporting burdens; (ii) ensure that it organizes.... FRA will summarize comments received in response to this notice in a subsequent notice and include... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

Fibrinogen Availability and Coagulation Function After Hemorrhage and Resuscitation in Pigs

DTIC Science & Technology

2011-08-01

Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to...that reduced clot formation rate and clot strength by ROTEM are indicative of transfusion re- quirements (14). The purpose of this study was to inves...administration and to reduce the usage of blood products (15,16). In this study, we observed a parallel changing pattern between fibrinogen concentration

Improved functions and reduced length of stay after inpatient rehabilitation programs in older adults with stroke: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Bindawas, Saad M; Vennu, Vishal; Moftah, Emad

2017-01-01

to examine the effects of inpatient rehabilitation programs on function and length of stay in older adults with strokeMETHODS: A total of five electronic databases were searched for relevant randomized controlled trials that examined the effects of inpatient rehabilitation programs on functional recovery, as measured by the functional independence measure and length of stay, which was measured in days. We included full-text articles written in English, and no time limit. The methodological quality and risk of bias were assessed using the Physiotherapy Evidence Database Scale and the Cochrane collaboration tools respectively. The effect sizes and confidence intervals were estimated using fixed-effect modelsRESULTS: Eight randomized controlled trials involving 1,910 patients with stroke were included in the meta-analysis showed that patients who participated in the inpatient rehabilitation programs had significantly (p less than 0.05) higher functional independence measure scores (effect size = 0.10; 95 percent confidence interval = 0.01, 0.22) and shorter length of stay (effect size = 0.14; 95 percent confidence interval = 0.03, 0.22). This systematic review provided evidence that inpatient rehabilitation programs have beneficial effects, improving functionality and reducing length of stay for older adults with stroke.

Complex functionality with minimal computation: Promise and pitfalls of reduced-tracer ocean biogeochemistry models

NASA Astrophysics Data System (ADS)

Galbraith, Eric D.; Dunne, John P.; Gnanadesikan, Anand; Slater, Richard D.; Sarmiento, Jorge L.; Dufour, Carolina O.; de Souza, Gregory F.; Bianchi, Daniele; Claret, Mariona; Rodgers, Keith B.; Marvasti, Seyedehsafoura Sedigh

2015-12-01

Earth System Models increasingly include ocean biogeochemistry models in order to predict changes in ocean carbon storage, hypoxia, and biological productivity under climate change. However, state-of-the-art ocean biogeochemical models include many advected tracers, that significantly increase the computational resources required, forcing a trade-off with spatial resolution. Here, we compare a state-of-the art model with 30 prognostic tracers (TOPAZ) with two reduced-tracer models, one with 6 tracers (BLING), and the other with 3 tracers (miniBLING). The reduced-tracer models employ parameterized, implicit biological functions, which nonetheless capture many of the most important processes resolved by TOPAZ. All three are embedded in the same coupled climate model. Despite the large difference in tracer number, the absence of tracers for living organic matter is shown to have a minimal impact on the transport of nutrient elements, and the three models produce similar mean annual preindustrial distributions of macronutrients, oxygen, and carbon. Significant differences do exist among the models, in particular the seasonal cycle of biomass and export production, but it does not appear that these are necessary consequences of the reduced tracer number. With increasing CO2, changes in dissolved oxygen and anthropogenic carbon uptake are very similar across the different models. Thus, while the reduced-tracer models do not explicitly resolve the diversity and internal dynamics of marine ecosystems, we demonstrate that such models are applicable to a broad suite of major biogeochemical concerns, including anthropogenic change. These results are very promising for the further development and application of reduced-tracer biogeochemical models that incorporate "sub-ecosystem-scale" parameterizations.

Including All Staff in an Alternative School's Effort to Reduce Violence

ERIC Educational Resources Information Center

Waterman, Stephanie J.; Burstyn, Joan N.

2008-01-01

Interview data from non-teaching staff at Garfield alternative school revealed how the entire staff-including custodians, secretaries, and hall monitors-contributed to the success of the school's violence prevention efforts. The school functioned democratically: non-teaching staff attended violence prevention workshops offered to all staff; the…

Effects of Flavonoid-Containing Beverages and EGCG on Endothelial Function

PubMed Central

Shenouda, Sherene M.; Vita, Joseph A.

2009-01-01

Abnormalities of the vascular endothelium contribute to all stages of atherosclerosis from lesion development to clinical cardiovascular disease events. Recognized risk factors, including diabetes mellitus, hypertension, dyslipidemia, cigarette smoking, and sedentary lifestyle are associated with endothelial dysfunction. A variety of pharmacological and behavioral interventions have been shown to reverse endothelial dysfunction in patients with cardiovascular disease. A large number of epidemiological studies suggest that dietary factors, including increased intake of flavonoid-containing foods and beverages, reduce cardiovascular risk, and recent studies have shown that such beverages have favorable effects on endothelial function. These studies have engendered interest in the development of dietary supplements or drugs that would allow for more convenient and higher dose administration of flavonoids and might prove useful for prevention or treatment of cardiovascular disease. In this paper, we will review the contribution of endothelial dysfunction to the pathogenesis and clinical expression of atherosclerosis and recent data linking flavonoid and EGCG consumption to improved endothelial function and reduced cardiovascular risk. PMID:17906190

Atypicalities in cortical structure, handedness, and functional lateralization for language in autism spectrum disorders.

PubMed

Lindell, Annukka K; Hudry, Kristelle

2013-09-01

Language is typically a highly lateralized function, with atypically reduced or reversed lateralization linked to language impairments. Given the diagnostic and prognostic role of impaired language for autism spectrum disorders (ASDs), this paper reviews the growing body of literature that examines patterns of lateralization in individuals with ASDs. Including research from structural and functional imaging paradigms, and behavioral evidence from investigations of handedness, the review confirms that atypical lateralization is common in people with ASDs. The evidence indicates reduced structural asymmetry in fronto-temporal language regions, attenuated functional activation in response to language and pre-linguistic stimuli, and more ambiguous (mixed) hand preferences, in individuals with ASDs. Critically, the evidence emphasizes an intimate relationship between atypical lateralization and language impairment, with more atypical asymmetries linked to more substantive language impairment. Such evidence highlights opportunities for the identification of structural and functional biomarkers of ASDs, affording the potential for earlier diagnosis and intervention implementation.

A Val85Met Mutation in Melanocortin-1 Receptor Is Associated with Reductions in Eumelanic Pigmentation and Cell Surface Expression in Domestic Rock Pigeons (Columba livia)

PubMed Central

Guernsey, Michael W.; Ritscher, Lars; Miller, Matthew A.; Smith, Daniel A.; Schöneberg, Torsten; Shapiro, Michael D.

2013-01-01

Variation in the melanocortin-1 receptor (Mc1r) is associated with pigmentation diversity in wild and domesticated populations of vertebrates, including several species of birds. Among domestic bird species, pigmentation variation in the rock pigeon ( Columba livia ) is particularly diverse. To determine the potential contribution of Mc1r variants to pigment diversity in pigeons, we sequenced Mc1r in a wide range of pigeon breeds and identified several single nucleotide polymorphisms, including a variant that codes for an amino acid substitution (Val85Met). In contrast to the association between Val85Met and eumelanism in other avian species, this change was associated with pheomelanism in pigeons. In vitro cAMP accumulation and protein expression assays revealed that Val85Met leads to decreased receptor function and reduced cell surface expression of the mutant protein. The reduced in vitro function is consistent with the observed association with reduced eumelanic pigmentation. Comparative genetic and cellular studies provide important insights about the range of mechanisms underlying diversity among vertebrates, including different phenotypic associations with similar mutations in different species. PMID:23977400

Is there a neuroanatomical basis of the vulnerability to suicidal behavior? A coordinate-based meta-analysis of structural and functional MRI studies

PubMed Central

van Heeringen, Kees; Bijttebier, Stijn; Desmyter, Stefanie; Vervaet, Myriam; Baeken, Chris

2014-01-01

Objective: We conducted meta-analyses of functional and structural neuroimaging studies comparing adolescent and adult individuals with a history of suicidal behavior and a psychiatric disorder to psychiatric controls in order to objectify changes in brain structure and function in association with a vulnerability to suicidal behavior. Methods: Magnetic resonance imaging studies published up to July 2013 investigating structural or functional brain correlates of suicidal behavior were identified through computerized and manual literature searches. Activation foci from 12 studies encompassing 475 individuals, i.e., 213 suicide attempters and 262 psychiatric controls were subjected to meta-analytical study using anatomic or activation likelihood estimation (ALE). Result: Activation likelihood estimation revealed structural deficits and functional changes in association with a history of suicidal behavior. Structural findings included reduced volumes of the rectal gyrus, superior temporal gyrus and caudate nucleus. Functional differences between study groups included an increased reactivity of the anterior and posterior cingulate cortices. Discussion: A history of suicidal behavior appears to be associated with (probably interrelated) structural deficits and functional overactivation in brain areas, which contribute to a decision-making network. The findings suggest that a vulnerability to suicidal behavior can be defined in terms of a reduced motivational control over the intentional behavioral reaction to salient negative stimuli. PMID:25374525

Electrochemical sensor having suspended element counter electrode and deflection method for current sensing

DOEpatents

Thundat, Thomas G.; Brown, Gilbert M.

2010-05-18

An electrochemical suspended element-based sensor system includes a solution cell for holding an electrolyte comprising solution including at least one electrochemically reducible or oxidizable species. A working electrode (WE), reference electrode (RE) and a counter electrode (CE) are disposed in the solution. The CE includes an asymmetric suspended element, wherein one side of the suspended element includes a metal or a highly doped semiconductor surface. The suspended element bends when current associated with reduction or oxidation of the electrochemically reducible or oxidizable species at the WE passes through the suspended element. At least one measurement system measures the bending of the suspended element or a parameter which is a function of the bending.

Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology

PubMed Central

Hüttemann, Maik; Lee, Icksoo; Gao, Xiufeng; Pecina, Petr; Pecinova, Alena; Liu, Jenney; Aras, Siddhesh; Sommer, Natascha; Sanderson, Thomas H.; Tost, Monica; Neff, Frauke; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Naton, Beatrix; Rathkolb, Birgit; Rozman, Jan; Favor, Jack; Hans, Wolfgang; Prehn, Cornelia; Puk, Oliver; Schrewe, Anja; Sun, Minxuan; Höfler, Heinz; Adamski, Jerzy; Bekeredjian, Raffi; Graw, Jochen; Adler, Thure; Busch, Dirk H.; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Weissmann, Norbert; Doan, Jeffrey W.; Bassett, David J. P.; Grossman, Lawrence I.

2012-01-01

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (−50 and −29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced Penh and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (−12%), reduced total oxygen consumption rate (−8%), improved glucose tolerance, and reduced grip force (−14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction and thus reduced airway responsiveness; long-term lung pathology develops in the knockout mice due to impairment of energy-costly lung maintenance processes; and therefore, we propose mitochondrial oxidative phosphorylation as a novel target for the treatment of respiratory diseases, such as asthma.—Hüttemann, M., Lee, I., Gao, X., Pecina, P., Pecinova, A., Liu, J., Aras, S., Sommer, N., Sanderson, T. H., Tost, M., Neff, F., Aguilar-Pimentel, J. A., Becker, L., Naton, B., Rathkolb, B., Rozman, J., Favor, J., Hans, W., Prehn, C., Puk, O., Schrewe, A., Sun, M., Höfler, H., Adamski, J., Bekeredjian, R., Graw, J., Adler, T., Busch, D. H., Klingenspor, M., Klopstock, T., Ollert, M., Wolf, E., Fuchs, H., Gailus-Durner, V., Hrabě de Angelis, M., Weissmann, N., Doan, J. W., Bassett, D. J. P., Grossman, L. I. Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology. PMID:22730437

Factors associated with quality of life and caregiver strain amongst frail older adults referred to a community rehabilitation service: implications for service delivery.

PubMed

Comans, Tracy A; Currin, Michelle L; Brauer, Sandra G; Haines, Terry P

2011-01-01

To identify factors contributing to reduced quality of life and increased caregiver strain in an older population referred to a community rehabilitation team and to recommend service delivery models. Analytical cross-sectional study arising from baseline assessments from 107 subjects drawn from a randomised controlled trial of community rehabilitation service delivery models. A community rehabilitation team based in Brisbane, Queensland, Australia. Primary outcome variables include quality of life (EQ-5D & VAS) and Carer Strain Index. Predictor variables include participation in functional activities, history of falls, number of medications, number of co-morbidities, depression, environmental hazards, physical function and nutrition. Association between variables assessed using linear regression. Major factors contributing to reduced quality of life were having reduced participation in daily activities, depression, and having poor vision. Having poor nutrition and no longer driving also contributed to poor quality of life. The major factor contributing to increased caregiver strain was reduced participation in daily activities by the older person. Community rehabilitation services working with older populations must adopt models of care that screen for and address a wide range of factors that contribute to poor quality of life and caregiver strain.

Reduction of vibration by using mechatronical subsystem

NASA Astrophysics Data System (ADS)

Białas, K.; Buchacz, A.

2015-11-01

The primary aim introduced in this paper is synthesis of mechatronical system understand as planning of this type of systems. Mechatronical system is consisted of fundamental mechanical system and subsystem reducing vibration including electric elements. Fundamental system is received applying reverse task of dynamic (synthesis) and it's including inertial and elastic elements. The subsystem includes electric elements by means moving-coil transducer. The synthesis can also be used to change the already existing systems. Due to the method, introduced in this work, may be performed as early as whilst the designing of future functions. Using this way of designing is support for designers of mechanical systems with active reducing of vibrations.

Stromal interaction molecules 1 and 2 are key regulators of autoreactive T cell activation in murine autoimmune central nervous system inflammation.

PubMed

Schuhmann, Michael K; Stegner, David; Berna-Erro, Alejandro; Bittner, Stefan; Braun, Attila; Kleinschnitz, Christoph; Stoll, Guido; Wiendl, Heinz; Meuth, Sven G; Nieswandt, Bernhard

2010-02-01

Calcium (Ca(2+)) signaling in T lymphocytes is essential for a variety of functions, including the regulation of differentiation, gene transcription, and effector functions. A major Ca(2+) entry pathway in nonexcitable cells, including T cells, is store-operated Ca(2+) entry (SOCE), wherein depletion of intracellular Ca(2+) stores upon receptor stimulation causes subsequent influx of extracellular Ca(2+) across the plasma membrane. Stromal interaction molecule (STIM) 1 is the Ca(2+) sensor in the endoplasmic reticulum, which controls this process, whereas the other STIM isoform, STIM2, coregulates SOCE. Although the contribution of STIM molecules and SOCE to T lymphocyte function is well studied in vitro, their significance for immune processes in vivo has remained largely elusive. In this study, we studied T cell function in mice lacking STIM1 or STIM2 in a model of myelin-oligodendrocyte glycoprotein (MOG(35-55))-induced experimental autoimmune encephalomyelitis (EAE). We found that STIM1 deficiency significantly impaired the generation of neuroantigen-specific T cell responses in vivo with reduced Th1/Th17 responses, resulting in complete protection from EAE. Mice lacking STIM2 developed EAE, but the disease course was ameliorated. This was associated with a reduced clinical peak of disease. Deficiency of STIM2 was associated with an overall reduced proliferative capacity of lymphocytes and a reduction of IFN-gamma/IL-17 production by neuroantigen-specific T cells. Neither STIM1 nor STIM2 deficiency altered the phenotype or function of APCs. These findings reveal a crucial role of STIM-dependent pathways for T cell function and activation under autoimmune inflammatory conditions, establishing them as attractive new molecular therapeutic targets for the treatment of inflammatory and autoimmune disorders.

Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders

PubMed Central

Woodward, Neil D.; Heckers, Stephan

2015-01-01

Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537

Factors associated with reduced functional outcome and quality of life in patients having limb-sparing surgery for soft tissue sarcomas - a national multicenter study of 128 patients.

PubMed

Saebye, Casper; Fugloe, Hanna M; Nymark, Tine; Safwat, Akmal; Petersen, Michael M; Baad-Hansen, Thomas; Krarup-Hansen, Anders; Keller, Johnny

2017-02-01

Limb-sparing surgery for sarcomas has become possible in most cases. However, the impact of the procedure on the functional outcome has only been investigated in a few studies. The aim of this study has been to identify tumor- and patient-related factors associated with reduced functional outcome and quality of life after limb-sparing surgery in soft tissue sarcoma patients. In total, 128 patients (mean age = 58, female/male = 54/74) who were treated with limb-sparing surgery without bone resection for soft tissue sarcomas in Denmark during the period 1 January 2009 to 31 December 2011 were included. Patients were asked to participate at least one year after surgery, and patients who had experienced local recurrence or metastatic disease were excluded. The Toronto Extremity Salvage Score (TESS) measured functional disability, while the Musculoskeletal Tumor Society Score (MSTS) measured functional impairment. European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 measured quality of life. Tumor- and patient-related factors (age, gender, tumor depth, tumor size, malignancy, comorbidity, location, and radiotherapy) were extracted from the Danish National Sarcoma Database. Wilcoxon rank-sum test and Kruskal-Wallis were used for univariable analysis. Adjusted odds ratios were estimated by using multiple logistic regression models. In the multiple regression analysis, it was found that female gender (p = 0.03), lower extremity tumors (p < 0.01) and radiotherapy (p = 0.02) resulted in an increased risk of a lower TESS score. Initial reduced postoperative function was found to be associated with a lower functional outcome. Patients with reduced functional outcome have increased risk for reduced quality of life (p < 0.01). The results of this study show that patient- and tumor-related factors have an important role in the functional outcome.

The Role of Executive Functions in the Control of Aggressive Behavior

PubMed Central

Krämer, Ulrike M.; Kopyciok, Robert P. J.; Richter, Sylvia; Rodriguez-Fornells, Antoni; Münte, Thomas F.

2011-01-01

An extensive literature suggests a link between executive functions and aggressive behavior in humans, pointing mostly to an inverse relationship, i.e., increased tendencies toward aggression in individuals scoring low on executive function tests. This literature is limited, though, in terms of the groups studied and the measures of executive functions. In this paper, we present data from two studies addressing these issues. In a first behavioral study, we asked whether high trait aggressiveness is related to reduced executive functions. A sample of over 600 students performed in an extensive behavioral test battery including paradigms addressing executive functions such as the Eriksen Flanker task, Stroop task, n-back task, and Tower of London (TOL). High trait aggressive participants were found to have a significantly reduced latency score in the TOL, indicating more impulsive behavior compared to low trait aggressive participants. No other differences were detected. In an EEG-study, we assessed neural and behavioral correlates of error monitoring and response inhibition in participants who were characterized based on their laboratory-induced aggressive behavior in a competitive reaction time task. Participants who retaliated more in the aggression paradigm and had reduced frontal activity when being provoked did not, however, show any reduction in behavioral or neural correlates of executive control compared to the less aggressive participants. Our results question a strong relationship between aggression and executive functions at least for healthy, high-functioning people. PMID:21747775

Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin-Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia.

PubMed

Cabrera-Pastor, Andrea; Llansola, Marta; Felipo, Vicente

2016-12-21

Extracellular protein kinases, including cAMP-dependent protein kinase (PKA), modulate neuronal functions including N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation. NMDA receptor activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO), which activates guanylate cyclase, increasing cGMP, which is released to the extracellular fluid, allowing analysis of this glutamate-NO-cGMP pathway in vivo by microdialysis. The function of this pathway is impaired in hyperammonemic rats. The aims of this work were to assess (1) whether the glutamate-NO-cGMP pathway is modulated in cerebellum in vivo by an extracellular PKA, (2) the role of phosphorylation and activity of calcium/calmodulin-dependent protein kinase II (CaMKII) and NOS in the pathway modulation by extracellular PKA, and (3) whether the effects are different in hyperammonemic and control rats. The pathway was analyzed by in vivo microdialysis. The role of extracellular PKA was analyzed by inhibiting it with a membrane-impermeable inhibitor. The mechanisms involved were analyzed in freshly isolated cerebellar slices from control and hyperammonemic rats. In control rats, inhibiting extracellular PKA reduces the glutamate-NO-cGMP pathway function in vivo. This is due to reduction of CaMKII phosphorylation and activity, which reduces NOS phosphorylation at Ser1417 and NOS activity, resulting in reduced guanylate cyclase activation and cGMP formation. In hyperammonemic rats, under basal conditions, CaMKII phosphorylation and activity are increased, increasing NOS phosphorylation at Ser847, which reduces NOS activity, guanylate cyclase activation, and cGMP. Inhibiting extracellular PKA in hyperammonemic rats normalizes CaMKII phosphorylation and activity, NOS phosphorylation, NOS activity, and cGMP, restoring normal function of the pathway.

Lung volumes, ventricular function and pulmonary arterial flow in children operated on for left-sided congenital diaphragmatic hernia: long-term results.

PubMed

Abolmaali, Nasreddin; Koch, Arne; Götzelt, Knut; Hahn, Gabriele; Fitze, Guido; Vogelberg, Christian

2010-07-01

To compare MRI-based functional pulmonary and cardiac measurements in the long-term follow-up of children operated on for left-sided congenital diaphragmatic hernia (CDH) with age- and body size-matched healthy controls. Twelve children who received immediate postnatal surgery for closure of isolated left-sided CDH were included and received basic medical examinations, pulmonary function testing and echocardiography. MRI included measurement of lung volume, ventricular function assessment and velocity-encoded imaging of the pulmonary arteries and was compared with the data for 12 healthy children matched for age and body size. While patients' clinical test results were not suspicious, comparison between the MRI data for patients and those for healthy controls revealed significant differences. In patients, the volumes of the left lungs were increased and the tidal volume was larger on the right side. While the stroke volumes of both ventricles were reduced, heart rate and ejection fraction were increased. Flow, acceleration time and cross-sectional area of the left pulmonary artery were reduced. Functional MRI detected pulmonary and cardiac findings in the late follow-up of CDH children which may be missed by standard clinical methods and might be relevant for decisions regarding late outcome and treatment.

Gender Differences in the Association of Individual and Contextual Exposures with Lung Function in a Rural Canadian Population.

PubMed

Janzen, Bonnie; Karunanayake, Chandima; Rennie, Donna; Pickett, William; Lawson, Joshua; Kirychuk, Shelley; Hagel, Louise; Senthilselvan, Ambikaipakan; Koehncke, Niels; Dosman, James; Pahwa, Punam

2017-02-01

To investigate the association of individual and contextual exposures with lung function by gender in rural-dwelling Canadians. A cross-sectional mail survey obtained completed questionnaires on exposures from 8263 individuals; a sub-sample of 1609 individuals (762 men, 847 women) additionally participated in clinical lung function testing. The three dependent variables were forced expired volume in one second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC ratio. Independent variables included smoking, waist circumference, body mass index, indoor household exposures (secondhand smoke, dampness, mold, musty odor), occupational exposures (grain dust, pesticides, livestock, farm residence), and socioeconomic status. The primary analysis was multiple linear regression, conducted separately for each outcome. The potential modifying influence of gender was tested in multivariable models using product terms between gender and each independent variable. High-risk waist circumference was related to reduced FVC and FEV 1 for both genders, but the effect was more pronounced in men. Greater pack-years smoking was associated with lower lung function values. Exposure to household smoke was related to reduced FEV 1 , and exposure to livestock, with increased FEV 1 . Lower income adequacy was associated with reduced FVC and FEV 1 . High-risk waist circumference was more strongly associated with reduced lung function in men than women. Longitudinal research combined with rigorous exposure assessment is needed to clarify how sex and gender interact to impact lung function in rural populations.

Complex functionality with minimal computation. Promise and pitfalls of reduced-tracer ocean biogeochemistry models

DOE PAGES

Galbraith, Eric D.; Dunne, John P.; Gnanadesikan, Anand; ...

2015-12-21

Earth System Models increasingly include ocean biogeochemistry models in order to predict changes in ocean carbon storage, hypoxia, and biological productivity under climate change. However, state-of-the-art ocean biogeochemical models include many advected tracers, that significantly increase the computational resources required, forcing a trade-off with spatial resolution. Here, we compare a state-of the art model with 30 prognostic tracers (TOPAZ) with two reduced-tracer models, one with 6 tracers (BLING), and the other with 3 tracers (miniBLING). The reduced-tracer models employ parameterized, implicit biological functions, which nonetheless capture many of the most important processes resolved by TOPAZ. All three are embedded inmore » the same coupled climate model. Despite the large difference in tracer number, the absence of tracers for living organic matter is shown to have a minimal impact on the transport of nutrient elements, and the three models produce similar mean annual preindustrial distributions of macronutrients, oxygen, and carbon. Significant differences do exist among the models, in particular the seasonal cycle of biomass and export production, but it does not appear that these are necessary consequences of the reduced tracer number. With increasing CO2, changes in dissolved oxygen and anthropogenic carbon uptake are very similar across the different models. Thus, while the reduced-tracer models do not explicitly resolve the diversity and internal dynamics of marine ecosystems, we demonstrate that such models are applicable to a broad suite of major biogeochemical concerns, including anthropogenic change. Lastly, these results are very promising for the further development and application of reduced-tracer biogeochemical models that incorporate ‘‘sub-ecosystem-scale’’ parameterizations.« less

Dry cupping for plantar fasciitis: a randomized controlled trial.

PubMed

Ge, Weiqing; Leson, Chelsea; Vukovic, Corey

2017-05-01

[Purpose] The purpose of this study was to determine the effects of dry cupping on pain and function of patients with plantar fasciitis. [Subjects and Methods] Twenty-nine subjects (age 15 to 59 years old, 20 females and 9 males), randomly assigned into the two groups (dry cupping therapy and electrical stimulation therapy groups), participated in this study. The research design was a randomized controlled trial (RCT). Treatments were provided to the subjects twice a week for 4 weeks. Outcome measurements included the Visual Analogue Pain Scale (VAS) (at rest, first in the morning, and with activities), the Foot and Ankle Ability Measure (FAAM), the Lower Extremity Functional Scale (LEFS), as well as the pressure pain threshold. [Results]The data indicated that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function significantly in the population tested, as all the 95% Confidence Intervals (CIs) did not include 0 except for the pressure pain threshold. There was no significant difference between the dry cupping therapy and electrical stimulation groups in all the outcome measurements. [Conclusion] These results support that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function in the population tested.

Dry cupping for plantar fasciitis: a randomized controlled trial

PubMed Central

Ge, Weiqing; Leson, Chelsea; Vukovic, Corey

2017-01-01

[Purpose] The purpose of this study was to determine the effects of dry cupping on pain and function of patients with plantar fasciitis. [Subjects and Methods] Twenty-nine subjects (age 15 to 59 years old, 20 females and 9 males), randomly assigned into the two groups (dry cupping therapy and electrical stimulation therapy groups), participated in this study. The research design was a randomized controlled trial (RCT). Treatments were provided to the subjects twice a week for 4 weeks. Outcome measurements included the Visual Analogue Pain Scale (VAS) (at rest, first in the morning, and with activities), the Foot and Ankle Ability Measure (FAAM), the Lower Extremity Functional Scale (LEFS), as well as the pressure pain threshold. [Results]The data indicated that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function significantly in the population tested, as all the 95% Confidence Intervals (CIs) did not include 0 except for the pressure pain threshold. There was no significant difference between the dry cupping therapy and electrical stimulation groups in all the outcome measurements. [Conclusion] These results support that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function in the population tested. PMID:28603360

Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia.

PubMed

Panickar, Kiran S; Jang, Saebyeol

2013-08-01

Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, energy failure, free radical production, excitotoxicity, altered calcium homeostasis, and activation of proteases all of which affect brain functioning and also contribute to longterm disabilities including cognitive decline. Inflammation, mitochondrial dysfunction, increased oxidative/nitrosative stress, and intracellular calcium overload contribute to brain injury including cell death and brain edema. However, there is a paucity of agents that can effectively reduce cerebral damage and hence considerable attention has focused on developing newer agents with more efficacy and fewer side-effects. Polyphenols are natural compounds with variable phenolic structures and are rich in vegetables, fruits, grains, bark, roots, tea, and wine. Most polyphenols have antioxidant, anti-inflammatory, and anti-apoptotic properties and their protective effects on mitochondrial functioning, glutamate uptake, and regulating intracellular calcium levels in ischemic injury in vitro have been demonstrated. This review will assess the current status of the potential effects of polyphenols in reducing cerebral injury and improving cognitive function in ischemia in animal and human studies. In addition, the review will also examine available patents in nutrition and agriculture that relates to cerebral ischemic injury with an emphasis on plant polyphenols.

Rehabilitation in multiple sclerosis.

PubMed

Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

2017-07-01

The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

Reconstruction of facial nerve injuries in children.

PubMed

Fattah, Adel; Borschel, Gregory H; Zuker, Ron M

2011-05-01

Facial nerve trauma is uncommon in children, and many spontaneously recover some function; nonetheless, loss of facial nerve activity leads to functional impairment of ocular and oral sphincters and nasal orifice. In many cases, the impediment posed by facial asymmetry and reduced mimetic function more significantly affects the child's psychosocial interactions. As such, reconstruction of the facial nerve affords great benefits in quality of life. The therapeutic strategy is dependent on numerous factors, including the cause of facial nerve injury, the deficit, the prognosis for recovery, and the time elapsed since the injury. The options for treatment include a diverse range of surgical techniques including static lifts and slings, nerve repairs, nerve grafts and nerve transfers, regional, and microvascular free muscle transfer. We review our strategies for addressing facial nerve injuries in children.

CHOLINE PARTIALLY PREVENTS THE IMPACT OF ETHANOL ON THE LIPID RAFT DEPENDENT FUNCTIONS OF L1 CELL ADHESION MOLECULE

PubMed Central

Tang, Ningfeng; Bamford, Penny; Jones, Jace; He, Min; Kane, Maureen A.; Mooney, Sandra M.; Bearer, Cynthia F.

2014-01-01

Background Fetal Alcohol Spectrum Disorder, the leading known cause of mental retardation, is caused by alcohol exposure during pregnancy. One mechanism of ethanol teratogenicity is the disruption of the function of L1 cell adhesion molecule (L1). These functions include enhancement of neurite outgrowth, trafficking through lipid rafts, and signal transduction. Recent data have shown that choline supplementation of rat pups reduces the effects of ethanol on neurobehavior. We sought to determine if choline could prevent the effect of ethanol on L1 function using a simple experimental system. Methods Cerebellar granule neurons (CGN) from postnatal day 6 rat pups were cultured with and without supplemental choline, and the effects on L1 signaling, lipid raft distribution and neurite outgrowth were measured in the presence or absence of ethanol. Results Choline significantly reduced the effect of ethanol on L1 signaling, the distribution of L1 in lipid rafts and L1 mediated neurite outgrowth. However, choline supplemented ethanol exposed cultures remained significantly different than controls. Conclusions Choline pretreatment of CGN significantly reduces the disruption of L1 function by ethanol, but does not completely return L1 function to baseline. This experimental system will enable discovery of the mechanism of the neuroprotective effect of choline. PMID:25421509

Usability Testing of the BRANCH Smartphone App Designed to Reduce Harmful Drinking in Young Adults.

PubMed

Milward, Joanna; Deluca, Paolo; Drummond, Colin; Watson, Rod; Dunne, Jacklyn; Kimergård, Andreas

2017-08-08

Electronic screening and brief intervention (eSBI) apps demonstrate potential to reduce harmful drinking. However, low user engagement rates with eSBI reduce overall effectiveness of interventions. As "Digital Natives," young adults have high expectations of app quality. Ensuring that the design, content, and functionality of an eSBI app are acceptable to young adults is an integral stage to the development process. The objective of this study was to identify usability barriers and enablers for an app, BRANCH, targeting harmful drinking in young adults. The BRANCH app contains a drinking diary, alcohol reduction goal setting functions, normative drinking feedback, and information on risks and advice for cutting down. The app includes a social feature personalized to motivate cutting down and to promote engagement with a point-based system for usage. Three focus groups were conducted with 20 users who had tested the app for 1 week. A detailed thematic analysis was undertaken. The first theme, "Functionality" referred to how users wanted an easy-to-use interface, with minimum required user-input. Poor functionality was considered a major usability barrier. The second theme, "Design" described how an aesthetic with minimum text, clearly distinguishable tabs and buttons and appealing infographics was integral to the level of usability. The final theme, "Content" described how participants wanted all aspects of the app to be automatically personalized to them, as well as providing them with opportunities to personalize the app themselves, with increased options for social connectivity. There are high demands for apps such as BRANCH that target skilled technology users including young adults. Key areas to optimize eSBI app development that emerged from testing BRANCH with representative users include high-quality functionality, appealing aesthetics, and improved personalization. ©Joanna Milward, Paolo Deluca, Colin Drummond, Rod Watson, Jacklyn Dunne, Andreas Kimergård. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.08.2017.

Differential effects of power training versus functional task practice on compensation and restoration of arm function after stroke.

PubMed

Corti, Manuela; McGuirk, Theresa E; Wu, Samuel S; Patten, Carolynn

2012-09-01

Improved upper-extremity (UE) movement with stroke rehabilitation may involve restoration of more normal or development of compensatory movement patterns. The authors investigated the differential effects of functional task practice (FTP) and dynamic resistance training (POWER) on clinical function and reaching kinematics in an effort to distinguish between mechanisms of gains. A total of 14 hemiparetic individuals were randomly assigned to 10 weeks of either FTP or POWER and then crossed over to 10 weeks of the alternate treatment. Treatment order A was FTP followed by POWER, whereas treatment order B was POWER followed by FTP. Evaluation before and after each treatment block included a battery of clinical evaluations and kinematics of paretic UE functional reach to grasp. Both FTP and POWER improved movement accuracy, as revealed by a shift toward normal, including fewer submovements and reduced reach-path ratio. However, active range of motion revealed differential treatment effects. Shoulder flexion and elbow extension decreased with FTP and were associated with increased trunk displacement. In contrast, shoulder flexion and elbow extension excursion increased with POWER and were associated with significantly reduced trunk displacement. Treatment order B (POWER followed by FTP) revealed greater overall improvements. FTP increases compensatory movement patterns to improve UE function. POWER leads to more normal movement patterns. POWER prior to FTP may enhance the benefits of repetitive task practice.

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

PubMed Central

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-01-01

Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF. PMID:27594875

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

PubMed

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-07-01

Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

Operational considerations to reduce solar array loads

NASA Technical Reports Server (NTRS)

Gerstenmaier, W.

1992-01-01

The key parameters associated with solar array plume loads are examined, and operational considerations aimed at minimizing the effect of the Shuttle plumes on the Space Station solar arrays are discussed. These include solar array pointing to reduce loads and restrictions on Shuttle piloting. Particular attention is given to the method used to obtain the forcing functions (thruster time firing histories) for solar array plume calculation.

Solution of the nonlinear mixed Volterra-Fredholm integral equations by hybrid of block-pulse functions and Bernoulli polynomials.

PubMed

Mashayekhi, S; Razzaghi, M; Tripak, O

2014-01-01

A new numerical method for solving the nonlinear mixed Volterra-Fredholm integral equations is presented. This method is based upon hybrid functions approximation. The properties of hybrid functions consisting of block-pulse functions and Bernoulli polynomials are presented. The operational matrices of integration and product are given. These matrices are then utilized to reduce the nonlinear mixed Volterra-Fredholm integral equations to the solution of algebraic equations. Illustrative examples are included to demonstrate the validity and applicability of the technique.

Solution of the Nonlinear Mixed Volterra-Fredholm Integral Equations by Hybrid of Block-Pulse Functions and Bernoulli Polynomials

PubMed Central

Mashayekhi, S.; Razzaghi, M.; Tripak, O.

2014-01-01

A new numerical method for solving the nonlinear mixed Volterra-Fredholm integral equations is presented. This method is based upon hybrid functions approximation. The properties of hybrid functions consisting of block-pulse functions and Bernoulli polynomials are presented. The operational matrices of integration and product are given. These matrices are then utilized to reduce the nonlinear mixed Volterra-Fredholm integral equations to the solution of algebraic equations. Illustrative examples are included to demonstrate the validity and applicability of the technique. PMID:24523638

Disrupted functional connectome in antisocial personality disorder.

PubMed

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2017-08-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD.

Disrupted functional connectome in antisocial personality disorder

PubMed Central

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen

2017-01-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD. PMID:27541949

Improved Blood Biomarkers but No Cognitive Effects from 16 Weeks of Multivitamin Supplementation in Healthy Older Adults

PubMed Central

Harris, Elizabeth; Macpherson, Helen; Pipingas, Andrew

2015-01-01

Supplementation with vitamins, minerals and phytonutrients may be beneficial for cognition, especially in older adults. The aim of this study was to assess the effects of multivitamin supplementation in older adults on cognitive function and associated blood biomarkers. In a randomised, double blind, placebo-controlled trial, healthy women (n = 68) and men (n = 48) aged 55–65 years were supplemented daily for 16 weeks with women’s and men’s formula multivitamin supplements. Assessments at baseline and post-supplementation included computerised cognitive tasks and blood biomarkers relevant to cognitive aging. No cognitive improvements were observed after supplementation with either formula; however, several significant improvements were observed in blood biomarkers including increased levels of vitamins B6 and B12 in women and men; reduced C-reactive protein in women; reduced homocysteine and marginally reduced oxidative stress in men; as well as improvements to the lipid profile in men. In healthy older people, multivitamin supplementation improved a number of blood biomarkers that are relevant to cognition, but these biomarker changes were not accompanied by improved cognitive function. PMID:25996285

Examining the use of HIT functions among physicians serving minority populations.

PubMed

Tarver, Will; Menachemi, Nir

2014-02-01

The Institute of Medicine highlighted the fact that the U.S. health care system does not provide consistent, high quality medical care to all people. The routine use of health information technology (HIT) that includes certain key functions may be critical in reducing such disparities. We used logistic regression analyses to examine differences when it comes to the routine use of key HIT functions that are linked to improvements in clinical care. Physicians predominantly serving Black patients were more likely than physicians predominantly serving White patients to routinely use HIT to generate reminders for clinicians and patients about preventive services. Similarly, physicians predominantly serving Hispanic patients were more likely than physicians predominantly serving White patients to routinely use HIT to access patients' preferred language. Importantly, although minority-serving institutions have lower adoption rates overall, differences exist in the routine use of key HIT functions that have the potential to reduce health disparities.

Reduced aspirin responsiveness as assessed by impedance aggregometry is not associated with adverse outcome after cardiac surgery in a small low-risk cohort.

PubMed

Bolliger, Daniel; Filipovic, Miodrag; Matt, Peter; Tanaka, Kenichi A; Gregor, Michael; Zenklusen, Urs; Seeberger, Manfred D; Lurati Buse, Giovanna

2016-01-01

Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate®) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) ≥300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test, p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128-2.585; p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate® platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery.

Cardiac function and cognition in older community-dwelling cardiac patients.

PubMed

Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

2017-11-01

Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

Factorization breaking of A d T for polarized deuteron targets in a relativistic framework

DOE PAGES

Jeschonnek, Sabine; Van Orden, J. W.

2017-04-17

We discuss the possible factorization of the tensor asymmetrymore » $$A^T_d$$ measured for polarized deuteron targets within a relativistic framework. We define a reduced asymmetry and find that factorization holds only in plane wave impulse approximation and if $p$-waves are neglected. Our numerical results show a strong factorization breaking once final state interactions are included. We also compare the $d$-wave content of the wave functions with the size of the factored, reduced asymmetry and find that there is no systematic relationship of this quantity to the d-wave probability of the various wave functions.« less

Non-functional Avionics Requirements

NASA Astrophysics Data System (ADS)

Paulitsch, Michael; Ruess, Harald; Sorea, Maria

Embedded systems in aerospace become more and more integrated in order to reduce weight, volume/size, and power of hardware for more fuel-effi ciency. Such integration tendencies change architectural approaches of system ar chi tec tures, which subsequently change non-functional requirements for plat forms. This paper provides some insight into state-of-the-practice of non-func tional requirements for developing ultra-critical embedded systems in the aero space industry, including recent changes and trends. In particular, formal requi re ment capture and formal analysis of non-functional requirements of avionic systems - including hard-real time, fault-tolerance, reliability, and per for mance - are exemplified by means of recent developments in SAL and HiLiTE.

Treating ADHD | NIH MedlinePlus the Magazine

MedlinePlus

... this page please turn JavaScript on. Feature: Understanding ADHD Treating ADHD Past Issues / Spring 2014 Table of Contents Currently available treatments aim at reducing the symptoms of ADHD and improving functioning. Treatments include medication, various types ...

Benefits of Exercise in Rheumatoid Arthritis

PubMed Central

Cooney, Jennifer K.; Law, Rebecca-Jane; Matschke, Verena; Lemmey, Andrew B.; Moore, Jonathan P.; Ahmad, Yasmeen; Jones, Jeremy G.; Maddison, Peter; Thom, Jeanette M.

2011-01-01

This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA) and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, “rheumatoid cachexia”. These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training. PMID:21403833

ACE Over Expression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer's Disease

PubMed Central

Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F.; Janjulia, Tea; Black, Keith L.; Shi, Peng D.; Gonzalez-Villalobos, Romer A.; Fuchs, Sebastien; Shen, Xiao Z.; Bernstein, Kenneth E.

2014-01-01

While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice over express ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD. PMID:24792094

Integrating QoS and security functions in an IP-VPN gateway

NASA Astrophysics Data System (ADS)

Fan, Kuo-Pao; Chang, Shu-Hsin; Lin, Kuan-Ming; Pen, Mau-Jy

2001-10-01

IP-based Virtual Private Network becomes more and more popular. It can not only reduce the enterprise communication cost but also increase the revenue of the service provider. The common IP-VPN application types include Intranet VPN, Extranet VPN, and remote access VPN. For the large IP-VPN market, some vendors develop dedicated IP-VPN devices; while some vendors add the VPN functions into their existing network equipment such as router, access gateway, etc. The functions in the IP-VPN device include security, QoS, and management. The common security functions supported are IPSec (IP Security), IKE (Internet Key Exchange), and Firewall. The QoS functions include bandwidth control and packet scheduling. In the management component, policy-based network management is under standardization in IETF. In this paper, we discuss issues on how to integrate the QoS and security functions in an IP-VPN Gateway. We propose three approaches to do this. They are (1) perform Qos first (2) perform IPSec first and (3) reserve fixed bandwidth for IPSec. We also compare the advantages and disadvantages of the three proposed approaches.

Maintaining ecosystem function and services in logged tropical forests.

PubMed

Edwards, David P; Tobias, Joseph A; Sheil, Douglas; Meijaard, Erik; Laurance, William F

2014-09-01

Vast expanses of tropical forests worldwide are being impacted by selective logging. We evaluate the environmental impacts of such logging and conclude that natural timber-production forests typically retain most of their biodiversity and associated ecosystem functions, as well as their carbon, climatic, and soil-hydrological ecosystem services. Unfortunately, the value of production forests is often overlooked, leaving them vulnerable to further degradation including post-logging clearing, fires, and hunting. Because logged tropical forests are extensive, functionally diverse, and provide many ecosystem services, efforts to expand their role in conservation strategies are urgently needed. Key priorities include improving harvest practices to reduce negative impacts on ecosystem functions and services, and preventing the rapid conversion and loss of logged forests. Copyright © 2014 Elsevier Ltd. All rights reserved.

Autistic spectrum disorders as functional disconnection syndrome.

PubMed

Melillo, Robert; Leisman, Gerry

2009-01-01

We outline the basis of how functional disconnection with reduced activity and coherence in the right hemisphere would explain all of the symptoms of autistic spectrum disorder as well as the observed increases in sympathetic activation. If the problem of autistic spectrum disorder is primarily one of desynchronization and ineffective interhemispheric communication, then the best way to address the symptoms is to improve coordination between areas of the brain. To do that the best approach would include multimodal therapeusis that would include a combination of somatosensory, cognitive, behavioral, and biochemical interventions all directed at improving overall health, reducing inflammation and increasing right hemisphere activity to the level that it becomes temporally coherent with the left hemisphere. We hypothesize that the unilateral increased hemispheric stimulation has the effect of increasing the temporal oscillations within the thalamocortical pathways bringing it closer to the oscillation rate of the adequately functioning hemisphere. We propose that increasing the baseline oscillation speed of one entire hemisphere will enhance the coordination and coherence between the two hemispheres allowing for enhanced motor and cognitive binding.

Picture This: Exploring the Lived Experience of High-Functioning Stroke Survivors Using Photovoice.

PubMed

Maratos, Marie; Huynh, Linh; Tan, Julia; Lui, Jordon; Jarus, Tal

2016-07-01

An increasing number of high-functioning stroke survivors are present with minimal functional impairments and are often discharged with reduced access to community reintegration. Our objectives were to explore the lived experience of high-functioning stroke survivors and to identify gaps in community and rehabilitation services. Photovoice was used with five high-functioning stroke survivors to photo-document their experiences. A modified inductive thematic analysis was used, and meanings behind the photographs were elicited through four focus group sessions followed by photography exhibitions. Five themes emerged: lack of understanding and consideration for persons with disability, emotional and behavioral impacts after stroke, self-reliance and dependence on others, importance of appropriate and accessible services, and financial determinants of quality of life. By including service users' voices; investing in adapted, community-based programs; and providing educational programs for creating attitudinal change among service providers, the polarization between who can and cannot access services will be reduced. © The Author(s) 2016.

Moderate perinatal thyroid hormone insufficiency alters visual system function in adult rats.

PubMed

Boyes, William K; Degn, Laura; George, Barbara Jane; Gilbert, Mary E

2018-04-21

Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction. Copyright © 2018. Published by Elsevier B.V.

How Does Subclinical Hyperthyroidism Affect Right Heart Function and Mechanics?

PubMed

Tadic, Marijana; Celic, Vera; Cuspidi, Cesare; Ilic, Sanja; Zivanovic, Vladimir; Marjanovic, Tamara

2016-02-01

Right heart function and mechanics have not been investigated in patients with subclinical hyperthyroidism. Our aim was to investigate right ventricular (RV) and right atrial (RA) function and deformation as evaluated by 3-dimensional echocardiography (3DE) and speckle-tracking 2-dimensional echocardiography (2DE) in these individuals. We included 39 untreated women with endogenous subclinical hyperthyroidism and 39 healthy women matched by age. All participants underwent laboratory analyses that included thyroid hormone levels and comprehensive 2DE and 3DE examinations. Three-dimensional echocardiographic RV volumes were significantly elevated in the patients with subclinical hyperthyroidism (P < .05), whereas the 3DE RV ejection fraction was reduced in this group, but with borderline significance. Two-dimensional echocardiographic longitudinal RV and RA strain were significantly reduced in the patients with subclinical hyperthyroidism. Two-dimensional echocardiographic RV systolic and early diastolic strain rates were reduced, whereas late diastolic strain rates were increased in the patients with subclinical hyperthyroidism. The same changes were detected in RA mechanics among the patients with subclinical hyperthyroidism. The thyrotropin (TSH) level correlated with the left ventricular mass index, transmitral early diastolic peak flow velocity (E)/late diastolic flow velocity (A) ratio, tricuspid E/A ratio, 2DE RV global strain, 2DE RA, strain, and 3DE RV end-diastolic volume. A multivariate regression analysis showed that the mitral E/A ratio, 2DE RV global strain, and 3DE RV end-diastolic volume were independently associated with the TSH level. Right ventricular and RA function as evaluated by 3DE and speckle-tracking 2DE is significantly impaired in patients with subclinical hyperthyroidism. The TSH level correlated with parameters for RV function and mechanics in the whole study population. © 2016 by the American Institute of Ultrasound in Medicine.

The Role of High-Density Lipoproteins in Reducing the Risk of Vascular Diseases, Neurogenerative Disorders, and Cancer

PubMed Central

McGrowder, Donovan; Riley, Cliff; Morrison, Errol Y. St. A.; Gordon, Lorenzo

2011-01-01

High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including “healthy” diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia. PMID:21490772

Implementation of Advanced Inventory Management Functionality in Automated Dispensing Cabinets

PubMed Central

Webb, Aaron; Lund, Jim

2015-01-01

Background: Automated dispensing cabinets (ADCs) are an integral component of distribution models in pharmacy departments across the country. There are significant challenges to optimizing ADC inventory management while minimizing use of labor and capital resources. The role of enhanced inventory control functionality is not fully defined. Objective: The aim of this project is to improve ADC inventory management by leveraging dynamic inventory standards and a low inventory alert platform. Methods: Two interventional groups and 1 historical control were included in the study. Each intervention group consisted of 6 ADCs that tested enhanced inventory management functionality. Interventions included dynamic inventory standards and a low inventory alert messaging system. Following separate implementation of each platform, dynamic inventory and low inventory alert systems were applied concurrently to all 12 ADCs. Outcome measures included number and duration of daily stockouts, ADC inventory turns, and number of phone calls related to stockouts received by pharmacy staff. Results: Low inventory alerts reduced both the number and duration of stockouts. Dynamic inventory standards reduced the number of daily stockouts without changing the inventory turns and duration of stockouts. No change was observed in number of calls related to stockouts made to pharmacy staff. Conclusions: Low inventory alerts and dynamic inventory standards are feasible mechanisms to help optimize ADC inventory management while minimizing labor and capital resources. PMID:26448672

Dietary Flavanols: A Review of Select Effects on Vascular Function, Blood Pressure, and Exercise Performance.

PubMed

Al-Dashti, Yousef A; Holt, Roberta R; Stebbins, Charles L; Keen, Carl L; Hackman, Robert M

2018-05-02

An individual's diet affects numerous physiological functions and can play an important role in reducing the risk of cardiovascular disease. Epidemiological and clinical studies suggest that dietary flavanols can be an important modulator of vascular risk. Diets and plant extracts rich in flavanols have been reported to lower blood pressure, especially in prehypertensive and hypertensive individuals. Flavanols may act in part through signaling pathways that affect vascular function, nitric oxide availability, and the release of endothelial-derived relaxing and constricting factors. During exercise, flavanols have been reported to modulate metabolism and respiration (e.g., maximal oxygen uptake, O 2 cost of exercise, and energy expenditure), and reduce oxidative stress and inflammation, resulting in increased skeletal muscle efficiency and endurance capacity. Flavanol-induced reductions in blood pressure during exercise may decrease the work of the heart. Collectively, these effects suggest that flavanols can act as an ergogenic aid to help delay the onset of fatigue. More research is needed to better clarify the effects of flavanols on vascular function, blood pressure regulation, and exercise performance and establish safe and effective levels of intake. Flavanol-rich foods and food products can be useful components of a healthy diet and lifestyle program for those seeking to better control their blood pressure or to enhance their physical activity. Key teaching points • Epidemiological and clinical studies indicate that dietary flavanols can reduce the risk of vascular disease. • Diets and plant extracts rich in flavanols have been reported to lower blood pressure and improve exercise performance in humans. • Mechanisms by which flavanols may reduce blood pressure function include alterations in signaling pathways that affect vascular function, nitric oxide availability, and the release of endothelial-derived relaxation and constriction factors. • Mechanisms by which flavanols may enhance exercise performance include modulation of metabolism and respiration (e.g., maximal oxygen uptake, O 2 cost of exercise, and energy expenditure) and reduction of oxidative stress and inflammation. These effects can result in increased skeletal muscle efficiency and endurance capacity. • Further research is needed to clarify the amount, timing, and frequency of flavanol intake for blood pressure regulation and exercise performance.

VISUAL FUNCTION CHANGES AFTER SUBCHRONIC TOLUENE INHALATION IN LONG-EVANS RATS.

EPA Science Inventory

Chronic exposure to volatile organic compounds, including toluene, has been associated with visual deficits such as reduced visual contrast sensitivity or impaired color discrimination in studies of occupational or residential exposure. These reports remain controversial, howeve...

Cognitive function and associated factors among older people in Taiwan: age and sex differences.

PubMed

Li, Cheng-Lun; Hsu, Hui-Chuan

2015-01-01

The aim of this study was to examine cognitive function and the risk and the protective factors by age and sex among Taiwanese older people. The data were from a nation-representative panel of older people in Taiwan. The participants completing both the 2003 and 2007 waves were included for analysis in this study (n=3228). Descriptive analysis and generalized linear model were applied, and the samples were stratified by age groups and by sex. The factors related to higher cognitive function at the intercept included being younger, male, higher education, and doing unpaid work. At the time slope, the age effect and physical function difficulties would reduce the cognitive function across time, while education and providing informational support would increase the cognitive function across time. There were age- and sex-differences in the factors related to cognitive function, particularly on the working status and social participation. Different health promotion strategies to target these populations should be accordingly developed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A Discrete Global Grid System Programming Language Using MapReduce

NASA Astrophysics Data System (ADS)

Peterson, P.; Shatz, I.

2016-12-01

A discrete global grid system (DGGS) is a powerful mechanism for storing and integrating geospatial information. As a "pixelization" of the Earth, many image processing techniques lend themselves to the transformation of data values referenced to the DGGS cells. It has been shown that image algebra, as an example, and advanced algebra, like Fast Fourier Transformation, can be used on the DGGS tiling structure for geoprocessing and spatial analysis. MapReduce has been shown to provide advantages for processing and generating large data sets within distributed and parallel computing. The DGGS structure is ideally suited for big distributed Earth data. We proposed that basic expressions could be created to form the atoms of a generalized DGGS language using the MapReduce programming model. We created three very efficient expressions: Selectors (aka filter) - A selection function that generate a set of cells, cell collections, or geometries; Calculators (aka map) - A computational function (including quantization of raw measurements and data sources) that generate values in a DGGS cell; and Aggregators (aka reduce) - A function that generate spatial statistics from cell values within a cell. We found that these three basic MapReduce operations along with a forth function, the Iterator, for horizontal and vertical traversing of any DGGS structure, provided simple building block resulting in very efficient operations and processes that could be used with any DGGS. We provide examples and a demonstration of their effectiveness using the ISEA3H DGGS on the PYXIS Studio.

Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response.

PubMed

Takatori, Osamu; Usui, Soichiro; Okajima, Masaki; Kaneko, Shuichi; Ootsuji, Hiroshi; Takashima, Shin-Ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Takamura, Masayuki

2017-05-01

The unfolded protein response (UPR) plays a pivotal role in ischemia-reperfusion (I/R) injury in various organs such as heart, brain, and liver. Sodium 4-phenylbutyrate (PBA) reportedly acts as a chemical chaperone that reduces UPR. In the present study, we evaluated the effect of PBA on reducing the UPR and protecting against myocardial I/R injury in mice. Male C57BL/6 mice were subjected to 30-minute myocardial I/R, and were treated with phosphate-buffered saline (as a vehicle) or PBA. At 4 hours after reperfusion, mice treated with PBA had reduced serum cardiac troponin I levels and numbers of apoptotic cells in left ventricles (LVs) in myocardial I/R. Infarct size had also reduced in mice treated with PBA at 48 hours after reperfusion. At 2 hours after reperfusion, UPR markers, including eukaryotic initiation of the factor 2α-subunit, activating transcription factor-6, inositol-requiring enzyme-1, glucose-regulated protein 78, CCAAT/enhancer-binding protein (C/EBP) homologous protein, and caspase-12, were significantly increased in mice treated with vehicle compared to sham-operated mice. Administration of PBA significantly reduced the I/R-induced increases of these markers. Cardiac function and dimensions were assessed at 21 days after I/R. Sodium 4-phenylbutyrate dedicated to the improvement of cardiac parameters deterioration including LV end-diastolic diameter and LV fractional shortening. Consistently, PBA reduced messenger RNA expression levels of cardiac remodeling markers such as collagen type 1α1, brain natriuretic peptide, and α skeletal muscle actin in LV at 21 days after I/R. Unfolded protein response mediates myocardial I/R injury. Administration of PBA reduces the UPR, apoptosis, infarct size, and preserved cardiac function. Hence, PBA may be a therapeutic option to attenuate myocardial I/R injury in clinical practice.

The problem of the treatment of sarcoidosis: Report of the Subcommittee on Therapy.

PubMed

Turiaf, J; Johns, C J; Terstein, A S; Tsuji, S; Wurm, K

1976-01-01

Stage I: Hilar Adenopathy With normal lung function observe, as it often resolves. With reduced lung function observe for 6-12 months. Treat if there is progression or persistence. With erythema nodosum use mild anti-inflammatory agents such as salicylates or like drugs. Stage II: Adenopathy + Pulmonar Infiltrates With normal or slightly reduced lung function observe; treat if it worsens. Treat if there is no remission in 6-12 months. With reduced lung function treat, possibly for many years or a lifetime. Stage III: Pulmonary Infiltrates +/- Fibrosis Without Adenopathy There is reduced lung function. Treat, demonstrate improvement, follow patients with serial measurements of vital capacity at least. Other Indications for Treatment Other indications for treatment include myocardial sarcoidosis, cerebral sarcoidosis (although the outcome is less certain), serious hepatic or renal sarcoidosis, hypercalcemia, persistent systemic symptoms, or other serious organ or functional impairment. Assess each patient individually and completely. Use good clinical judgement. It is clear that treatment that is too little or too late is of little benefit. Even the statistical results form a perfectly controlled study cannot provide absolute direction for the individual patient. As clinicians we are frequently called upon to apply considered judgements without hard data to predict the outcome. We also maintain the flexibility to change our therapeutic programs when circumstances change, either in the patient or in our knowledge. We can be grateful we have a treatment as good as corticosteroids and must try to exercise our best judgement as to when it should be instituted.

Bioreactor performance and functional gene analysis of microbial community in a limited-oxygen fed bioreactor for co-reduction of sulfate and nitrate with high organic input.

PubMed

Xu, Xi-jun; Chen, Chuan; Wang, Ai-jie; Yu, Hao; Zhou, Xu; Guo, Hong-liang; Yuan, Ye; Lee, Duu-jong; Zhou, Jizhong; Ren, Nan-qi

2014-08-15

Limited-oxygen mediated synergistic relationships between sulfate-reducing bacteria (SRB), nitrate-reducing bacteria (NRB) and sulfide-oxidizing bacteria (SOB, including nitrate-reducing, sulfide-oxidizing bacteria NR-SOB) were predicted to simultaneously remove contaminants of nitrate, sulfate and high COD, and eliminate sulfide generation. A lab-scale experiment was conducted to examine the impact of limited oxygen on these oxy-anions degradation, sulfide oxidation and associated microbial functional responses. In all scenarios tested, the reduction of both nitrate and sulfate was almost complete. When limited-oxygen was fed into bioreactors, S(0) formation was significantly improved up to ∼ 70%. GeoChip 4.0, a functional gene microarray, was used to determine the microbial gene diversity and functional potential for nitrate and sulfate reduction, and sulfide oxidation. The diversity of the microbial community in bioreactors was increased with the feeding of limited oxygen. Whereas the intensities of the functional genes involved in sulfate reduction did not show a significant difference, the abundance of the detected denitrification genes decreased in limited oxygen samples. More importantly, sulfide-oxidizing bacteria may alter their populations/genes in response to limited oxygen potentially to function more effectively in sulfide oxidation, especially to elemental sulfur. The genes fccA/fccB from nitrate-reducing, sulfide-oxidizing bacteria (NR-SOB), such as Paracoccus denitrificans, Thiobacillus denitrificans, Beggiatoa sp., Thiomicrospira sp., and Thioalkalivibrio sp., were more abundant under limited-oxygen condition. Copyright © 2014 Elsevier B.V. All rights reserved.

Foot orthoses for plantar heel pain: a systematic review and meta-analysis.

PubMed

Whittaker, Glen A; Munteanu, Shannon E; Menz, Hylton B; Tan, Jade M; Rabusin, Chantel L; Landorf, Karl B

2018-03-01

To investigate the effectiveness of foot orthoses for pain and function in adults with plantar heel pain. Systematic review and meta-analysis. The primary outcome was pain or function categorised by duration of follow-up as short (0 to 6 weeks), medium (7 to 12 weeks) or longer term (13 to 52 weeks). Medline, CINAHL, SPORTDiscus, Embase and the Cochrane Library from inception to June 2017. Studies must have used a randomised parallel-group design and evaluated foot orthoses for plantar heel pain. At least one outcome measure for pain or function must have been reported. A total of 19 trials (1660 participants) were included. In the short term , there was very low-quality evidence that foot orthoses do not reduce pain or improve function. In the medium term , there was moderate-quality evidence that foot orthoses were more effective than sham foot orthoses at reducing pain (standardised mean difference -0.27 (-0.48 to -0.06)). There was no improvement in function in the medium term. In the longer term , there was very low-quality evidence that foot orthoses do not reduce pain or improve function. A comparison of customised and prefabricated foot orthoses showed no difference at any time point. There is moderate-quality evidence that foot orthoses are effective at reducing pain in the medium term, however it is uncertain whether this is a clinically important change. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Novel cleavage of reductively aminated glycan-tags by N-bromosuccinimide to regenerate free, reducing glycans.

PubMed

Song, Xuezheng; Johns, Brian A; Ju, Hong; Lasanajak, Yi; Zhao, Chunmei; Smith, David F; Cummings, Richard D

2013-11-15

Glycans that are fluorescently tagged by reductive amination have been useful for functional glycomic studies. However, the existing tags can introduce unwanted properties to the glycans and complicate structural and functional studies. Here, we describe a facile method using N-bromosuccinimide (NBS) to remove the tags and efficiently regenerate free reducing glycans. The regenerated free reducing glycans can be easily analyzed by routine mass spectrometry or retagged with different tags for further studies. This new method can be used to efficiently remove a variety of fluorescent tags installed by reductive amination, including 2-aminobenzoic acid and 2-aminopyridine. NBS treatment essentially transforms the commonly used 2-aminobenzoic linkage to a cleavable linkage. It can be used to cleave printed glycans from microarrays and cleave neoglycopeptides containing a 2-aminobenzoic linker.

Novel cleavage of reductively aminated glycan-tags by N-bromosuccinimide to regenerate free, reducing glycans

PubMed Central

Song, Xuezheng; Johns, Brian A.; Ju, Hong; Lasanajak, Yi; Zhao, Chunmei; Smith, David F.; Cummings, Richard D.

2014-01-01

Glycans that are fluorescently tagged by reductive amination have been useful for functional glycomic studies. However, the existing tags can introduce unwanted properties to the glycans and complicate structural and functional studies. Here we describe a facile method using N-bromosuccinimide (NBS) to remove the tags and efficiently regenerate free reducing glycans. The regenerated free reducing glycans can be easily analyzed by routine mass spectrometry or re-tagged with different tags for further studies. This new method can be used to efficiently remove a variety of fluorescent tags installed by reductive amination, including 2-aminobenzoic acid and 2-aminopyridine. NBS treatment essentially transforms the commonly used 2-aminobenzoic linkage to a cleavable linkage. It can be used to cleave printed glycans from microarrays and cleave neoglycopeptides containing a 2-aminobenzoic linker. PMID:23992636

Attenuated anticorrelation between the default and dorsal attention networks with aging: evidence from task and rest.

PubMed

Spreng, R Nathan; Stevens, W Dale; Viviano, Joseph D; Schacter, Daniel L

2016-09-01

Anticorrelation between the default and dorsal attention networks is a central feature of human functional brain organization. Hallmarks of aging include impaired default network modulation and declining medial temporal lobe (MTL) function. However, it remains unclear if this anticorrelation is preserved into older adulthood during task performance, or how this is related to the intrinsic architecture of the brain. We hypothesized that older adults would show reduced within- and increased between-network functional connectivity (FC) across the default and dorsal attention networks. To test this hypothesis, we examined the effects of aging on task-related and intrinsic FC using functional magnetic resonance imaging during an autobiographical planning task known to engage the default network and during rest, respectively, with young (n = 72) and older (n = 79) participants. The task-related FC analysis revealed reduced anticorrelation with aging. At rest, there was a robust double dissociation, with older adults showing a pattern of reduced within-network FC, but increased between-network FC, across both networks, relative to young adults. Moreover, older adults showed reduced intrinsic resting-state FC of the MTL with both networks suggesting a fractionation of the MTL memory system in healthy aging. These findings demonstrate age-related dedifferentiation among these competitive large-scale networks during both task and rest, consistent with the idea that age-related changes are associated with a breakdown in the intrinsic functional architecture within and among large-scale brain networks. Copyright © 2016 Elsevier Inc. All rights reserved.

Transatrial Intrapericardial Tricuspid Annuloplasty

PubMed Central

Rogers, Toby; Ratnayaka, Kanishka; Sonmez, Merdim; Franson, Dominique N.; Schenke, William H.; Mazal, Jonathan R.; Kocaturk, Ozgur; Chen, Marcus Y.; Faranesh, Anthony Z.; Lederman, Robert J.

2015-01-01

OBJECTIVES This study sought to demonstrate transcatheter deployment of a circumferential device within the pericardial space to modify tricuspid annular dimensions interactively and to reduce functional tricuspid regurgitation (TR) in swine. BACKGROUND Functional TR is common and is associated with increased morbidity and mortality. There are no reported transcatheter tricuspid valve repairs. We describe a transcatheter extracardiac tricuspid annuloplasty device positioned in the pericardial space and delivered by puncture through the right atrial appendage. We demonstrate acute and chronic feasibility in swine. METHODS Transatrial intrapericardial tricuspid annuloplasty (TRAIPTA) was performed in 16 Yorkshire swine, including 4 with functional TR. Invasive hemodynamics and cardiac magnetic resonance imaging (MRI) were performed at baseline, immediately after annuloplasty and at follow-up. RESULTS Pericardial access via a right atrial appendage puncture was uncomplicated. In 9 naïve animals, tricuspid septal-lateral and anteroposterior dimensions, the annular area and perimeter, were reduced by 49%, 31%, 59%, and 24% (p < 0.001), respectively. Tricuspid leaflet coaptation length was increased by 53% (p < 0.001). Tricuspid geometric changes were maintained after 9.7 days (range, 7 to 14 days). Small effusions (mean, 46 ml) were observed immediately post-procedure but resolved completely at follow-up. In 4 animals with functional TR, severity of regurgitation by intracardiac echocardiography was reduced. CONCLUSIONS Transatrial intrapericardial tricuspid annuloplasty is a transcatheter extracardiac tricuspid valve repair performed by exiting the heart from within via a transatrial puncture. The geometry of the tricuspid annulus can interactively be modified to reduce severity of functional TR in an animal model. PMID:25703872

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

PubMed

Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

2009-12-01

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

Detection of reduced interhemispheric cortical communication during task execution in multiple sclerosis patients using functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Jimenez, Jon J.; Yang, Runze; Nathoo, Nabeela; Varshney, Vishal P.; Golestani, Ali-Mohammad; Goodyear, Bradley G.; Metz, Luanne M.; Dunn, Jeff F.

2014-07-01

Multiple sclerosis (MS) impairs brain activity through demyelination and loss of axons. Increased brain activity is accompanied by increases in microvascular hemoglobin oxygen saturation (oxygenation) and total hemoglobin, which can be measured using functional near-infrared spectroscopy (fNIRS). Due to the potentially reduced size and integrity of the white matter tracts within the corpus callosum, it may be expected that MS patients have reduced functional communication between the left and right sides of the brain; this could potentially be an indicator of disease progression. To assess interhemispheric communication in MS, we used fNIRS during a unilateral motor task and the resting state. The magnitude of the change in hemoglobin parameters in the motor cortex was significantly reduced in MS patients during the motor task relative to healthy control subjects. There was also a significant decrease in interhemispheric communication between the motor cortices (expressed as coherence) in MS patients compared to controls during the motor task, but not during the resting state. fNIRS assessment of interhemispheric coherence during task execution may be a useful marker in disorders with white matter damage or axonal loss, including MS.

Immune biomarkers in older adults: Role of physical activity.

PubMed

Valdiglesias, Vanessa; Sánchez-Flores, María; Maseda, Ana; Lorenzo-López, Laura; Marcos-Pérez, Diego; López-Cortón, Ana; Strasser, Barbara; Fuchs, Dietmar; Laffon, Blanca; Millán-Calenti, José C; Pásaro, Eduardo

2017-01-01

Aging is associated with a decline in the normal functioning of the immune system. Several studies described the relationship between immunological alterations, including immunosenescence and inflammation, and aging or age-related outcomes, such as sarcopenia, depression, and neurodegenerative disorders. Physical activity is known to improve muscle function and to exert a number of benefits on older adult health, including reduced risk for heart and metabolic system chronic diseases. However, the positive influence of physical activity on the immune system has not been elucidated. In order to shed light on the role of physical activity in immune responses of older individuals, a number of immunological parameters comprising % lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD19 + , and CD16 + 56 + ) and serum levels of neopterin and tryptophan metabolism products were evaluated in peripheral blood samples of older adults performing normal (N = 170) or reduced (N = 89) physical activity. In addition, the potential influence of other clinical and epidemiological factors was also considered. Results showed that subjects with reduced physical activity displayed significantly higher levels of CD4 + /CD8 + ratio, kynurenine/tryptophan ratio, and serum neopterin, along with lower %CD19 + cells and tryptophan concentrations. Further, some immunological biomarkers were associated with cognitive impairment and functional status. These data contribute to reinforce the postulation that physical activity supports healthy aging, particularly by helping to protect the immunological system from aging-related changes.

Identifying and reducing error in cluster-expansion approximations of protein energies.

PubMed

Hahn, Seungsoo; Ashenberg, Orr; Grigoryan, Gevorg; Keating, Amy E

2010-12-01

Protein design involves searching a vast space for sequences that are compatible with a defined structure. This can pose significant computational challenges. Cluster expansion is a technique that can accelerate the evaluation of protein energies by generating a simple functional relationship between sequence and energy. The method consists of several steps. First, for a given protein structure, a training set of sequences with known energies is generated. Next, this training set is used to expand energy as a function of clusters consisting of single residues, residue pairs, and higher order terms, if required. The accuracy of the sequence-based expansion is monitored and improved using cross-validation testing and iterative inclusion of additional clusters. As a trade-off for evaluation speed, the cluster-expansion approximation causes prediction errors, which can be reduced by including more training sequences, including higher order terms in the expansion, and/or reducing the sequence space described by the cluster expansion. This article analyzes the sources of error and introduces a method whereby accuracy can be improved by judiciously reducing the described sequence space. The method is applied to describe the sequence-stability relationship for several protein structures: coiled-coil dimers and trimers, a PDZ domain, and T4 lysozyme as examples with computationally derived energies, and SH3 domains in amphiphysin-1 and endophilin-1 as examples where the expanded pseudo-energies are obtained from experiments. Our open-source software package Cluster Expansion Version 1.0 allows users to expand their own energy function of interest and thereby apply cluster expansion to custom problems in protein design. © 2010 Wiley Periodicals, Inc.

The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging.

PubMed

Panickar, Kiran S; Jewell, Dennis E

2015-08-01

Aging in humans is associated with chronic low-grade inflammation (systemic), and this condition is sometimes referred to as "inflammaging". In general, canines also age similarly to humans, and such aging is associated with a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Each of these conditions is also associated with an increase in pro-inflammatory cytokines. An inflammatory state characterized by an increase in pro-inflammatory markers including but not restricted to tumor necrosis factor-α, interleukin-6, IL-1β, and C-reactive protein (CRP) is believed to contribute to or worsen a general decline in biological mechanisms responsible for physical function with aging. Nutritional management of inflammation in aging dogs is important in maintaining health. In particular, natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and, when included in the diet, may contribute to a reduction in inflammation. While there are scientific data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals, the clinical data are limited and more studies are needed to validate the efficacy of these ingredients. This review will summarize the role of dietary ingredients in reducing inflammatory molecules as well as review the evidence available to support the role of diet and nutrition in reducing chronic low-grade systemic inflammation in animal and human studies with a special reference to canines, where possible.

Cognitive behavioral therapy changes functional connectivity between medial prefrontal and anterior cingulate cortices.

PubMed

Yoshimura, Shinpei; Okamoto, Yasumasa; Matsunaga, Miki; Onoda, Keiichi; Okada, Go; Kunisato, Yoshihiko; Yoshino, Atsuo; Ueda, Kazutaka; Suzuki, Shin-Ichi; Yamawaki, Shigeto

2017-01-15

Depression is characterized by negative self-cognition. Our previous study (Yoshimura et al. 2014) revealed changes in brain activity after cognitive behavioral therapy (CBT) for depression, but changes in functional connectivity were not assessed. This study included 29 depressive patients and 15 healthy control participants. Functional Magnetic Resonance Imaging was used to investigate possible CBT-related functional connectivity changes associated with negative emotional self-referential processing. Depressed and healthy participants (overlapping with our previous study, Yoshimura et al. 2014) were included. We defined a seed region (medial prefrontal cortex) and coupled region (ACC) based on our previous study, and we examined changes in MPFC-ACC functional connectivity from pretreatment to posttreatment. CBT was associated with reduced functional connectivity between the MPFC and ACC. Symptom change with CBT was positively correlated with change in MPFC-ACC functional connectivity. Patients received pharmacotherapy including antidepressant. The present sample size was quite small and more study is needed. Statistical threshold in fMRI analysis was relatively liberal. CBT for depression may disrupt MPFC-ACC connectivity, with associated improvements in depressive symptoms and dysfunctional cognition. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptive noise reduction circuit for a sound reproduction system

NASA Technical Reports Server (NTRS)

Engebretson, A. Maynard (Inventor); O'Connell, Michael P. (Inventor)

1995-01-01

A noise reduction circuit for a hearing aid having an adaptive filter for producing a signal which estimates the noise components present in an input signal. The circuit includes a second filter for receiving the noise-estimating signal and modifying it as a function of a user's preference or as a function of an expected noise environment. The circuit also includes a gain control for adjusting the magnitude of the modified noise-estimating signal, thereby allowing for the adjustment of the magnitude of the circuit response. The circuit also includes a signal combiner for combining the input signal with the adjusted noise-estimating signal to produce a noise reduced output signal.

Resting-state fMRI in sleeping infants more closely resembles adult sleep than adult wakefulness

PubMed Central

Snyder, Abraham Z.; Tagliazucchi, Enzo; Laufs, Helmut; Elison, Jed; Emerson, Robert W.; Shen, Mark D.; Wolff, Jason J.; Botteron, Kelly N.; Dager, Stephen; Estes, Annette M.; Evans, Alan; Gerig, Guido; Hazlett, Heather C.; Paterson, Sarah J.; Schultz, Robert T.; Styner, Martin A.; Zwaigenbaum, Lonnie; Schlaggar, Bradley L.

2017-01-01

Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI. PMID:29149191

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.

PubMed

Georgiou-Karistianis, N; Akhlaghi, H; Corben, L A; Delatycki, M B; Storey, E; Bradshaw, J L; Egan, G F

2012-08-01

The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle prefrontal cortices, insulae, superior and inferior parietal lobules (LPs, LPi), occipital cortex and cerebellum, there was reduced functional activation across a range of brain regions (cortical, subcortical and cerebellar) in individuals with FRDA. The greater Simon effect behaviourally in individuals with FRDA, compared with controls, together with concomitant reductions in functional brain activation and reduced functional connectivity between cortical and sub-cortical regions, implies a likely disruption of cortico-cerebellar loops and ineffective engagement of cognitive/attention regions required for response suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

Resting-state fMRI in sleeping infants more closely resembles adult sleep than adult wakefulness.

PubMed

Mitra, Anish; Snyder, Abraham Z; Tagliazucchi, Enzo; Laufs, Helmut; Elison, Jed; Emerson, Robert W; Shen, Mark D; Wolff, Jason J; Botteron, Kelly N; Dager, Stephen; Estes, Annette M; Evans, Alan; Gerig, Guido; Hazlett, Heather C; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Zwaigenbaum, Lonnie; Schlaggar, Bradley L; Piven, Joseph; Pruett, John R; Raichle, Marcus

2017-01-01

Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI.

Choline partially prevents the impact of ethanol on the lipid raft dependent functions of l1 cell adhesion molecule.

PubMed

Tang, Ningfeng; Bamford, Penny; Jones, Jace; He, Min; Kane, Maureen A; Mooney, Sandra M; Bearer, Cynthia F

2014-11-01

Fetal alcohol spectrum disorder, the leading known cause of mental retardation, is caused by alcohol exposure during pregnancy. One mechanism of ethanol (EtOH) teratogenicity is the disruption of the functions of L1 cell adhesion molecule (L1). These functions include enhancement of neurite outgrowth, trafficking through lipid rafts, and signal transduction. Recent data have shown that choline supplementation of rat pups reduces the effects of EtOH on neurobehavior. We sought to determine whether choline could prevent the effect of EtOH on L1 function using a simple experimental system. Cerebellar granule neurons (CGN) from postnatal day 6 rat pups were cultured with and without supplemental choline, and the effects on L1 signaling, lipid raft distribution, and neurite outgrowth were measured in the presence or absence of EtOH. Choline significantly reduced the effect of EtOH on L1 signaling, the distribution of L1 in lipid rafts and L1-mediated neurite outgrowth. However, choline supplemented EtOH-exposed cultures remained significantly different than controls. Choline pretreatment of CGN significantly reduces the disruption of L1 function by EtOH, but does not completely return L1 function to baseline. This experimental system will enable discovery of the mechanism of the neuroprotective effect of choline. Copyright © 2014 by the Research Society on Alcoholism.

Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling.

PubMed

Mishina, Yuji; Starbuck, Michael W; Gentile, Michael A; Fukuda, Tomokazu; Kasparcova, Viera; Seedor, J Gregory; Hanks, Mark C; Amling, Michael; Pinero, Gerald J; Harada, Shun-ichi; Behringer, Richard R

2004-06-25

Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA (a type IA receptor for BMP) in osteoblasts for bone remodeling.

Reduced mandibular range of motion in Duchenne Muscular Dystrophy: predictive factors.

PubMed

van Bruggen, H W; Van Den Engel-Hoek, L; Steenks, M H; Bronkhorst, E M; Creugers, N H J; de Groot, I J M; Kalaykova, S I

2015-06-01

Patients with Duchenne muscular dystrophy (DMD) experience negative effects upon feeding and oral health. We aimed to determine whether the mandibular range of motion in DMD is impaired and to explore predictive factors for the active maximum mouth opening (aMMO). 23 patients with DMD (mean age 16.7 ± 7.7 years) and 23 controls were assessed using a questionnaire about mandibular function and impairments. All participants underwent a clinical examination of the masticatory system, including measurement of mandibular range of motion and variables related to mandibular movements. In all patients, quantitative ultrasound of the digastric muscle and the geniohyoid muscle and the motor function measure (MFM) scale were performed. The patients were divided into early and late ambulatory stage (AS), early non-ambulatory stage (ENAS) and late non-ambulatory stage (LNAS). All mandibular movements were reduced in the patient group (P < 0.001) compared to the controls. Reduction in the aMMO (<40 mm) was found in 26% of the total patient group. LNAS patients had significantly smaller mandibular movements compared to AS and ENAS (P < 0.05). Multiple linear regression analysis for aMMO revealed a positive correlation with the body height and disease progression, with MFM total score as the strongest independent risk factor (R(2) = 0.71). Mandibular movements in DMD are significantly reduced and become more hampered with loss of motor function, including the sitting position, arm function, and neck and head control. We suggest that measurement of the aMMO becomes a part of routine care of patients with DMD. © 2015 John Wiley & Sons Ltd.

Physiological and Functional Alterations after Spaceflight and Bed Rest.

PubMed

Mulavara, Ajitkumar P; Peters, Brian T; Miller, Chris A; Kofman, Igor S; Reschke, Millard F; Taylor, Laura C; Lawrence, Emily L; Wood, Scott J; Laurie, Steven S; Lee, Stuart M C; Buxton, Roxanne E; May-Phillips, Tiffany R; Stenger, Michael B; Ploutz-Snyder, Lori L; Ryder, Jeffrey W; Feiveson, Alan H; Bloomberg, Jacob J

2018-04-03

Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits. A test battery comprised of 7 functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 days of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included Control and Exercise groups to examine the effects of exercise during bed rest. Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased heart rate to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function, however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects. Bed rest data indicates that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the Exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular function, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance.

Preparation of transition metal nanoparticles and surfaces modified with (CO)polymers synthesized by RAFT

DOEpatents

McCormick, III., Charles L.; Lowe, Andrew B.; Sumerlin, Brent S.

2006-11-21

A new, facile, general one-phase method of generating thio-functionalized transition metal nanoparticles and surfaces modified by (co)polymers synthesized by the RAFT method is described. The method includes the stops of forming a (co)polymer in aqueous solution using the RAFT methodology, forming a colloidal transition metal precursor solution from an appropriate transition metal; adding the metal precursor solution or surface to the (co)polymer solution, adding a reducing agent into the solution to reduce the metal colloid in situ to produce the stabilized nanoparticles or surface, and isolating the stabilized nanoparticles or surface in a manner such that aggregation is minimized. The functionalized surfaces generated using these methods can further undergo planar surface modifications, such as functionalization with a variety of different chemical groups, expanding their utility and application.

Preparation of transition metal nanoparticles and surfaces modified with (co)polymers synthesized by RAFT

DOEpatents

McCormick, III, Charles L.; Lowe, Andrew B [Hattiesburg, MS; Sumerlin, Brent S [Pittsburgh, PA

2011-12-27

A new, facile, general one-phase method of generating thiol-functionalized transition metal nanoparticles and surfaces modified by (co)polymers synthesized by the RAFT method is described. The method includes the steps of forming a (co)polymer in aqueous solution using the RAFT methodology, forming a colloidal transition metal precursor solution from an appropriate transition metal; adding the metal precursor solution or surface to the (co)polymer solution, adding a reducing agent into the solution to reduce the metal colloid in situ to produce the stabilized nanoparticles or surface, and isolating the stabilized nanoparticles or surface in a manner such that aggregation is minimized. The functionalized surfaces generated using these methods can further undergo planar surface modifications, such as functionalization with a variety of different chemical groups, expanding their utility and application.

Epidural anaesthesia and analgesia - effects on surgical stress responses and implications for postoperative nutrition.

PubMed

Holte, K; Kehlet, H

2002-06-01

Surgical injury leads to an endocrine-metabolic and inflammatory response with protein catabolism, increased cardiovascular demands, impaired pulmonary function and paralytic ileus, the most important release mechanisms being afferent neural stimuli and inflammatory mediators. Epidural local anaesthetic blockade of afferent stimuli reduces endocrine metabolic responses, and improve postoperative catabolism. Furthermore, dynamic pain relief is achieved with improved pulmonary function and a pronounced reduction of postoperative ileus, thereby providing optimal conditions for improved mobilization and oral nutrition, and preservation of body composition and muscle function. Studies integrating continuous epidural local anaesthetics with enforced early nutrition and mobilization uniformly suggest an improved recovery, decreased hospital stay and convalescence. Epidural local anaesthetics should be included in a multi-modal rehabilitation programme after major surgical procedures in order to facilitate oral nutrition, improve recovery and reduce morbidity.

The influence of surface roughness on the contact stiffness and the contact filter effect in nonlinear wheel-track interaction

NASA Astrophysics Data System (ADS)

Lundberg, Oskar E.; Nordborg, Anders; Lopez Arteaga, Ines

2016-03-01

A state-dependent contact model including nonlinear contact stiffness and nonlinear contact filtering is used to calculate contact forces and rail vibrations with a time-domain wheel-track interaction model. In the proposed method, the full three-dimensional contact geometry is reduced to a point contact in order to lower the computational cost and to reduce the amount of required input roughness-data. Green's functions including the linear dynamics of the wheel and the track are coupled with a point contact model, leading to a numerically efficient model for the wheel-track interaction. Nonlinear effects due to the shape and roughness of the wheel and the rail surfaces are included in the point contact model by pre-calculation of functions for the contact stiffness and contact filters. Numerical results are compared to field measurements of rail vibrations for passenger trains running at 200 kph on a ballast track. Moreover, the influence of vehicle pre-load and different degrees of roughness excitation on the resulting wheel-track interaction is studied by means of numerical predictions.

Very High-Frequency (VHF) ionospheric scintillation fading measurements at Lima, Peru

NASA Technical Reports Server (NTRS)

Blank, H. A.; Golden, T. S.

1972-01-01

During the spring equinox of 1970, scintillating signals at VHF (136.4 MHz) were observed at Lima, Peru. The transmission originated from ATS 3 and was observed through a pair of antennas spaced 1200 feet apart on an east-west baseline. The empirical data were digitized, reduced, and analyzed. The results include amplitude probability density and distribution functions, time autocorrelation functions, cross correlation functions for the spaced antennas, and appropriate spectral density functions. Results show estimates of the statistics of the ground diffraction pattern to gain insight into gross ionospheric irregularity size, and irregularity velocity in the antenna planes.

Effectiveness of Acupuncture for Early Recovery of Bowel Function in Cancer: A Systematic Review and Meta-Analysis.

PubMed

Liu, Yi-Hua; Dong, Guang-Tong; Ye, Yang; Zheng, Jia-Bin; Zhang, Ying; Lin, Hong-Sheng; Wang, Xue-Qian

2017-01-01

The aim of this study was to evaluate the effects of acupuncture therapy to reduce the duration of postoperative ileus (POI) and to enhance bowel function in cancer patients. A systematic search of electronic databases for studies published from inception until January 2017 was carried out from six databases. Randomized controlled trials (RCTs) involving the use of acupuncture and acupressure for POI and bowel function in cancer patients were identified. Outcomes were extracted from each study and pooled to determine the risk ratio and standardized mean difference. 10 RCTs involving 776 cancer patients were included. Compared with control groups (no acupuncture, sham acupuncture, and other active therapies), acupuncture was associated with shorter time to first flatus and time to first defecation. A subgroup analysis revealed that manual acupuncture was more effective on the time to first flatus and the time to first defecation; electroacupuncture was better in reducing the length of hospital stay. Compared with control groups (sham or no acupressure), acupressure was associated with shorter time to first flatus. However, GRADE approach indicated a low quality of evidence. Acupuncture and acupressure showed large effect size with significantly poor or inferior quality of included trials for enhancing bowel function in cancer patients after surgery. Further well-powered evidence is needed.

Brain connectivity aberrations in anabolic-androgenic steroid users.

PubMed

Westlye, Lars T; Kaufmann, Tobias; Alnæs, Dag; Hullstein, Ingunn R; Bjørnebekk, Astrid

2017-01-01

Sustained anabolic-androgenic steroid (AAS) use has adverse behavioral consequences, including aggression, violence and impulsivity. Candidate mechanisms include disruptions of brain networks with high concentrations of androgen receptors and critically involved in emotional and cognitive regulation. Here, we tested the effects of AAS on resting-state functional brain connectivity in the largest sample of AAS-users to date. We collected resting-state functional magnetic resonance imaging (fMRI) data from 151 males engaged in heavy resistance strength training. 50 users tested positive for AAS based on the testosterone to epitestosterone (T/E) ratio and doping substances in urine. 16 previous users and 59 controls tested negative. We estimated brain network nodes and their time-series using ICA and dual regression and defined connectivity matrices as the between-node partial correlations. In line with the emotional and behavioral consequences of AAS, current users exhibited reduced functional connectivity between key nodes involved in emotional and cognitive regulation, in particular reduced connectivity between the amygdala and default-mode network (DMN) and between the dorsal attention network (DAN) and a frontal node encompassing the superior and inferior frontal gyri (SFG/IFG) and the anterior cingulate cortex (ACC), with further reductions as a function of dependency, lifetime exposure, and cycle state (on/off).

Research on Near Roadway and Other Near Source Air Pollution

EPA Pesticide Factsheets

Research has shown that living and working near sources of air pollution can lead to higher exposures to air contaminants many of which contribute to adverse health effects including reduced lung function, asthma, cardiovascular disease and premature death

Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats

EPA Science Inventory

Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To addre...

A Triple-Mode Flexible E-Skin Sensor Interface for Multi-Purpose Wearable Applications

PubMed Central

Kim, Sung-Woo; Lee, Youngoh; Park, Jonghwa; Kim, Seungmok; Chae, Heeyoung; Ko, Hyunhyub

2017-01-01

This study presents a flexible wireless electronic skin (e-skin) sensor system that includes a multi-functional sensor device, a triple-mode reconfigurable readout integrated circuit (ROIC), and a mobile monitoring interface. The e-skin device’s multi-functionality is achieved by an interlocked micro-dome array structure that uses a polyvinylidene fluoride and reduced graphene oxide (PVDF/RGO) composite material that is inspired by the structure and functions of the human fingertip. For multi-functional implementation, the proposed triple-mode ROIC is reconfigured to support piezoelectric, piezoresistance, and pyroelectric interfaces through single-type e-skin sensor devices. A flexible system prototype was developed and experimentally verified to provide various wireless wearable sensing functions—including pulse wave, voice, chewing/swallowing, breathing, knee movements, and temperature—while their real-time sensed data are displayed on a smartphone. PMID:29286312

The effects of reduced dopamine transporter function and chronic lithium on motivation, probabilistic learning, and neurochemistry in mice: Modeling bipolar mania.

PubMed

Milienne-Petiot, Morgane; Kesby, James P; Graves, Mary; van Enkhuizen, Jordy; Semenova, Svetlana; Minassian, Arpi; Markou, Athina; Geyer, Mark A; Young, Jared W

2017-02-01

Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses. The effects of reducing dopamine transporter (DAT) functioning via genetic (knockdown vs. wild-type littermates), or pharmacological (GBR12909- vs. vehicle-treated C57BL/6J mice) means were assessed in the probabilistic reversal learning task (PRLT), and progressive ratio breakpoint (PRB) test, during either water or chronic lithium treatment. These tasks quantify reward learning and effortful motivation, respectively. Neurochemistry was performed on brain samples of DAT mutants ± chronic lithium using high performance liquid chromatography. Reduced DAT functioning increased reversals in the PRLT, an effect partially attenuated by chronic lithium. Chronic lithium alone slowed PRLT acquisition. Reduced DAT functioning increased motivation (PRB), an effect attenuated by lithium in GBR12909-treated mice. Neurochemical analyses revealed that DAT knockdown mice exhibited elevated homovanillic acid levels, but that lithium had no effect on these elevated levels. Reducing DAT functioning recreates many aspects of BD mania including hypermotivation and improved reversal learning (switching), as well as elevated homovanillic acid levels. Chronic lithium only exerted main effects, impairing learning and elevating norepinephrine and serotonin levels of mice, not specifically treating the underlying mechanisms identified in these models. Copyright © 2016 Elsevier Ltd. All rights reserved.

[An Occupational Therapy Intervention for People With Dementia].

PubMed

Ke, Hung-Hsun

2018-02-01

The percentage of individuals with dementia worldwide is increasing with the continued trend toward global trend overall. As options for the medical treatment of dementia remain limited, combined, non-pharmacological interventions are necessary to maintain and slow the degeneration of functional capabilities. Additionally, there is a need to help caregivers develop better patterns of care and methods to reduce the burden of care. Therefore, occupational therapists play an important role in the dementia care team. This article introduces how occupational therapists help dementia patient maintain their functional capabilities and delay degeneration and help caregivers reduce their burden of care. Both activities are based on the concept of occupational therapy, which includes three important components: people, activities, and the environment.

EXTENDING THE FLOOR AND THE CEILING FOR ASSESSMENT OF PHYSICAL FUNCTION

PubMed Central

Fries, James F.; Lingala, Bharathi; Siemons, Liseth; Glas, Cees A. W.; Cella, David; Hussain, Yusra N; Bruce, Bonnie; Krishnan, Eswar

2014-01-01

Objective The objective of the current study was to improve the assessment of physical function by improving the precision of assessment at the floor (extremely poor function) and at the ceiling (extremely good health) of the health continuum. Methods Under the NIH PROMIS program, we developed new physical function floor and ceiling items to supplement the existing item bank. Using item response theory (IRT) and the standard PROMIS methodology, we developed 30 floor items and 26 ceiling items and administered them during a 12-month prospective observational study of 737 individuals at the extremes of health status. Change over time was compared across anchor instruments and across items by means of effect sizes. Using the observed changes in scores, we back-calculated sample size requirements for the new and comparison measures. Results We studied 444 subjects with chronic illness and/or extreme age, and 293 generally fit subjects including athletes in training. IRT analyses confirmed that the new floor and ceiling items outperformed reference items (p<0.001). The estimated post-hoc sample size requirements were reduced by a factor of two to four at the floor and a factor of two at the ceiling. Conclusion Extending the range of physical function measurement can substantially improve measurement quality, can reduce sample size requirements and improve research efficiency. The paradigm shift from Disability to Physical Function includes the entire spectrum of physical function, signals improvement in the conceptual base of outcome assessment, and may be transformative as medical goals more closely approach societal goals for health. PMID:24782194

Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective.

PubMed

Krystal, John H; Anticevic, Alan; Yang, Genevieve J; Dragoi, George; Driesen, Naomi R; Wang, Xiao-Jing; Murray, John D

2017-05-15

The functional optimization of neural ensembles is central to human higher cognitive functions. When the functions through which neural activity is tuned fail to develop or break down, symptoms and cognitive impairments arise. This review considers ways in which disturbances in the balance of excitation and inhibition might develop and be expressed in cortical networks in association with schizophrenia. This presentation is framed within a developmental perspective that begins with disturbances in glutamate synaptic development in utero. It considers developmental correlates and consequences, including compensatory mechanisms that increase intrinsic excitability or reduce inhibitory tone. It also considers the possibility that these homeostatic increases in excitability have potential negative functional and structural consequences. These negative functional consequences of disinhibition may include reduced working memory-related cortical activity associated with the downslope of the "inverted-U" input-output curve, impaired spatial tuning of neural activity and impaired sparse coding of information, and deficits in the temporal tuning of neural activity and its implication for neural codes. The review concludes by considering the functional significance of noisy activity for neural network function. The presentation draws on computational neuroscience and pharmacologic and genetic studies in animals and humans, particularly those involving N-methyl-D-aspartate glutamate receptor antagonists, to illustrate principles of network regulation that give rise to features of neural dysfunction associated with schizophrenia. While this presentation focuses on schizophrenia, the general principles outlined in the review may have broad implications for considering disturbances in the regulation of neural ensembles in psychiatric disorders. Published by Elsevier Inc.

Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study.

PubMed

Bartlett, David B; Willis, Leslie H; Slentz, Cris A; Hoselton, Andrew; Kelly, Leslie; Huebner, Janet L; Kraus, Virginia B; Moss, Jennifer; Muehlbauer, Michael J; Spielmann, Guillaume; Kraus, William E; Lord, Janet M; Huffman, Kim M

2018-06-14

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which adults have significant joint issues leading to poor health. Poor health is compounded by many factors, including exercise avoidance and increased risk of opportunistic infection. Exercise training can improve the health of patients with RA and potentially improve immune function; however, information on the effects of high-intensity interval training (HIIT) in RA is limited. We sought to determine whether 10 weeks of a walking-based HIIT program would be associated with health improvements as measured by disease activity and aerobic fitness. Further, we assessed whether HIIT was associated with improved immune function, specifically antimicrobial/bacterial functions of neutrophils and monocytes. Twelve physically inactive adults aged 64 ± 7 years with either seropositive or radiographically proven (bone erosions) RA completed 10 weeks of high-intensity interval walking. Training consisted of 3 × 30-minute sessions/week of ten ≥ 60-second intervals of high intensity (80-90% VO 2reserve ) separated by similar bouts of lower-intensity intervals (50-60% VO 2reserve ). Pre- and postintervention assessments included aerobic and physical function; disease activity as measured by Disease Activity score in 28 joints (DAS28), self-perceived health, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR); plasma interleukin (IL)-1β, IL-6, chemokine (C-X-C motif) ligand (CXCL)-8, IL-10, and tumor necrosis factor (TNF)-α concentrations; and neutrophil and monocyte phenotypes and functions. Despite minimal body composition change, cardiorespiratory fitness increased by 9% (change in both relative and absolute aerobic capacity; p < 0.001), and resting blood pressure and heart rate were both reduced (both p < 0.05). Postintervention disease activity was reduced by 38% (DAS28; p = 0.001) with significant reductions in ESR and swollen joints as well as improved self-perceived health. Neutrophil migration toward CXCL-8 (p = 0.003), phagocytosis of Escherichia coli (p = 0.03), and ROS production (p < 0.001) all increased following training. The frequency of cluster of differentiation 14-positive (CD14 + )/CD16 + monocytes was reduced (p = 0.002), with both nonclassical (CD14 dim /CD16 bright ) and intermediate (CD14 bright /CD16 positive ) monocytes being reduced (both p < 0.05). Following training, the cell surface expression of intermediate monocyte Toll-like receptor 2 (TLR2), TLR4, and HLA-DR was reduced (all p < 0.05), and monocyte phagocytosis of E. coli increased (p = 0.02). No changes were observed for inflammatory markers IL-1β, IL-6, CXCL-8, IL-10, CRP, or TNF-α. We report for the first time, to our knowledge, that a high-intensity interval walking protocol in older adults with stable RA is associated with reduced disease activity, improved cardiovascular fitness, and improved innate immune functions, indicative of reduced infection risk and inflammatory potential. Importantly, the exercise program was well tolerated by these patients. ClinicalTrials.gov, NCT02528344 . Registered on 19 August 2015.

CHERISH (collaboration for hospitalised elders reducing the impact of stays in hospital): protocol for a multi-site improvement program to reduce geriatric syndromes in older inpatients.

PubMed

Mudge, Alison M; Banks, Merrilyn D; Barnett, Adrian G; Blackberry, Irene; Graves, Nicholas; Green, Theresa; Harvey, Gillian; Hubbard, Ruth E; Inouye, Sharon K; Kurrle, Sue; Lim, Kwang; McRae, Prue; Peel, Nancye M; Suna, Jessica; Young, Adrienne M

2017-01-09

Older inpatients are at risk of hospital-associated geriatric syndromes including delirium, functional decline, incontinence, falls and pressure injuries. These contribute to longer hospital stays, loss of independence, and death. Effective interventions to reduce geriatric syndromes remain poorly implemented due to their complexity, and require an organised approach to change care practices and systems. Eat Walk Engage is a complex multi-component intervention with structured implementation, which has shown reduced geriatric syndromes and length of stay in pilot studies at one hospital. This study will test effectiveness of implementing Eat Walk Engage using a multi-site cluster randomised trial to inform transferability of this intervention. A hybrid study design will evaluate the effectiveness and implementation strategy of Eat Walk Engage in a real-world setting. A multisite cluster randomised study will be conducted in 8 medical and surgical wards in 4 hospitals, with one ward in each site randomised to implement Eat Walk Engage (intervention) and one to continue usual care (control). Intervention wards will be supported to develop and implement locally tailored strategies to enhance early mobility, nutrition, and meaningful activities. Resources will include a trained, mentored facilitator, audit support, a trained healthcare assistant, and support by an expert facilitator team using the i-PARIHS implementation framework. Patient outcomes and process measures before and after intervention will be compared between intervention and control wards. Primary outcomes are any hospital-associated geriatric syndrome (delirium, functional decline, falls, pressure injuries, new incontinence) and length of stay. Secondary outcomes include discharge destination; 30-day mortality, function and quality of life; 6 month readmissions; and cost-effectiveness. Process measures including patient interviews, activity mapping and mealtime audits will inform interventions in each site and measure improvement progress. Factors influencing the trajectory of implementation success will be monitored on implementation wards. Using a hybrid design and guided by an explicit implementation framework, the CHERISH study will establish the effectiveness, cost-effectiveness and transferability of a successful pilot program for improving care of older inpatients, and identify features that support successful implementation. ACTRN12615000879561 registered prospectively 21/8/2015.

Fast computation of the electrolyte-concentration transfer function of a lithium-ion cell model

NASA Astrophysics Data System (ADS)

Rodríguez, Albert; Plett, Gregory L.; Trimboli, M. Scott

2017-08-01

One approach to creating physics-based reduced-order models (ROMs) of battery-cell dynamics requires first generating linearized Laplace-domain transfer functions of all cell internal electrochemical variables of interest. Then, the resulting infinite-dimensional transfer functions can be reduced by various means in order to find an approximate low-dimensional model. These methods include Padé approximation or the Discrete-Time Realization algorithm. In a previous article, Lee and colleagues developed a transfer function of the electrolyte concentration for a porous-electrode pseudo-two-dimensional lithium-ion cell model. Their approach used separation of variables and Sturm-Liouville theory to compute an infinite-series solution to the transfer function, which they then truncated to a finite number of terms for reasons of practicality. Here, we instead use a variation-of-parameters approach to arrive at a different representation of the identical solution that does not require a series expansion. The primary benefits of the new approach are speed of computation of the transfer function and the removal of the requirement to approximate the transfer function by truncating the number of terms evaluated. Results show that the speedup of the new method can be more than 3800.

Moderating effect of intrinsic religiosity on the relationship between depression and cognitive function among community-dwelling older adults.

PubMed

Foong, Hui Foh; Hamid, Tengku Aizan; Ibrahim, Rahimah; Haron, Sharifah Azizah

2018-04-01

Research has found that depression in later life is associated with cognitive impairment. Thus, the mechanism to reduce the effect of depression on cognitive function is warranted. In this paper, we intend to examine whether intrinsic religiosity mediates the association between depression and cognitive function. The study included 2322 nationally representative community-dwelling elderly in Malaysia, randomly selected through a multi-stage proportional cluster random sampling from Peninsular Malaysia. The elderly were surveyed on socio-demographic information, cognitive function, depression and intrinsic religiosity. A four-step moderated hierarchical regression analysis was employed to test the moderating effect. Statistical analyses were performed using SPSS (version 15.0). Bivariate analyses showed that both depression and intrinsic religiosity had significant relationships with cognitive function. In addition, four-step moderated hierarchical regression analysis revealed that the intrinsic religiosity moderated the association between depression and cognitive function, after controlling for selected socio-demographic characteristics. Intrinsic religiosity might reduce the negative effect of depression on cognitive function. Professionals who are working with depressed older adults should seek ways to improve their intrinsic religiosity as one of the strategies to prevent cognitive impairment.

Method of producing catalytic material for fabricating nanostructures

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

Seals, Roland D.; Menchhofer, Paul A.; Howe, Jane Y.

Methods of fabricating nano-catalysts are described. In some embodiments the nano-catalyst is formed from a powder-based substrate material and is some embodiments the nano-catalyst is formed from a solid-based substrate material. In some embodiments the substrate material may include metal, ceramic, or silicon or another metalloid. The nano-catalysts typically have metal nanoparticles disposed adjacent the surface of the substrate material. The methods typically include functionalizing the surface of the substrate material with a chelating agent, such as a chemical having dissociated carboxyl functional groups (--COO), that provides an enhanced affinity for metal ions. The functionalized substrate surface may then bemore » exposed to a chemical solution that contains metal ions. The metal ions are then bound to the substrate material and may then be reduced, such as by a stream of gas that includes hydrogen, to form metal nanoparticles adjacent the surface of the substrate.« less

Method of producing catalytic materials for fabricating nanostructures

DOEpatents

Seals, Roland D; Menchhofer, Paul A; Howe, Jane Y; Wang, Wei

2013-02-19

Methods of fabricating nano-catalysts are described. In some embodiments the nano-catalyst is formed from a powder-based substrate material and is some embodiments the nano-catalyst is formed from a solid-based substrate material. In some embodiments the substrate material may include metal, ceramic, or silicon or another metalloid. The nano-catalysts typically have metal nanoparticles disposed adjacent the surface of the substrate material. The methods typically include functionalizing the surface of the substrate material with a chelating agent, such as a chemical having dissociated carboxyl functional groups (--COO), that provides an enhanced affinity for metal ions. The functionalized substrate surface may then be exposed to a chemical solution that contains metal ions. The metal ions are then bound to the substrate material and may then be reduced, such as by a stream of gas that includes hydrogen, to form metal nanoparticles adjacent the surface of the substrate.

Usability Testing of the BRANCH Smartphone App Designed to Reduce Harmful Drinking in Young Adults

PubMed Central

Deluca, Paolo; Drummond, Colin; Watson, Rod; Dunne, Jacklyn; Kimergård, Andreas

2017-01-01

Background Electronic screening and brief intervention (eSBI) apps demonstrate potential to reduce harmful drinking. However, low user engagement rates with eSBI reduce overall effectiveness of interventions. As “Digital Natives,” young adults have high expectations of app quality. Ensuring that the design, content, and functionality of an eSBI app are acceptable to young adults is an integral stage to the development process. Objective The objective of this study was to identify usability barriers and enablers for an app, BRANCH, targeting harmful drinking in young adults. Methods The BRANCH app contains a drinking diary, alcohol reduction goal setting functions, normative drinking feedback, and information on risks and advice for cutting down. The app includes a social feature personalized to motivate cutting down and to promote engagement with a point-based system for usage. Three focus groups were conducted with 20 users who had tested the app for 1 week. A detailed thematic analysis was undertaken. Results The first theme, “Functionality” referred to how users wanted an easy-to-use interface, with minimum required user-input. Poor functionality was considered a major usability barrier. The second theme, “Design” described how an aesthetic with minimum text, clearly distinguishable tabs and buttons and appealing infographics was integral to the level of usability. The final theme, “Content” described how participants wanted all aspects of the app to be automatically personalized to them, as well as providing them with opportunities to personalize the app themselves, with increased options for social connectivity. Conclusions There are high demands for apps such as BRANCH that target skilled technology users including young adults. Key areas to optimize eSBI app development that emerged from testing BRANCH with representative users include high-quality functionality, appealing aesthetics, and improved personalization. PMID:28790022

Structural and Functional Integrity of the Intraparietal Sulcus in Moderate and Severe Traumatic Brain Injury

PubMed Central

Sours, Chandler; Raghavan, Prashant; Medina, Alexandre E.; Roys, Steven; Jiang, Li; Zhuo, Jiachen

2017-01-01

Abstract Severe and moderate traumatic brain injury (sTBI) often results in long-term cognitive deficits such as reduced processing speed and attention. The intraparietal sulcus (IPS) is a neocortical structure that plays a crucial role in the deeply interrelated processes of multi-sensory processing and top down attention. Therefore, we hypothesized that disruptions in the functional and structural connections of the IPS may play a role in the development of such deficits. To examine these connections, we used resting state magnetic resonance imaging (rsfMRI and diffusion kurtosis imaging (DKI) in a cohort of 27 patients with sTBI (29.3 ± 8.9 years) and 27 control participants (29.8 ± 10.3 years). Participants were prospectively recruited and received rsfMRI and neuropsychological assessments including the Automated Neuropsychological Assessment Metrics (ANAM) at greater than 6 months post-injury. A subset of participants received a DKI scan. Results suggest that patients with sTBI performed worse than control participants on multiple subtests of the ANAM suggesting reduced cognitive performance. Reduced resting state functional connectivity between the IPS and cortical regions associated with multi-sensory processing and the dorsal attention network was observed in the patients with sTBI. The patients also showed reduced structural integrity of the superior longitudinal fasciculus (SLF), a key white matter tract connecting the IPS to anterior frontal areas, as measured by reduced mean kurtosis (MK) and fractional anisotropy (FA) and increased mean diffusivity (MD). Further, this reduced structural integrity of the SLF was associated with a reduction in overall cognitive performance. These findings suggest that disruptions in the structural and functional connectivity of the IPS may contribute to chronic cognitive deficits experienced by these patients. PMID:27931179

Structural and Functional Integrity of the Intraparietal Sulcus in Moderate and Severe Traumatic Brain Injury.

PubMed

Sours, Chandler; Raghavan, Prashant; Medina, Alexandre E; Roys, Steven; Jiang, Li; Zhuo, Jiachen; Gullapalli, Rao P

2017-04-01

Severe and moderate traumatic brain injury (sTBI) often results in long-term cognitive deficits such as reduced processing speed and attention. The intraparietal sulcus (IPS) is a neocortical structure that plays a crucial role in the deeply interrelated processes of multi-sensory processing and top down attention. Therefore, we hypothesized that disruptions in the functional and structural connections of the IPS may play a role in the development of such deficits. To examine these connections, we used resting state magnetic resonance imaging (rsfMRI and diffusion kurtosis imaging (DKI) in a cohort of 27 patients with sTBI (29.3 ± 8.9 years) and 27 control participants (29.8 ± 10.3 years). Participants were prospectively recruited and received rsfMRI and neuropsychological assessments including the Automated Neuropsychological Assessment Metrics (ANAM) at greater than 6 months post-injury. A subset of participants received a DKI scan. Results suggest that patients with sTBI performed worse than control participants on multiple subtests of the ANAM suggesting reduced cognitive performance. Reduced resting state functional connectivity between the IPS and cortical regions associated with multi-sensory processing and the dorsal attention network was observed in the patients with sTBI. The patients also showed reduced structural integrity of the superior longitudinal fasciculus (SLF), a key white matter tract connecting the IPS to anterior frontal areas, as measured by reduced mean kurtosis (MK) and fractional anisotropy (FA) and increased mean diffusivity (MD). Further, this reduced structural integrity of the SLF was associated with a reduction in overall cognitive performance. These findings suggest that disruptions in the structural and functional connectivity of the IPS may contribute to chronic cognitive deficits experienced by these patients.

Relationship between Testicular Volume and Conventional or Nonconventional Sperm Parameters

PubMed Central

Condorelli, Rosita; Calogero, Aldo E.; La Vignera, Sandro

2013-01-01

Background. Reduced testicular volume (TV) (<12 cm3) is associated with lower testicular function. Several studies explored the conventional sperm parameters (concentration, motility, and morphology) and the endocrine function (gonadotropins and testosterone serum concentrations) in the patients with reduction of TV. No other parameters have been examined. Aim. This study aims at evaluating some biofunctional sperm parameters by flow cytometry in the semen of men with reduced TV compared with that of subjects with normal TV. Methods. 78 patients without primary scrotal disease were submitted to ultrasound evaluation of the testis. They were divided into two groups according to testicular volume: A Group, including 40 patients with normal testicular volume (TV > 15 cm3) and B Group, including 38 patients with reduced testicular volume (TV ≤ 12 cm3). All patients underwent serum hormone concentration, conventional and biofunctional (flow cytometry) sperm parameters evaluation. Results. With regard to biofunctional sperm parameters, all values (mitochondrial membrane potential, phosphatidylserine externalization, chromatin compactness, and DNA fragmentation) were strongly negatively correlated with testicular volume (P < 0.0001). Conclusions. This study for the first time in the literature states that the biofunctional sperm parameters worsen and with near linear correlation, with decreasing testicular volume. PMID:24089610

Powered wheel for aircraft

NASA Technical Reports Server (NTRS)

Long, M. J.; Irick, S. C.; Van Ausdal, R. K.

1977-01-01

Single integral unit includes motor, gearbox, and clutch. Device has two-speed capability, fits within aerodynamic contours of aircraft, operates with onboard power source, does not interfere with normal landing gear functions, reduces use of regular brakes in congested areas, and provides locomotion and supplementary braking capability.

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2014 CFR

2014-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

Adjustable Optical-Fiber Attenuator

NASA Technical Reports Server (NTRS)

Buzzetti, Mike F.

1994-01-01

Adjustable fiber-optic attenuator utilizes bending loss to reduce strength of light transmitted along it. Attenuator functions without introducing measurable back-reflection or insertion loss. Relatively insensitive to vibration and changes in temperature. Potential applications include cable television, telephone networks, other signal-distribution networks, and laboratory instrumentation.

Validation of Procedures for Monitoring Crewmember Immune Function

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

2009-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation, however the nature of the phenomenon as it equilibrates over longer flights has not been determined. This dysregulation may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk (if any) for exploration-class space flight is unknown, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. The objective of this Supplemental Medical Objective (SMO) is to determine the status of the immune system, physiological stress and latent viral reactivation (a clinical outcome that can be measured) during both short and long-duration spaceflight. In addition, this study will develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. Pre-mission, in-flight and post-flight blood and saliva samples will be obtained from participating crewmembers. Assays included peripheral immunophenotype, T cell function, cytokine profiles (RNA, intracellular, secreted), viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. This study is currently ongoing. To date, 10 short duration and 5 long-duration crewmembers have completed the study. Technically, the study is progressing well. In-flight blood samples are being collected, and returned for analysis, including functional assays that require live cells. For all in-flight samples to date, sample viability has been acceptable. Preliminary data (n = 4/7; long/short duration, respectively) indicate that distribution of most peripheral leukocyte subsets is largely unaltered during flight. Exceptions include elevated T cells, reduced B/NK cells, increased memory T cells and increased central memory CD8+ T cells. General T cell function, early blastogenesis response to mitogenic stimulation, is markedly reduced in-flight. In-vivo cytokine production profiles are altered, with in-flight dysregulation observed in the Th1/Th2/Treg equilibrium. EBV specific T cell levels are increased during flight, whereas their function is reduced. VZV reactivation was observed inflight and several days post flight with highest levels measured later during long-duration flight. The shedding of CMV in the urine was detected of 4/5 long duration and 4/7 short duration crewmembers. Plasma cortisol was not elevated during flight. Further data will be required to validate the initial observations.

Cardiac regulation in the socially monogamous prairie vole

PubMed Central

Grippo, Angela J.; Lamb, Damon G.; Carter, C. Sue; Porges, Stephen W.

2007-01-01

Social experiences, both positive and negative, may influence cardiovascular regulation. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form social bonds similar to those seen in primates, and this species may provide a useful model for investigating neural and social regulation of cardiac function. Cardiac regulation has not been studied previously in the prairie vole. Radiotelemetry transmitters were implanted into adult female prairie voles under anesthesia, and electrocardiographic parameters were recorded. Autonomic blockade was performed using atenolol (8 mg/kg ip) and atropine methyl nitrate (4 mg/kg ip). Several variables were evaluated, including heart rate (HR), HR variability and the amplitude of respiratory sinus arrhythmia. Sympathetic blockade significantly reduced HR. Parasympathetic blockade significantly increased HR, and reduced HR variability and the amplitude of respiratory sinus arrhythmia. Combined autonomic blockade significantly increased HR, and reduced HR variability and respiratory sinus arrhythmia amplitude. The data indicate that autonomic function in prairie voles shares similarities with primates, with a predominant vagal influence on cardiac regulation. The current results provide a foundation for studying neural and social regulation of cardiac function during different behavioral states in this socially monogamous rodent model. PMID:17107695

Correlation Immunity, Avalanche Features, and Other Cryptographic Properties of Generalized Boolean Functions

DTIC Science & Technology

2017-09-01

information is estimated to average 1 hour per response, including the time for reviewing instruction, searching existing data sources, gathering and...maintaining the data needed, and completing and reviewing the collection of information . Send comments regarding this burden estimate or any other aspect...of this collection of information , including suggestions for reducing this burden to Washington headquarters Services, Directorate for Information

Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly.

PubMed

Alehagen, Urban; Aaseth, Jan; Alexander, Jan; Johansson, Peter

2018-01-01

Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating. Clinicaltrials.gov NCT01443780.

Predicting cognitive function from clinical measures of physical function and health status in older adults.

PubMed

Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa

2015-01-01

Current research suggests that the neuropathology of dementia-including brain changes leading to memory impairment and cognitive decline-is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1-L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a clinical setting.

Enhancement of Functional Connectivity, Working Memory and Inhibitory Control on Multi-modal Brain MR Imaging with Rifaximin in Cirrhosis: Implications for the Gut-Liver-Brain Axis

PubMed Central

Ahluwalia, Vishwadeep; Wade, James B; Heuman, Douglas M; Hammeke, Thomas A; Sanyal, Arun J; Sterling, Richard K; Stravitz, R. Todd; Luketic, Velimir; Siddiqui, Mohammad S; Puri, Puneet; Fuchs, Michael; Lennon, Micheal J; Kraft, Kenneth A; Gilles, HoChong; White, Melanie B; Noble, Nicole A; Bajaj, Jasmohan S

2014-01-01

Objective Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. Aim To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p=0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. Conclusion A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE. PMID:24590688

Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: implications for the gut-liver-brain axis.

PubMed

Ahluwalia, Vishwadeep; Wade, James B; Heuman, Douglas M; Hammeke, Thomas A; Sanyal, Arun J; Sterling, Richard K; Stravitz, R Todd; Luketic, Velimir; Siddiqui, Mohammad S; Puri, Puneet; Fuchs, Michael; Lennon, Micheal J; Kraft, Kenneth A; Gilles, HoChong; White, Melanie B; Noble, Nicole A; Bajaj, Jasmohan S

2014-12-01

Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. RESULTS were compared before/after rifaximin. 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.

SSRI-reduced platelet reactivity in non-responding patients with life-long Recurrent Depressive Disorder: Detection and involved mechanisms.

PubMed

Aleksovski, Boris; Neceva, Violeta; Vujović, Viktorija; Manusheva, Nensi; Rendevski, Vladimir; Novotni, Antoni; Filipce, Ana; Spasovska, Anastazija; Sofijanova, Aspazija; Aleksovski, Vasko; Gjorgoski, Icko

2018-05-01

Adverse effects with bleeding disorders are often associated with the administration of SSRI in depression, although the exact mechanisms remain contradicting. This study is aimed at detecting and exploring the mechanisms of SSRI-induced changes in platelet reactivity in non-responding patients with Recurrent Depressive Disorder (RDD) and life-long exposure to antidepressants. Thirty-one patients and thirty-one healthy controls were included in the study. A comprehensive approach which includes evaluation of peripheral markers and microscopic analyses of platelet morphology changes has been used. RDD SSRI patients have shown blunted aggregatory responses towards collagen and epinephrine. Evident differences in the microscopic evaluation of platelet morphology were observed between the groups, with inherent absence of micro-aggregates and platelet shape changes within the patients; after quantification, the sensitivity and specificity of this method were assessed as high. The abnormalities were found in association with lower platelet serotonin content and high fluctuations of free plasma serotonin levels. Changes in the levels of CRP, fibrinogen and nitric oxide were not observed. Macroplatelets were also detected within RDD SSRI patients via increased MPV, PDW and P-LCR, which were associated with discoid shape and without procoagulant activity. The microscopic evaluation might be useful as a simple method for detection of SSRI-reduced platelet function for research purposes or systematic correlations with other biochemical parameters. The mechanisms involved in SSRI-reduced platelet function in non-responding RDD patients are complex, including combined effects of lower platelet serotonin content, high fluctuations in plasma serotonin concentration and abnormal α-AR function. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reverse genetic characterization of two paralogous acetoacetyl CoA thiolase genes in Arabidopsis reveals their importance in plant growth and development

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

Jin, Huanan; Song, Zhihong; Nikolau, Basil J.

Acetoacetyl CoA thiolase (AACT, EC 2.3.1.9) catalyzes the condensation of two acetyl CoA molecules to form acetoacetyl CoA. Two AACT‐encoding genes, At5g47720 (AACT1) and At5g48230 (AACT2), were functionally identified in the Arabidopsis genome by direct enzymological assays and functional expression in yeast. Promoter::GUS fusion experiments indicated that AACT1 is primarily expressed in the vascular system and AACT2 is highly expressed in root tips, young leaves, top stems and anthers. Characterization of T‐DNA insertion mutant alleles at each AACT locus established that AACT2 function is required for embryogenesis and for normal male gamete transmission. In contrast, plants lacking AACT1 function are completely viablemore » and show no apparent growth phenotypes, indicating that AACT1 is functionally redundant with respect to AACT2 function. RNAi lines that express reduced levels of AACT2 show pleiotropic phenotypes, including reduced apical dominance, elongated life span and flowering duration, sterility, dwarfing, reduced seed yield and shorter root length. Microscopic analysis reveals that the reduced stature is caused by a reduction in cell size and fewer cells, and male sterility is caused by loss of the pollen coat and premature degeneration of the tapetal cells. Biochemical analyses established that the roots of AACT2 RNAi plants show quantitative and qualitative alterations in phytosterol profiles. These phenotypes and biochemical alterations are reversed when AACT2 RNAi plants are grown in the presence of mevalonate, which is consistent with the role of AACT2 in generating the bulk of the acetoacetyl CoA precursor required for the cytosol‐localized, mevalonate‐derived isoprenoid biosynthetic pathway.« less

Identification of segregated regions in the functional brain connectome of autistic patients by a combination of fuzzy spectral clustering and entropy analysis

PubMed Central

Sato, João Ricardo; Balardin, Joana; Vidal, Maciel Calebe; Fujita, André

2016-01-01

Background Several neuroimaging studies support the model of abnormal development of brain connectivity in patients with autism-spectrum disorders (ASD). In this study, we aimed to test the hypothesis of reduced functional network segregation in autistic patients compared with controls. Methods Functional MRI data from children acquired under a resting-state protocol (Autism Brain Imaging Data Exchange [ABIDE]) were submitted to both fuzzy spectral clustering (FSC) with entropy analysis and graph modularity analysis. Results We included data from 814 children in our analysis. We identified 5 regions of interest comprising the motor, temporal and occipito-temporal cortices with increased entropy (p < 0.05) in the clustering structure (i.e., more segregation in the controls). Moreover, we noticed a statistically reduced modularity (p < 0.001) in the autistic patients compared with the controls. Significantly reduced eigenvector centrality values (p < 0.05) in the patients were observed in the same regions that were identified in the FSC analysis. Limitations There is considerable heterogeneity in the fMRI acquisition protocols among the sites that contributed to the ABIDE data set (e.g., scanner type, pulse sequence, duration of scan and resting-state protocol). Moreover, the sites differed in many variables related to sample characterization (e.g., age, IQ and ASD diagnostic criteria). Therefore, we cannot rule out the possibility that additional differences in functional network organization would be found in a more homogeneous data sample of individuals with ASD. Conclusion Our results suggest that the organization of the whole-brain functional network in patients with ASD is different from that observed in controls, which implies a reduced modularity of the brain functional networks involved in sensorimotor, social, affective and cognitive processing. PMID:26505141

Symptoms and health-related quality of life in patients with advanced cancer - A population-based study in Greenland.

PubMed

Augustussen, Mikaela; Sjøgren, Per; Timm, Helle; Hounsgaard, Lise; Pedersen, Michael Lynge

2017-06-01

The aims were to describe symptoms and health-related quality of life (HRQoL) in Greenlandic patients with advanced cancer and to assess the applicability and internal consistency of the Greenlandic version of the EORTC-QLQ-C30 core version 3.0. A Greenlandic version of the EORTC QLQ-C30 v.3.0 was developed. The translation process included independent forward translation, reconciliation and independent back translation by native Greenlandic-speaking translators who were fluent in English. After pilot testing, a population-based cross-sectional study of patients with advanced cancer receiving palliative treatment was conducted. Internal consistency was examined by calculating Cronbach's alpha coefficients for five function scales and three symptom scales. Of the 58 patients who participated in the study, 47% had reduced social functioning, 36% had reduced physical and role functioning and 19% had reduced emotional and cognitive functioning. Furthermore, 48% reported fatigue, and 33% reported financial problems. The Greenlandic version of the EORTC had good applicability in the assessment of symptoms and quality of life. Acceptable Cronbach's alpha coefficients (above 0.70) were observed for the physical, role and social functioning scales, the fatigue scale and the global health status scale. Patients with undergoing palliative treatment in Greenland for advanced cancer reported high levels of social and financial problems and reduced physical functioning. This indicates a potential for improving palliative care service and increasing the focus on symptom management. The Greenlandic version of the EORTC-QLQ-C30 represents an applicable and reliable tool to describe symptoms and health-related quality of life among Greenlandic patients with advanced cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Uncertainty of Polarized Parton Distributions

NASA Astrophysics Data System (ADS)

Hirai, M.; Goto, Y.; Horaguchi, T.; Kobayashi, H.; Kumano, S.; Miyama, M.; Saito, N.; Shibata, T.-A.

Polarized parton distribution functions are determined by a χ2 analysis of polarized deep inelastic experimental data. In this paper, uncertainty of obtained distribution functions is investigated by a Hessian method. We find that the uncertainty of the polarized gluon distribution is fairly large. Then, we estimate the gluon uncertainty by including the fake data which are generated from prompt photon process at RHIC. We observed that the uncertainty could be reduced with these data.

Models of community care for severe mental illness: a review of research on case management.

PubMed

Mueser, K T; Bond, G R; Drake, R E; Resnick, S G

1998-01-01

We describe different models of community care for persons with severe mental illness and review the research literature on case management, including the results of 75 studies. Most research has been conducted on the assertive community treatment (ACT) or intensive case management (ICM) models. Controlled research on ACT and ICM indicates that these models reduce time in the hospital and improve housing stability, especially among patients who are high service users. ACT and ICM appear to have moderate effects on improving symptomatology and quality of life. Most studies suggest little effect of ACT and ICM on social functioning, arrests and time spent in jail, or vocational functioning. Studies on reducing or withdrawing ACT or ICM services suggest some deterioration in gains. Research on other models of community care is inconclusive. We discuss the implications of the findings in terms of the need for specialization of ACT or ICM teams to address social and vocational functioning and substance abuse. We suggest directions for future research on models of community care, including evaluating implementation fidelity, exploring patient predictors of improvement, and evaluating the role of the helping alliance in mediating outcome.

Ghrelin and the cardiovascular system.

PubMed

Tokudome, Takeshi; Kishimoto, Ichiro; Miyazato, Mikiya; Kangawa, Kenj

2014-01-01

Ghrelin is a peptide that was originally isolated from the stomach. It exerts potent growth hormone (GH)-releasing and orexigenic activities. Several studies have highlighted the therapeutic benefits of ghrelin for the treatment of cardiovascular disease. In animal models of chronic heart failure, the administration of ghrelin improved cardiac function and remodeling; these findings were replicated in human patients with heart failure. Moreover, in an animal study, ghrelin administration effectively reduced pulmonary hypertension induced by chronic hypoxia. In addition, repeated administration of ghrelin to cachectic patients with chronic obstructive pulmonary disease had positive effects on overall body function, including muscle wasting, functional capacity and sympathetic activity. The administration of ghrelin early after myocardial infarction (MI) reduced fatal arrhythmia and related mortality. In ghrelin-deficient mice, both exogenous and endogenous ghrelin were protective against fatal arrhythmia and promoted remodeling after MI. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system remain unclear, there are indications that its beneficial effects are mediated through both direct physiological actions, including increased GH levels, improved energy balance and direct actions on cardiovascular cells, and regulation of autonomic nervous system activity. Therefore, ghrelin is a promising novel therapeutic agent for cardiovascular disease. © 2014 S. Karger AG, Basel.

Identification of mutant phenotypes associated with loss of individual microRNAs in sensitized genetic backgrounds in Caenorhabditis elegans

PubMed Central

Brenner, John L.; Jasiewicz, Kristen L.; Fahley, Alisha F.; Kemp, Benedict J.; Abbott, Allison L.

2010-01-01

Summary MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the translation and/or the stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single gene knockouts did not result in detectable mutant phenotypes [1]. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes [2]. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways [3]. Using these two approaches, mutant phenotypes were identified for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis. PMID:20579881

The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

PubMed

Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

2016-06-01

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

PubMed

Lin, Yu-Hui; Liang, Hai-Ying; Xu, Ke; Ni, Huan-Yu; Dong, Jian; Xiao, Hui; Chang, Lei; Wu, Hai-Yin; Li, Fei; Zhu, Dong-Ya; Luo, Chun-Xia

2018-02-01

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N 1-133 , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N 1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Decreased function of survival motor neuron protein impairs endocytic pathways.

PubMed

Dimitriadi, Maria; Derdowski, Aaron; Kalloo, Geetika; Maginnis, Melissa S; O'Hern, Patrick; Bliska, Bryn; Sorkaç, Altar; Nguyen, Ken C Q; Cook, Steven J; Poulogiannis, George; Atwood, Walter J; Hall, David H; Hart, Anne C

2016-07-26

Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death.

Decreased function of survival motor neuron protein impairs endocytic pathways

PubMed Central

Dimitriadi, Maria; Derdowski, Aaron; Kalloo, Geetika; Maginnis, Melissa S.; O’Hern, Patrick; Bliska, Bryn; Sorkaç, Altar; Nguyen, Ken C. Q.; Cook, Steven J.; Poulogiannis, George; Atwood, Walter J.; Hall, David H.; Hart, Anne C.

2016-01-01

Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death. PMID:27402754

Linking Executive Function and Peer Problems from Early Childhood Through Middle Adolescence.

PubMed

Holmes, Christopher J; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

2016-01-01

Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children's Behavior Questionnaire and Child Behavior Checklist and child's performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and afterschool caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa.

Linking Executive Function and Peer Problems from Early Childhood through Middle Adolescence

PubMed Central

Holmes, Christopher J.; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

2015-01-01

Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1,164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children’s Behavior Questionnaire and Child Behavior Checklist and child’s performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and after school caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa. PMID:26096194

Exploring Fusarium head blight disease control by RNA interference

USDA-ARS?s Scientific Manuscript database

RNA interference (RNAi) technology provides a novel tool to study gene function and plant protection strategies. Fusarium graminearum is the causal agent of Fusarium head blight (FHB), which reduces crop yield and quality by producing trichothecene mycotoxins including 3-acetyl deoxynivalenol (3-ADO...

76 FR 71432 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... any correspondence submitted. FRA will summarize comments received in response to this notice in a... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

16 CFR § 1303.5 - Findings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... regulation is designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

Highly Integrated Quality Assurance – An Empirical Case

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

Drake Kirkham; Amy Powell; Lucas Rich

2011-02-01

Highly Integrated Quality Assurance – An Empirical Case Drake Kirkham1, Amy Powell2, Lucas Rich3 1Quality Manager, Radioisotope Power Systems (RPS) Program, Idaho National Laboratory, P.O. Box 1625 M/S 6122, Idaho Falls, ID 83415-6122 2Quality Engineer, RPS Program, Idaho National Laboratory 3Quality Engineer, RPS Program, Idaho National Laboratory Contact: Voice: (208) 533-7550 Email: Drake.Kirkham@inl.gov Abstract. The Radioisotope Power Systems Program of the Idaho National Laboratory makes an empirical case for a highly integrated Quality Assurance function pertaining to the preparation, assembly, testing, storage and transportation of 238Pu fueled radioisotope thermoelectric generators. Case data represents multiple campaigns including the Pluto/New Horizons mission,more » the Mars Science Laboratory mission in progress, and other related projects. Traditional Quality Assurance models would attempt to reduce cost by minimizing the role of dedicated Quality Assurance personnel in favor of either functional tasking or peer-based implementations. Highly integrated Quality Assurance adds value by placing trained quality inspectors on the production floor side-by-side with nuclear facility operators to enhance team dynamics, reduce inspection wait time, and provide for immediate, independent feedback. Value is also added by maintaining dedicated Quality Engineers to provide for rapid identification and resolution of corrective action, enhanced and expedited supply chain interfaces, improved bonded storage capabilities, and technical resources for requirements management including data package development and Certificates of Inspection. A broad examination of cost-benefit indicates highly integrated Quality Assurance can reduce cost through the mitigation of risk and reducing administrative burden thereby allowing engineers to be engineers, nuclear operators to be nuclear operators, and the cross-functional team to operate more efficiently. Applicability of this case extends to any high-value, long-term project where traceability and accountability are determining factors.« less

The antagonistic modulation of Arp2/3 activity by N-WASP, WAVE2 and PICK1 defines dynamic changes in astrocyte morphology.

PubMed

Murk, Kai; Blanco Suarez, Elena M; Cockbill, Louisa M R; Banks, Paul; Hanley, Jonathan G

2013-09-01

Astrocytes exhibit a complex, branched morphology, allowing them to functionally interact with numerous blood vessels, neighboring glial processes and neuronal elements, including synapses. They also respond to central nervous system (CNS) injury by a process known as astrogliosis, which involves morphological changes, including cell body hypertrophy and thickening of major processes. Following severe injury, astrocytes exhibit drastically reduced morphological complexity and collectively form a glial scar. The mechanistic details behind these morphological changes are unknown. Here, we investigate the regulation of the actin-nucleating Arp2/3 complex in controlling dynamic changes in astrocyte morphology. In contrast to other cell types, Arp2/3 inhibition drives the rapid expansion of astrocyte cell bodies and major processes. This intervention results in a reduced morphological complexity of astrocytes in both dissociated culture and in brain slices. We show that this expansion requires functional myosin II downstream of ROCK and RhoA. Knockdown of the Arp2/3 subunit Arp3 or the Arp2/3 activator N-WASP by siRNA also results in cell body expansion and reduced morphological complexity, whereas depleting WAVE2 specifically reduces the branching complexity of astrocyte processes. By contrast, knockdown of the Arp2/3 inhibitor PICK1 increases astrocyte branching complexity. Furthermore, astrocyte expansion induced by ischemic conditions is delayed by PICK1 knockdown or N-WASP overexpression. Our findings identify a new morphological outcome for Arp2/3 activation in restricting rather than promoting outwards movement of the plasma membrane in astrocytes. The Arp2/3 regulators PICK1, and N-WASP and WAVE2 function antagonistically to control the complexity of astrocyte branched morphology, and this mechanism underlies the morphological changes seen in astrocytes during their response to pathological insult.

On the Use of 3dB Qualification Margin for Structural Parts on Expendable Launch Vehicles

NASA Technical Reports Server (NTRS)

Yunis, Isam

2007-01-01

The standard random vibration qualification test used for Expendable Launch Vehicle components is Maximum Predicted Environment (MPE) + 6dB for a duration of 4 times the service life of the part. This can be a severe qualification test for these fatigue-sensitive structures. This paper uses flight data from several launch vehicles to establish that reducing the qualification approach to MPE+3dB for the duration of the peak environment (1x life) is valid for fatigue-sensitive structural components. Items that can be classified as fatigue-sensitive are probes, ducts, tubing, bellows, hoses, and any non-functional structure. Non-functional structure may be flight critical or carry fluid, but it cannot include any moving parts or electronics. This reduced qualification approach does not include primary or secondary structure which would be exclusively designed by peak loads, either transient or quasi-static, that are so large and of so few cycles as to make fatigue a moot point.

Capacitive Feedthroughs for Medical Implants

PubMed Central

Grob, Sven; Tass, Peter A.; Hauptmann, Christian

2016-01-01

Important technological advances in the last decades paved the road to a great success story for electrically stimulating medical implants, including cochlear implants or implants for deep brain stimulation. However, there are still many challenges in reducing side effects and improving functionality and comfort for the patient. Two of the main challenges are the wish for smaller implants on one hand, and the demand for more stimulation channels on the other hand. But these two aims lead to a conflict of interests. This paper presents a novel design for an electrical feedthrough, the so called capacitive feedthrough, which allows both reducing the size, and increasing the number of included channels. Capacitive feedthroughs combine the functionality of a coupling capacitor and an electrical feedthrough within one and the same structure. The paper also discusses the progress and the challenges of the first produced demonstrators. The concept bears a high potential in improving current feedthrough technology, and could be applied on all kinds of electrical medical implants, even if its implementation might be challenging. PMID:27660602

Capacitive Feedthroughs for Medical Implants.

PubMed

Grob, Sven; Tass, Peter A; Hauptmann, Christian

2016-01-01

Important technological advances in the last decades paved the road to a great success story for electrically stimulating medical implants, including cochlear implants or implants for deep brain stimulation. However, there are still many challenges in reducing side effects and improving functionality and comfort for the patient. Two of the main challenges are the wish for smaller implants on one hand, and the demand for more stimulation channels on the other hand. But these two aims lead to a conflict of interests. This paper presents a novel design for an electrical feedthrough, the so called capacitive feedthrough, which allows both reducing the size, and increasing the number of included channels. Capacitive feedthroughs combine the functionality of a coupling capacitor and an electrical feedthrough within one and the same structure. The paper also discusses the progress and the challenges of the first produced demonstrators. The concept bears a high potential in improving current feedthrough technology, and could be applied on all kinds of electrical medical implants, even if its implementation might be challenging.

A reduced-order model from high-dimensional frictional hysteresis

PubMed Central

Biswas, Saurabh; Chatterjee, Anindya

2014-01-01

Hysteresis in material behaviour includes both signum nonlinearities as well as high dimensionality. Available models for component-level hysteretic behaviour are empirical. Here, we derive a low-order model for rate-independent hysteresis from a high-dimensional massless frictional system. The original system, being given in terms of signs of velocities, is first solved incrementally using a linear complementarity problem formulation. From this numerical solution, to develop a reduced-order model, basis vectors are chosen using the singular value decomposition. The slip direction in generalized coordinates is identified as the minimizer of a dissipation-related function. That function includes terms for frictional dissipation through signum nonlinearities at many friction sites. Luckily, it allows a convenient analytical approximation. Upon solution of the approximated minimization problem, the slip direction is found. A final evolution equation for a few states is then obtained that gives a good match with the full solution. The model obtained here may lead to new insights into hysteresis as well as better empirical modelling thereof. PMID:24910522

What is the function of centrioles?

PubMed

Marshall, Wallace F

2007-03-01

The function of centrioles has been controversial and remains incompletely resolved. This is because centrioles, in and of themselves, do not directly perform any physiological activity. Instead, their role is only to act as a jig or breadboard onto which other functional structures can be built. Centrioles are primarily involved in forming two structures-centrosomes and cilia. Centrioles bias the position of spindle pole formation, but because spindle poles can self-organize, the function of the centriole in mitosis is not obligatory. Consequently, lack of centrioles does not generally prevent mitosis, although recent experiments suggest acentriolar spindles have reduced fidelity of chromosome segregation. In contrast, centrioles are absolutely required for the assembly of cilia, including primary cilia that act as cellular antennae. Consistent with this requirement, it is now becoming clear that many ciliary diseases, including nephronophthisis, Bardet-Biedl syndrome, Meckel Syndrome, and Oral-Facial-Digital syndrome, are caused by defects in centriole-associated proteins.

Increased premotor cortex activation in high functioning autism during action observation.

PubMed

Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

2015-04-01

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of neuromuscular and quadriceps strengthening exercise in the treatment of varus malaligned knees with medial knee osteoarthritis: a randomised controlled trial protocol.

PubMed

Bennell, Kim L; Egerton, Thorlene; Wrigley, Tim V; Hodges, Paul W; Hunt, Michael; Roos, Ewa M; Kyriakides, Mary; Metcalf, Ben; Forbes, Andrew; Ageberg, Eva; Hinman, Rana S

2011-12-05

Osteoarthritis of the knee involving predominantly the medial tibiofemoral compartment is common in older people, giving rise to pain and loss of function. Many people experience progressive worsening of the disease over time, particularly those with varus malalignment and increased medial knee joint load. Therefore, interventions that can reduce excessive medial knee loading may be beneficial in reducing the risk of structural progression. Traditional quadriceps strengthening can improve pain and function in people with knee osteoarthritis but does not appear to reduce medial knee load. A neuromuscular exercise program, emphasising optimal alignment of the trunk and lower limb joints relative to one another, as well as quality of movement performance, while dynamically and functionally strengthening the lower limb muscles, may be able to reduce medial knee load. Such a program may also be superior to traditional quadriceps strengthening with respect to improved pain and physical function because of the functional and dynamic nature. This randomised controlled trial will investigate the effect of a neuromuscular exercise program on medial knee joint loading, pain and function in individuals with medial knee joint osteoarthritis. We hypothesise that the neuromuscular program will reduce medial knee load as well as pain and functional limitations to a greater extent than a traditional quadriceps strengthening program. 100 people with medial knee pain, radiographic medial compartment osteoarthritis and varus malalignment will be recruited and randomly allocated to one of two 12-week exercise programs: quadriceps strengthening or neuromuscular exercise. Each program will involve 14 supervised exercise sessions with a physiotherapist plus four unsupervised sessions per week at home. The primary outcomes are medial knee load during walking (the peak external knee adduction moment from 3D gait analysis), pain, and self-reported physical function measured at baseline and immediately following the program. Secondary outcomes include the external knee adduction moment angular impulse, electromyographic muscle activation patterns, knee and hip muscle strength, balance, functional ability, and quality-of-life. The findings will help determine whether neuromuscular exercise is superior to traditional quadriceps strengthening regarding effects on knee load, pain and physical function in people with medial knee osteoarthritis and varus malalignment. Australian New Zealand Clinical Trials Registry reference: ACTRN12610000660088.

Comparison of neuromuscular and quadriceps strengthening exercise in the treatment of varus malaligned knees with medial knee osteoarthritis: a randomised controlled trial protocol

PubMed Central

2011-01-01

Background Osteoarthritis of the knee involving predominantly the medial tibiofemoral compartment is common in older people, giving rise to pain and loss of function. Many people experience progressive worsening of the disease over time, particularly those with varus malalignment and increased medial knee joint load. Therefore, interventions that can reduce excessive medial knee loading may be beneficial in reducing the risk of structural progression. Traditional quadriceps strengthening can improve pain and function in people with knee osteoarthritis but does not appear to reduce medial knee load. A neuromuscular exercise program, emphasising optimal alignment of the trunk and lower limb joints relative to one another, as well as quality of movement performance, while dynamically and functionally strengthening the lower limb muscles, may be able to reduce medial knee load. Such a program may also be superior to traditional quadriceps strengthening with respect to improved pain and physical function because of the functional and dynamic nature. This randomised controlled trial will investigate the effect of a neuromuscular exercise program on medial knee joint loading, pain and function in individuals with medial knee joint osteoarthritis. We hypothesise that the neuromuscular program will reduce medial knee load as well as pain and functional limitations to a greater extent than a traditional quadriceps strengthening program. Methods/Design 100 people with medial knee pain, radiographic medial compartment osteoarthritis and varus malalignment will be recruited and randomly allocated to one of two 12-week exercise programs: quadriceps strengthening or neuromuscular exercise. Each program will involve 14 supervised exercise sessions with a physiotherapist plus four unsupervised sessions per week at home. The primary outcomes are medial knee load during walking (the peak external knee adduction moment from 3D gait analysis), pain, and self-reported physical function measured at baseline and immediately following the program. Secondary outcomes include the external knee adduction moment angular impulse, electromyographic muscle activation patterns, knee and hip muscle strength, balance, functional ability, and quality-of-life. Discussion The findings will help determine whether neuromuscular exercise is superior to traditional quadriceps strengthening regarding effects on knee load, pain and physical function in people with medial knee osteoarthritis and varus malalignment. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000660088 PMID:22141334

Replacing backscattering with reduced scattering. A better formulation of reflectance function?

NASA Astrophysics Data System (ADS)

Piskozub, Jacek; McKee, David; Freda, Wlodzimierz

2014-05-01

Modern reflectance formulas all involve backscattering coefficient divided by absorption coefficient (bb/a). The backscattering (or backward scattering) coefficient describes how much of the incident radiation is scattered at angles between 90 and 180 deg. However, water leaving photons are not necessarily backscattered because it is possible for a variable fraction to exit after multiple forward scattering events. Therefore the whole angular function of scattering probability (phase function) influences the reflectance signal. This is the reason why phase functions of identical backscattering ratio may result in different reflectance values, contrary to the universally used formula. This creates the question whether there may exist a better formula using a parameter better describing phase function shape than backscattering ratio. The asymmetry parameter g (the average scattering cosine) is commonly used to parametrize phase functions. A replacement for backscattering should decrease with increasing g. Therefore, the simplest candidate to replace backscattering has the form of b(1-g), where b is the scattering coefficient. Such a parameter is well known in biomedical optics under the name of reduced scattering (sometimes transport scattering). It has even been used in parametrizing reflectance in (highly turbid) human tissues. However no attempt has been made to check its usefulness in marine optics. We perform Monte Carlo radiative transfer calculations of reflectance for multiple combinations of inherent optical properties, including different phase functions. The results are used to create a new reflectance formula as a function of reduced scattering and absorption and test its robustness to changes in phase function shape compared to the traditional bb/a formula. We discuss its usefulness as well as advantages and disadvantages compared to the traditional formulation.

Altered functional connectivity during self- and close other-reflection in patients with bipolar disorder with past psychosis and patients with schizophrenia.

PubMed

Zhang, Liwen; Vander Meer, Lisette; Opmeer, Esther M; Marsman, Jan-Bernard C; Ruhé, Henricus G; Aleman, André

2016-12-01

Disturbances in implicit self-processing have been reported both in psychotic patients with bipolar disorder (BD) and schizophrenia. It remains unclear whether these two psychotic disorders show disturbed functional connectivity during explicit self-reflection, which is associated with social functioning and illness symptoms. Therefore, we investigated functional connectivity during explicit self-reflection in BD with past psychosis and schizophrenia. Twenty-three BD-patients, 17 schizophrenia-patients and 21 health controls (HC) performed a self-reflection task, including the conditions self-reflection, close other-reflection and semantic control. Functional connectivity was investigated with generalized psycho-physiological interaction (gPPI). During self-reflection compared to semantic, BD-patients had decreased connectivity between several cortical-midline structures (CMS) nodes (i.e., anterior cingulate cortex, ventromedial prefrontal cortex), the insula and the head of the caudate while HC showed increased connectivities. Schizophrenia-patients, during close other-reflection compared to semantic, demonstrated reduced ventral-anterior insula-precuneus/posterior cingulate cortex (PCC) functional connectivity, whereas this was increased in HC. There were no differences between BD and schizophrenia during self- and close other-reflection. We propose that decreased functional connectivity between the CMS nodes/insula and head of the caudate in BD-patients may imply a reduced involvement of the motivational system during self-reflection; and the reduced functional connectivity between the ventral-anterior insula and precuneus/PCC during close other-reflection in schizophrenia-patients may subserve difficulties in information integration of autobiographical memory and emotional awareness in relation to close others. These distinctive impaired patterns of functional connectivity in BD and schizophrenia (compared to HC) deserve further investigation to determine their robustness and associations with differences in clinical presentation. Copyright © 2016 Elsevier Ltd. All rights reserved.

“The Relationship between Executive Functioning, Processing Speed and White Matter Integrity in Multiple Sclerosis”

PubMed Central

Genova, Helen M.; DeLuca, John; Chiaravalloti, Nancy; Wylie, Glenn

2014-01-01

The primary purpose of the current study was to examine the relationship between performance on executive tasks and white matter integrity, assessed by diffusion tensor imaging (DTI) in Multiple Sclerosis (MS). A second aim was to examine how processing speed affects the relationship between executive functioning and FA. This relationship was examined in two executive tasks that rely heavily on processing speed: the Color-Word Interference Test and Trail-Making Test (Delis-Kaplan Executive Function System). It was hypothesized that reduced fractional anisotropy (FA) is related to poor performance on executive tasks in MS, but that this relationship would be affected by the statistical correction of processing speed from the executive tasks. 15 healthy controls and 25 persons with MS participated. Regression analyses were used to examine the relationship between executive functioning and FA, both before and after processing speed was removed from the executive scores. Before processing speed was removed from the executive scores, reduced FA was associated with poor performance on Color-Word Interference Test and Trail-Making Test in a diffuse network including corpus callosum and superior longitudinal fasciculus. However, once processing speed was removed, the relationship between executive functions and FA was no longer significant on the Trail Making test, and significantly reduced and more localized on the Color-Word Interference Test. PMID:23777468

The Role for Dietary Omega-3 Fatty Acids Supplementation in Older Adults

PubMed Central

Molfino, Alessio; Gioia, Gianfranco; Fanelli, Filippo Rossi; Muscaritoli, Maurizio

2014-01-01

Optimal nutrition is one of the most important determinants of healthier ageing, reducing the risk of disability, maintaining mental and physical functions, and thus preserving and ensuring a better quality of life. Dietary intake and nutrient absorption decline with age, thus increasing the risk of malnutrition, morbidity and mortality. Specific nutrients, particularly long-chain omega-3 polyunsaturated fatty acids (PUFAs), might have the potential of preventing and reducing co-morbidities in older adults. Omega-3 PUFAs are able to modulate inflammation, hyperlipidemia, platelet aggregation, and hypertension. Different mechanisms contribute to these effects, including conditioning cell membrane function and composition, eicosanoid production, and gene expression. The present review analyzes the influence of omega-3 PUFAs status and intake on brain function, cardiovascular system, immune function, muscle performance and bone health in older adults. Omega-3 FAs may have substantial benefits in reducing the risk of cognitive decline in older people. The available data encourage higher intakes of omega-3 PUFAs in the diet or via specific supplements. More studies are needed to confirm the role of omega-3 FAs in maintaining bone health and preventing the loss of muscle mass and function associated with ageing. In summary, omega-3 PUFAs are now identified as potential key nutrients, safe and effective in the treatment and prevention of several negative consequences of ageing. PMID:25285409

Altered default mode, fronto-parietal and salience networks in adolescents with Internet addiction.

PubMed

Wang, Lubin; Shen, Hui; Lei, Yu; Zeng, Ling-Li; Cao, Fenglin; Su, Linyan; Yang, Zheng; Yao, Shuqiao; Hu, Dewen

2017-07-01

Internet addiction (IA) is a condition characterized by loss of control over Internet use, leading to a variety of negative psychosocial consequences. Recent neuroimaging studies have begun to identify IA-related changes in specific brain regions and connections. However, whether and how the interactions within and between the large-scale brain networks are disrupted in individuals with IA remain largely unexplored. Using group independent component analysis, we extracted five intrinsic connectivity networks (ICNs) from the resting-state fMRI data of 26 adolescents with IA and 43 controls, including the anterior and posterior default mode network (DMN), left and right fronto-parietal network (FPN), and salience network (SN). We then examined the possible group differences in the functional connectivity within each ICN and between the ICNs. We found that, compared with controls, IA subjects showed: (1) reduced inter-hemispheric functional connectivity of the right FPN, whereas increased intra-hemispheric functional connectivity of the left FPN; (2) reduced functional connectivity in the dorsal medial prefrontal cortex (mPFC) of the anterior DMN; (3) reduced functional connectivity between the SN and anterior DMN. Our findings suggest that IA is associated with imbalanced interactions among the DMN, FPN and SN, which may serve as system-level neural underpinnings for the uncontrollable Internet-using behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Abdominal binders may reduce pain and improve physical function after major abdominal surgery - a systematic review.

PubMed

Rothman, Josephine Philip; Gunnarsson, Ulf; Bisgaard, Thue

2014-11-01

Evidence for the effect of post-operative abdominal binders on post-operative pain, seroma formation, physical function, pulmonary function and increased intra-abdominal pressure among patients after surgery remains largely un-investigated. A systematic review was conducted. The PubMed, EMBASE and Cochrane databases were searched for studies on the use of abdominal binders after abdominal surgery or abdominoplasty. All types of clinical studies were included. Two independent assessors evaluated the scientific quality of the studies. The primary outcomes were pain, seroma formation and physical function. A total of 50 publications were identified; 42 publications were excluded leaving eight publications counting a total of 578 patients for analysis. Generally, the scientific quality of the studies was poor. Use of abdominal binder revealed a non-significant tendency to reduce seroma formation after laparoscopic ventral herniotomy and a non-significant reduction in pain. Physical function was improved, whereas evidence supports a beneficial effect on psychological distress after open abdominal surgery. Evidence also supports that intra-abdominal pressure increases with the use of abdominal binders. Reduction of pulmonary function during use of abdominal binders has not been revealed. Abdominal binders reduce post-operative psychological distress, but their effect on post-operative pain after laparotomy and seroma formation after ventral hernia repair remains unclear. Due to the sparse evidence and poor quality of the literature, solid conclusions may be difficult to make, and procedure-specific, high-quality randomised clinical trials are warranted.

Does dysfunction of the autonomic nervous system affect success of renal denervation in reducing blood pressure?

PubMed

Fricke, Lisa; Petroff, David; Desch, Steffen; Lurz, Philipp; Reinhardt, Sebastian; Sonnabend, Melanie; Classen, Joseph; Baum, Petra

2017-01-01

Renal denervation is an interventional approach aiming to reduce high blood pressure. Its efficacy is subject of controversial debate. We analyzed autonomic function in patients undergoing renal denervation to identify responders. A total of 21 patients with treatment-resistant hypertension scheduled for renal denervation were included. Heart rate variability, pupillary function and sympathetic skin response were examined prior to intervention. Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure readings were taken. Patients were stratified according to sympathetic nervous system function. Sympathetic activity was reduced in 12 participants (group 1) and normal or enhanced in nine patients (group 2). The mean of daytime systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95% confidence interval for difference, 1-21 mmHg, p = 0.035) and from 166 to 145 mmHg (8-34 mmHg, p = 0.005), respectively. In a linear model, blood pressure reduction was 11.3 mmHg (0.3-22 mmHg) greater in group 2 than in group 1 (p = 0.045). Patients with preexisting reduced activity of the sympathetic nervous system benefited less from renal denervation.

Alterations in conflict monitoring are related to functional connectivity in Parkinson's disease.

PubMed

Rosenberg-Katz, Keren; Maidan, Inbal; Jacob, Yael; Giladi, Nir; Mirelman, Anat; Hausdorff, Jeffrey M

2016-09-01

Patients with Parkinson's disease (PD) have difficulties in executive functions including conflict monitoring. The neural mechanisms underlying these difficulties are not yet fully understood. In order to examine the neural mechanisms related to conflict monitoring in PD, we evaluated 35 patients with PD and 20 healthy older adults while they performed a word-color Stroop paradigm in the MRI. Specifically, we focused on changes between the groups in task-related functional connectivity using psycho-physiological interaction (PPI) analysis. The anterior cingulate cortex (ACC), which is a brain node previously associated with the Stroop paradigm, was selected as the seed region for this analysis. Patients with PD, as compared to healthy controls, had reduced task-related functional connectivity between the ACC and parietal regions including the precuneus and inferior parietal lobe. This was seen only in the incongruent Stroop condition. A higher level of connectivity between the ACC and precuneus was correlated with a lower error rate in the conflicting, incongruent Stroop condition in the healthy controls, but not in the patients with PD. Furthermore, the patients also had reduced functional connectivity between the ACC and the superior frontal gyrus which was present in both the incongruent and congruent task condition. The present findings shed light on brain mechanisms that are apparently associated with specific cognitive difficulties in patients with PD. Among patients with PD, impaired conflict monitoring processing within the ACC-based fronto-parietal network may contribute to difficulties under increased executive demands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Small pixel cross-talk MTF and its impact on MWIR sensor performance

NASA Astrophysics Data System (ADS)

Goss, Tristan M.; Willers, Cornelius J.

2017-05-01

As pixel sizes reduce in the development of modern High Definition (HD) Mid Wave Infrared (MWIR) detectors the interpixel cross-talk becomes increasingly difficult to regulate. The diffusion lengths required to achieve the quantum efficiency and sensitivity of MWIR detectors are typically longer than the pixel pitch dimension, and the probability of inter-pixel cross-talk increases as the pixel pitch/diffusion length fraction decreases. Inter-pixel cross-talk is most conveniently quantified by the focal plane array sampling Modulation Transfer Function (MTF). Cross-talk MTF will reduce the ideal sinc square pixel MTF that is commonly used when modelling sensor performance. However, cross-talk MTF data is not always readily available from detector suppliers, and since the origins of inter-pixel cross-talk are uniquely device and manufacturing process specific, no generic MTF models appear to satisfy the needs of the sensor designers and analysts. In this paper cross-talk MTF data has been collected from recent publications and the development for a generic cross-talk MTF model to fit this data is investigated. The resulting cross-talk MTF model is then included in a MWIR sensor model and the impact on sensor performance is evaluated in terms of the National Imagery Interoperability Rating Scale's (NIIRS) General Image Quality Equation (GIQE) metric for a range of fnumber/ detector pitch Fλ/d configurations and operating environments. By applying non-linear boost transfer functions in the signal processing chain, the contrast losses due to cross-talk may be compensated for. Boost transfer functions, however, also reduce the signal to noise ratio of the sensor. In this paper boost function limits are investigated and included in the sensor performance assessments.

Accumulation and suppressive function of regulatory T cells in malignant ascites: Reducing their suppressive function using arsenic trioxide in vitro.

PubMed

Hu, Zilong; Hu, Shidong; Wu, Youjun; Li, Songyan; He, Changzheng; Xing, Xiaowei; Wang, Yufeng; Du, Xiaohui

2018-04-01

Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As 2 O 3 ) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro . In this study, lymphocytes were separated from malignant ascites and T-cell subsets were detected via flow cytometry. Forkhead box P3 (FoxP3) expression was assessed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. In addition, cytokines, including interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ), were measured by enzyme-linked immunosorbent assay (ELISA). Abundant Tregs were observed in ascites lymphocytes, which and exhibited a significantly increased frequency compared with that in the peripheral blood of patients. Furthermore, As 2 O 3 treatment significantly reduced Treg numbers and Foxp3 mRNA levels in vitro (P<0.05). IFN-γ levels in the supernatant of ascites-derived TILs were increased by As 2 O 3 , whereas IL-10 and TGF-β levels were significantly reduced (P<0.05). As 2 O 3 may induce selective depletion and inhibit immunosuppressive function of Tregs, and may enhance the cytotoxic activity of ascites-derived TILs.

Functional properties of nisin-carbohydrate conjugates formed by radiation induced Maillard reaction

NASA Astrophysics Data System (ADS)

Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

2012-12-01

Nisin-carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin-carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin-dextran conjugates possessed better antioxidant potential than nisin-glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry.

Calculation of the Full Scattering Amplitude without Partial Wave Decomposition II: Inclusion of Exchange

NASA Technical Reports Server (NTRS)

Shertzer, Janine; Temkin, A.

2003-01-01

As is well known, the full scattering amplitude can be expressed as an integral involving the complete scattering wave function. We have shown that the integral can be simplified and used in a practical way. Initial application to electron-hydrogen scattering without exchange was highly successful. The Schrodinger equation (SE), which can be reduced to a 2d partial differential equation (pde), was solved using the finite element method. We have now included exchange by solving the resultant SE, in the static exchange approximation, which is reducible to a pair of coupled pde's. The resultant scattering amplitudes, both singlet and triplet, calculated as a function of energy are in excellent agreement with converged partial wave results.

Reduced-order surrogate models for Green's functions in black hole spacetimes

NASA Astrophysics Data System (ADS)

Galley, Chad; Wardell, Barry

2016-03-01

The fundamental nature of linear wave propagation in curved spacetime is encoded in the retarded Green's function (or propagator). Green's functions are useful tools because almost any field quantity of interest can be computed via convolution integrals with a source. In addition, perturbation theories involving nonlinear wave propagation can be expressed in terms of multiple convolutions of the Green's function. Recently, numerical solutions for propagators in black hole spacetimes have been found that are globally valid and accurate for computing physical quantities. However, the data generated is too large for practical use because the propagator depends on two spacetime points that must be sampled finely to yield accurate convolutions. I describe how to build a reduced-order model that can be evaluated as a substitute, or surrogate, for solutions of the curved spacetime Green's function equation. The resulting surrogate accurately and quickly models the original and out-of-sample data. I discuss applications of the surrogate, including self-consistent evolutions and waveforms of extreme mass ratio binaries. Green's function surrogate models provide a new and practical way to handle many old problems involving wave propagation and motion in curved spacetimes.

Abnormal functional network connectivity among resting-state networks in children with frontal lobe epilepsy.

PubMed

Widjaja, E; Zamyadi, M; Raybaud, C; Snead, O C; Smith, M L

2013-12-01

Epilepsy is considered a disorder of neural networks. The aims of this study were to assess functional connectivity within resting-state networks and functional network connectivity across resting-state networks by use of resting-state fMRI in children with frontal lobe epilepsy and to relate changes in resting-state networks with neuropsychological function. Fifteen patients with frontal lobe epilepsy and normal MR imaging and 14 healthy control subjects were recruited. Spatial independent component analysis was used to identify the resting-state networks, including frontal, attention, default mode network, sensorimotor, visual, and auditory networks. The Z-maps of resting-state networks were compared between patients and control subjects. The relation between abnormal connectivity and neuropsychological function was assessed. Correlations from all pair-wise combinations of independent components were performed for each group and compared between groups. The frontal network was the only network that showed reduced connectivity in patients relative to control subjects. The remaining 5 networks demonstrated both reduced and increased functional connectivity within resting-state networks in patients. There was a weak association between connectivity in frontal network and executive function (P = .029) and a significant association between sensorimotor network and fine motor function (P = .004). Control subjects had 79 pair-wise independent components that showed significant temporal coherence across all resting-state networks except for default mode network-auditory network. Patients had 66 pairs of independent components that showed significant temporal coherence across all resting-state networks. Group comparison showed reduced functional network connectivity between default mode network-attention, frontal-sensorimotor, and frontal-visual networks and increased functional network connectivity between frontal-attention, default mode network-sensorimotor, and frontal-visual networks in patients relative to control subjects. We found abnormal functional connectivity within and across resting-state networks in children with frontal lobe epilepsy. Impairment in functional connectivity was associated with impaired neuropsychological function.

RhoG protein regulates platelet granule secretion and thrombus formation in mice.

PubMed

Goggs, Robert; Harper, Matthew T; Pope, Robert J; Savage, Joshua S; Williams, Christopher M; Mundell, Stuart J; Heesom, Kate J; Bass, Mark; Mellor, Harry; Poole, Alastair W

2013-11-22

Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG(-/-) platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders.

Do analgesics improve functioning in patients with chronic low back pain? An explorative triple-blinded RCT.

PubMed

Schiphorst Preuper, Henrica R; Geertzen, Jan H B; van Wijhe, Marten; Boonstra, Anne M; Molmans, Barbara H W; Dijkstra, Pieter U; Reneman, Michiel F

2014-04-01

TREATMENT of patients with chronic low back pain (CLBP) aims to reduce disability, improve functional capacity, and participation. Time contingent prescription of analgesics is a treatment modality in CLBP. The impact of analgesics on functional capacity is unknown. Aim of the study was to explore the effect of analgesics on functioning measured by functional capacity evaluation, and self-reported disability in patients with CLBP. Explorative Randomized Placebo-Controlled Clinical Trial was performed in an outpatient pain rehabilitation setting on patients waiting for rehabilitation. Included patients had low back pain lasting >3 months, visual analogue scale worst pain ≥4.0 cm, and age >18 years. Outcome measures before (T0) and after treatment (T1): functional capacity, pain intensity, Roland Morris Disability Questionnaire. T1: global perceived pain relief. Patient characteristics and psychological questionnaires were assessed. Fifty patients were included in this study and were randomly assigned to 2 weeks treatment or placebo. acetaminophen/tramadol 325 mg/37.5 mg per capsule. Dose: maximum acetaminophen 1,950 mg and tramadol 225 mg per day; treatment and placebo titrated identically. Compliance and side-effects were monitored. TREATMENT effects between groups over time were compared. One patient (treatment group) was lost to follow-up. Forty-nine patients remained in the study. TREATMENT effects in primary outcomes did not differ significantly between groups. A subgroup of 10 (42%) patients (treatment group) reported global pain relief (responders) who reduced self-reported disability (p < 0.05). Responders had significantly lower catastrophizing scores. Overall treatment effects were small and non-significant. A subgroup, however, reported improved functioning as a result of treatment. Responders had lower catastrophizing scores.

Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions.

PubMed

Padula, Maria C; Schaer, Marie; Scariati, Elisa; Maeder, Johanna; Schneider, Maude; Eliez, Stephan

2017-04-01

Large-scale brain networks play a prominent role in cognitive abilities and their activity is impaired in psychiatric disorders, such as schizophrenia. Patients with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing schizophrenia and present similar cognitive impairments, including executive functions deficits. Thus, 22q11DS represents a model for the study of neural biomarkers associated with schizophrenia. In this study, we investigated structural and functional connectivity within and between the Default Mode (DMN), the Central Executive (CEN), and the Saliency network (SN) in 22q11DS using resting-state fMRI and DTI. Furthermore, we investigated if triple network impairments were related to executive dysfunctions or the presence of psychotic symptoms. Sixty-three patients with 22q11DS and sixty-eighty controls (age 6-33 years) were included in the study. Structural connectivity between main nodes of DMN, CEN, and SN was computed using probabilistic tractography. Functional connectivity was computed as the partial correlation between the time courses extracted from each node. Structural and functional connectivity measures were then correlated to executive functions and psychotic symptom scores. Our results showed mainly reduced structural connectivity within the CEN, DMN, and SN, in patients with 22q11DS compared with controls as well as reduced between-network connectivity. Functional connectivity appeared to be more preserved, with impairments being evident only within the DMN. Structural connectivity impairments were also related to executive dysfunctions. These findings show an association between triple network structural alterations and executive deficits in patients with the microdeletion, suggesting that 22q11DS and schizophrenia share common psychopathological mechanisms. Hum Brain Mapp 38:2177-2189, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Structural Damage Prediction and Analysis for Hypervelocity Impact. BUMPERII Suggestion and Problem Reports

NASA Technical Reports Server (NTRS)

1995-01-01

In the course of preparing the SD_SURF space debris analysis code, several problems and possibilities for improvement of the BUMPERII code were documented and sent to MSFC. These suggestions and problem reports are included here as a part of the contract final report. This includes reducing BUMPERII memory requirements, compiling problems with BUMPERII, FORTRAN-lint analysis of BUMPERII, and error in function PRV in BUMPERII.

Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain

PubMed Central

Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.

2017-01-01

Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897

76 FR 70532 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... correspondence submitted. FRA will summarize comments received in response to this notice in a subsequent notice... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

75 FR 3275 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... submitted. FRA will summarize comments received in response to this notice in a subsequent notice and... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

78 FR 59086 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... correspondence submitted. FRA will summarize comments received in response to this notice in a subsequent notice... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

Smaller but Fully Functional Backshell for Cable Connector

NASA Technical Reports Server (NTRS)

Stephenson, Gregory

2009-01-01

An improved design for the backshell of a connector for a shielded, multiplewire cable reduces the size of the backshell, relative to traditional designs of backshells of otherwise identical cable connectors. Notwithstanding the reduction in size, the design provides all the functionality typically demanded of such a backshell, including (1) termination of the cable shield (that is, grounding of the shield to the backshell), (2) strain relief for the cable, and (3) protection against electromagnetic interference (EMI).

Modeling procedures for handling qualities evaluation of flexible aircraft

NASA Technical Reports Server (NTRS)

Govindaraj, K. S.; Eulrich, B. J.; Chalk, C. R.

1981-01-01

This paper presents simplified modeling procedures to evaluate the impact of flexible modes and the unsteady aerodynamic effects on the handling qualities of Supersonic Cruise Aircraft (SCR). The modeling procedures involve obtaining reduced order transfer function models of SCR vehicles, including the important flexible mode responses and unsteady aerodynamic effects, and conversion of the transfer function models to time domain equations for use in simulations. The use of the modeling procedures is illustrated by a simple example.

Residual effects of ecstasy (3,4-methylenedioxymethamphetamine) on low level visual processes.

PubMed

Murray, Elizabeth; Bruno, Raimondo; Brown, John

2012-03-01

'Ecstasy' (3,4-methylenedioxymethamphetamine) induces impaired functioning in the serotonergic system, including the occipital lobe. This study employed the 'tilt aftereffect' paradigm to operationalise the function of orientation-selective neurons among ecstasy consumers and controls as a means of investigating the role of reduced serotonin on visual orientation processing. The magnitude of the tilt aftereffect reflects the extent of lateral inhibition between orientation-selective neurons and is elicited to both 'real' contours, processed in visual cortex area V1, and illusory contours, processed in V2. The magnitude of tilt aftereffect to both contour types was examined among 19 ecstasy users (6 ecstasy only; 13 ecstasy-plus-cannabis users) and 23 matched controls (9 cannabis-only users; 14 drug-naive). Ecstasy users had a significantly greater tilt magnitude than non-users for real contours (Hedge's g = 0.63) but not for illusory contours (g = 0.20). These findings provide support for literature suggesting that residual effects of ecstasy (and reduced serotonin) impairs lateral inhibition between orientation-selective neurons in V1, which however suggests that ecstasy may not substantially affect this process in V2. Multiple studies have now demonstrated ecstasy-related deficits on basic visual functions, including orientation and motion processing. Such low-level effects may contribute to the impact of ecstasy use on neuropsychological tests of visuospatial function. Copyright © 2012 John Wiley & Sons, Ltd.

Abnormal Intrinsic Functional Hubs in Severe Male Obstructive Sleep Apnea: Evidence from a Voxel-Wise Degree Centrality Analysis.

PubMed

Li, Haijun; Li, Lan; Shao, Yi; Gong, Honghan; Zhang, Wei; Zeng, Xianjun; Ye, Chenglong; Nie, Si; Chen, Liting; Peng, Dechang

2016-01-01

Obstructive sleep apnea (OSA) has been associated with changes in brain structure and regional function in certain brain areas. However, the functional features of network organization in the whole brain remain largely uncertain. The purpose of this study was to identify the OSA-related spatial centrality distribution of the whole brain functional network and to investigate the potential altered intrinsic functional hubs. Forty male patients with newly confirmed severe OSA on polysomnography, and well-matched good sleepers, participated in this study. All participants underwent a resting-state functional MRI scan and clinical and cognitive evaluation. Voxel-wise degree centrality (DC) was measured across the whole brain, and group difference in DC was compared. The relationship between the abnormal DC value and clinical variables was assessed using a linear correlation analysis. Remarkably similar spatial distributions of the functional hubs (high DC) were found in both groups. However, OSA patients exhibited a pattern of significantly reduced regional DC in the left middle occipital gyrus, posterior cingulate cortex, left superior frontal gyrus, and bilateral inferior parietal lobule, and DC was increased in the right orbital frontal cortex, bilateral cerebellum posterior lobes, and bilateral lentiform nucleus, including the putamen, extending to the hippocampus, and the inferior temporal gyrus, which overlapped with the functional hubs. Furthermore, a linear correlation analysis revealed that the DC value in the posterior cingulate cortex and left superior frontal gyrus were positively correlated with Montreal cognitive assessment scores, The DC value in the left middle occipital gyrus and bilateral inferior parietal lobule were negatively correlated with apnea-hypopnea index and arousal index in OSA patients. Our findings suggest that OSA patients exhibited specific abnormal intrinsic functional hubs including relatively reduced and increased DC. This expands our understanding of the functional characteristics of OSA, which may provide new insights into understanding the dysfunction and pathophysiology of OSA patients.

Aging and vascular endothelial function in humans

PubMed Central

SEALS, Douglas R.; JABLONSKI, Kristen L.; DONATO, Anthony J.

2012-01-01

Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging. PMID:21244363

Gait Retraining With Real-Time Biofeedback to Reduce Knee Adduction Moment: Systematic Review of Effects and Methods Used.

PubMed

Richards, Rosie; van den Noort, Josien C; Dekker, Joost; Harlaar, Jaap

2017-01-01

To review the current literature regarding methods and effects of real-time biofeedback used as a method for gait retraining to reduce knee adduction moment (KAM), with intended application for patients with knee osteoarthritis (KOA). Searches were conducted in MEDLINE, Embase, CINAHL, SPORTDiscus, Web of Science, and Cochrane Central Register of Controlled Trials with the keywords gait, feedback, and knee osteoarthritis from inception to May 2015. Titles and abstracts were screened by 1 individual for studies aiming to reduce KAM. Full-text articles were assessed by 2 individuals against predefined criteria. Data were extracted by 1 individual according to a predefined list, including participant demographics and training methods and effects. Electronic searches resulted in 190 potentially eligible studies, from which 12 met all inclusion criteria. Within-group standardized mean differences (SMDs) for reduction of KAM in healthy controls ranged from .44 to 2.47 and from .29 to .37 in patients with KOA. In patients with KOA, improvements were reported in pain and function, with SMDs ranging from .55 to 1.16. Methods of implementation of biofeedback training varied between studies, but in healthy controls increased KAM reduction was noted with implicit, rather than explicit, instructions. This review suggests that biofeedback gait training is effective primarily for reducing KAM but also for reducing pain and improving function in patients with KOA. The review was limited by the small number of studies featuring patients with KOA and the lack of controlled studies. The results suggest there is value and a need in further researching biofeedback training for reducing KAM. Future studies should include larger cohorts of patients, long-term follow-up, and controlled trials. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A Validation of the Proposed Royal Australian Navy Standard Work Week and Naval Management Diary Using a Simulated Crew of an Armidale Class Patrol Boat

DTIC Science & Technology

2015-12-01

Reduced mental capacity, poor decision making, emotional outbursts or withdrawals, and reduced alertness are among the side effects that have been...Guide.” The guide defined fatigue as “the product of intense and prolonged emotional strain, poor and inadequate diet, strenuous physical exertion...scheduling bodily functions and periods of sleepiness and wakefulness. Circadian rhythms control numerous factors in the human body including body

Influence of Exercise on Patients with Guillain-Barré Syndrome: A Systematic Review

PubMed Central

Vincent, Pierre-Olivier; Yu, Bai He Shen; Bastien, Robin; Sweeney, Aaron

2016-01-01

Purpose: To evaluate the effects of exercise interventions on improving physical outcomes in patients with Guillain-Barré syndrome (GBS). Methods: The PubMed database was searched for articles published up to and including February 2015. Randomized controlled trials (RCTs), case reports, and quasi-experimental and single-subject designs published in English-language, peer-reviewed journals that assessed the impact of physical exercise on patients with GBS were included; study quality was assessed using Sackett's rules of evidence. Data are presented qualitatively and quantitatively using numerical values and percentages. Results: Seven articles were included in the systematic review. One RCT showed that high-intensity relative to lower intensity exercise significantly reduced disability in patients with GBS, as measured with the FIM (p<0.005, r=0.71). Overall, various types of exercise programmes improve physical outcomes such as functional mobility, cardiopulmonary function, isokinetic muscle strength, and work rate and reduce fatigue in patients with GBS. Conclusion: Because of insufficient high-quality literature, making confident conclusions about the effects of exercise interventions on physical outcomes in patients with GBS is not possible. Future research should consider using higher quality study designs to confirm the results outlined in this article. PMID:27904236

Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease.

PubMed

Sano, Toshikazu; Ousaka, Daiki; Goto, Takuya; Ishigami, Shuta; Hirai, Kenta; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2018-03-30

Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P =0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P <0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P =0.225), whereas overall patients treated by CDCs had lower incidences of late failure ( P =0.022), adverse events ( P =0.013), and catheter intervention ( P =0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P =0.036). Notably, CDC infusion reduced mortality ( P =0.038) and late complications ( P <0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750. © 2018 American Heart Association, Inc.

Adolescent drinking and brain morphometry: A co-twin control analysis.

PubMed

Wilson, Sylia; Malone, Stephen M; Thomas, Kathleen M; Iacono, William G

2015-12-01

Developmental changes in structure and functioning are thought to make the adolescent brain particularly sensitive to the negative effects of alcohol. Although alcohol use disorders are relatively rare in adolescence, the initiation of alcohol use, including problematic use, becomes increasingly prevalent during this period. The present study examined associations between normative drinking (alcohol initiation, binge drinking, intoxication) and brain morphometry in a sample of 96 adolescent monozygotic twins. A priori regions of interest included 11 subcortical and 20 cortical structures implicated in the existing empirical literature as associated with normative alcohol use in adolescence. In addition, co-twin control analyses were used to disentangle risk for alcohol use from consequences of alcohol exposure on the developing brain. Results indicated significant associations reflecting preexisting vulnerability toward problematic alcohol use, including reduced volume of the amygdala, increased volume of the cerebellum, and reduced cortical volume and thickness in several frontal and temporal regions, including the superior and middle frontal gyri, pars triangularis, and middle and inferior temporal gyri. Results also indicated some associations consistent with a neurotoxic effect of alcohol exposure, including reduced volume of the ventral diencephalon and the middle temporal gyrus. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multiple Roles of Integrin-Linked Kinase in Epidermal Development, Maturation and Pigmentation Revealed by Molecular Profiling

PubMed Central

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E.; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function. PMID:22574216

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

PubMed

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

MoSwi6, an APSES family transcription factor, interacts with MoMps1 and is required for hyphal and conidial morphogenesis, appressorial function, and pathogenicity of Magnaporthe oryzae

PubMed Central

Qi, Zhongqiang; Wang, Qi; Dou, Xianying; Wang, Wei; Zhao, Qian; Lv, Ruili; Zhang, Haifeng; Zheng, Xiaobo; Wang, Ping; Zhang, Zhengguang

2011-01-01

Magnaporthe oryzae MAPK MoMps1 plays a critical role in regulating various developmental processes including cell wall integrity, stress responses, and pathogenicity. To identify potential effectors of MoMps1, we characterized the function of MoSwi6, a homolog of Saccharomyces cerevisiae Swi6 downstream of MAPK Slt2 signaling. MoSwi6 interacted with MoMps1 both in vivo and in vitro, suggesting a possible functional link analogous to Swi6-Slt2 in S. cerevisiae. Targeted gene disruption of MoSWI6 resulted in multiple developmental defects, including reduced hyphal growth, abnormal formation of conidia and appressoria, and impaired appressorium function. The reduction in appressorial turgor pressure also contributed to an attenuation of pathogenicity. The ΔMoswi6 mutant also displayed a defect in cell wall integrity, was hypersensitive to the oxidative stress, and showed significant reduction in transcription and activities of extracellular enzymes including peroxidases and laccases. Collectively, these roles are similar to those of MoMps1, confirming that MoSwi6 functions in the MoMps1 pathway to govern growth, development, and full pathogenicity. PMID:22321443

Effects of a Summer Treatment Program on Functional Sports Outcomes in Young Children with ADHD

PubMed Central

Fabiano, Gregory A.; Waschbusch, Daniel A.; Belin, Peter J.; Gnagy, Elizabeth M.; Pelham, William E.; Greiner, Andrew R.; Roemmich, James N.

2015-01-01

Participation in youth sports can be very beneficial, but children with Attention Deficit Hyperactivity Disorder (ADHD) may participate less often and less successfully. The current study evaluated functional sports outcomes for children with ADHD who attended an intensive behavioral treatment program that included a sports training component, and it compared outcomes to children with ADHD who did not attend the program. Results suggest that treatment resulted in significant improvements in many aspects of children’s sports functioning, including knowledge of game rules, in vivo game performance, and fundamental skill tasks (motor proficiency, ability to trap a soccer ball appropriately, reduced handball penalties in soccer, and improved ability to catch a baseball). Parents also reported improved sports skills and good sportsmanship in the treatment group. No differences between groups were evident on additional skill tasks evaluating accurately kicking a soccer ball, throwing a baseball, or hitting a baseball off a tee. These results suggest intensive behavioral intervention that includes sports training can significantly improve functional sports outcomes for young children with ADHD. PMID:24362766

Preserving Lagrangian Structure in Nonlinear Model Reduction with Application to Structural Dynamics

DOE PAGES

Carlberg, Kevin; Tuminaro, Ray; Boggs, Paul

2015-03-11

Our work proposes a model-reduction methodology that preserves Lagrangian structure and achieves computational efficiency in the presence of high-order nonlinearities and arbitrary parameter dependence. As such, the resulting reduced-order model retains key properties such as energy conservation and symplectic time-evolution maps. We focus on parameterized simple mechanical systems subjected to Rayleigh damping and external forces, and consider an application to nonlinear structural dynamics. To preserve structure, the method first approximates the system's “Lagrangian ingredients''---the Riemannian metric, the potential-energy function, the dissipation function, and the external force---and subsequently derives reduced-order equations of motion by applying the (forced) Euler--Lagrange equation with thesemore » quantities. Moreover, from the algebraic perspective, key contributions include two efficient techniques for approximating parameterized reduced matrices while preserving symmetry and positive definiteness: matrix gappy proper orthogonal decomposition and reduced-basis sparsification. Our results for a parameterized truss-structure problem demonstrate the practical importance of preserving Lagrangian structure and illustrate the proposed method's merits: it reduces computation time while maintaining high accuracy and stability, in contrast to existing nonlinear model-reduction techniques that do not preserve structure.« less

Preserving Lagrangian Structure in Nonlinear Model Reduction with Application to Structural Dynamics

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

Carlberg, Kevin; Tuminaro, Ray; Boggs, Paul

Our work proposes a model-reduction methodology that preserves Lagrangian structure and achieves computational efficiency in the presence of high-order nonlinearities and arbitrary parameter dependence. As such, the resulting reduced-order model retains key properties such as energy conservation and symplectic time-evolution maps. We focus on parameterized simple mechanical systems subjected to Rayleigh damping and external forces, and consider an application to nonlinear structural dynamics. To preserve structure, the method first approximates the system's “Lagrangian ingredients''---the Riemannian metric, the potential-energy function, the dissipation function, and the external force---and subsequently derives reduced-order equations of motion by applying the (forced) Euler--Lagrange equation with thesemore » quantities. Moreover, from the algebraic perspective, key contributions include two efficient techniques for approximating parameterized reduced matrices while preserving symmetry and positive definiteness: matrix gappy proper orthogonal decomposition and reduced-basis sparsification. Our results for a parameterized truss-structure problem demonstrate the practical importance of preserving Lagrangian structure and illustrate the proposed method's merits: it reduces computation time while maintaining high accuracy and stability, in contrast to existing nonlinear model-reduction techniques that do not preserve structure.« less

The Effects of Instructional Interventions Related to Street Crossing and Individuals with Disabilities

ERIC Educational Resources Information Center

Wright, Tessa; Wolery, Mark

2011-01-01

Adequate street crossing skills reduce the risk of injury and increase the functional independence of individuals with disabilities. This paper reviews research involving instructional interventions for street crossings with individuals with disabilities. Eight studies were included. There was evidence individuals could be taught street crossings…

Microbiology of Wind-eroded Sediments: Current Knowledge and Future Research Directions

USDA-ARS?s Scientific Manuscript database

Wind erosion is a threat to the sustainability and productivity of soils that takes place at local, regional, and global scales. Current estimates of cost of wind erosion have not included the costs associated with the loss of soil biodiversity and reduced ecosystem functions. Microorganisms carrie...

GLUTATHIONE (GSH) CONCENTRATIONS VARY WITH THE CELL CYCLE IN MATURING HAMSTER OOCYTES, ZYGOTES AND PRE-IMPLANATION EMBRYOS

EPA Science Inventory

Abstract
Glutathione (GSH) is thought to play critical roles in oocyte function including spindle maintenance and provision of reducing power needed to initiate sperm chromatin decondensation. Previous observations that GSH concentrations are higher in mature than immature o...

Reducing School Violence in Florida. Hot Topics: Usable Research.

ERIC Educational Resources Information Center

Kadel, Stephanie; Follman, Joseph

Violence pervades schools across the nation, disrupting school functioning and preventing students and teachers from learning and teaching. The most effective crisis management and response strategies are designed by a school team that includes administrators, faculty and staff, students, parents, bus drivers and other support staff, as well as…

ELECTRORETINOGRAMS ARE ALTERED BY SUBCHRONIC TOLUENE EXPOSURE TO LONG EVANS RATS: EXPERIMENTAL EVIDENCE SUPPORTING OBSERVATIONS FROM STUDIES OF EXPOSED HUMANS

EPA Science Inventory

Impaired visual functions, including low contrast sensitivity and reduced color discrimination, have been reported in studies of humans chronically exposed to several volatile organic solvents. These reports remain controversial, however, in part due to a lack of confirmation fro...

Computational Thermochemistry: Scale Factor Databases and Scale Factors for Vibrational Frequencies Obtained from Electronic Model Chemistries.

PubMed

Alecu, I M; Zheng, Jingjing; Zhao, Yan; Truhlar, Donald G

2010-09-14

Optimized scale factors for calculating vibrational harmonic and fundamental frequencies and zero-point energies have been determined for 145 electronic model chemistries, including 119 based on approximate functionals depending on occupied orbitals, 19 based on single-level wave function theory, three based on the neglect-of-diatomic-differential-overlap, two based on doubly hybrid density functional theory, and two based on multicoefficient correlation methods. Forty of the scale factors are obtained from large databases, which are also used to derive two universal scale factor ratios that can be used to interconvert between scale factors optimized for various properties, enabling the derivation of three key scale factors at the effort of optimizing only one of them. A reduced scale factor optimization model is formulated in order to further reduce the cost of optimizing scale factors, and the reduced model is illustrated by using it to obtain 105 additional scale factors. Using root-mean-square errors from the values in the large databases, we find that scaling reduces errors in zero-point energies by a factor of 2.3 and errors in fundamental vibrational frequencies by a factor of 3.0, but it reduces errors in harmonic vibrational frequencies by only a factor of 1.3. It is shown that, upon scaling, the balanced multicoefficient correlation method based on coupled cluster theory with single and double excitations (BMC-CCSD) can lead to very accurate predictions of vibrational frequencies. With a polarized, minimally augmented basis set, the density functionals with zero-point energy scale factors closest to unity are MPWLYP1M (1.009), τHCTHhyb (0.989), BB95 (1.012), BLYP (1.013), BP86 (1.014), B3LYP (0.986), MPW3LYP (0.986), and VSXC (0.986).

Work productivity in a population-based cohort of patients with spondyloarthritis.

PubMed

Haglund, Emma; Bremander, Ann; Bergman, Stefan; Jacobsson, Lennart T H; Petersson, Ingemar F

2013-09-01

To assess work productivity and associated factors in patients with SpA. This cross-sectional postal survey included 1773 patients with SpA identified in a regional health care register. Items on presenteeism (reduced productivity at work, 0-100%, 0 = no reduction) were answered by 1447 individuals. Absenteeism was defined as register-based sick leave using data from a national register. Disease duration, disease activity (BASDAI), physical function (BASFI), health-related quality of life (EQ-5D), anxiety (HAD-a), depression (HAD-d), self-efficacy [Arthritis Self-efficacy Scale (ASES) pain and symptom], physical activity and education were also measured. Forty-five per cent reported reduced productivity at work with a mean reduction of 20% (95% CI 18, 21) and women reported a higher mean reduction than men (mean 23% vs 17%, P < 0.001). Worse quality of life, disease activity, physical function and anxiety all correlated with reduced productivity (r = 0.52-0.66, P < 0.001), while sick leave did not. Worse outcomes on the EQ-5D (β-est -9.6, P < 0.001), BASDAI (β-est 7.8, P < 0.001), BASFI (β-est 7.3, P < 0.001), ASES pain (β-est -0.5, P < 0.001) and HAD-d (β-est 3.4, P < 0.001) were associated with reduced productivity at work in patients with SpA regardless of age, gender and disease subgroup. ASES symptoms, HAD-a and education level <12 years were associated with reduced productivity but were not significant in all strata for age, gender and disease subgroup. Work productivity was reduced in patients with SpA and more so in women. Worse quality of life, disease activity, physical function, self-efficacy and depression were all associated with reduced productivity at work in patients with SpA.

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma

PubMed Central

Yates, Katherine P.; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L.; Van Natta, Mark L.; Wise, Robert A.; Szefler, Stanley J.; Sharma, Sunita; Kho, Alvin T.; Cho, Michael H.; Croteau-Chonka, Damien C.; Castaldi, Peter J.; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R.; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A.; Zeiger, Robert S.; Adkinson, N. Franklin; Williams, Paul V.; Kelly, H. William; Grasemann, Hartmut; Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.; Raby, Benjamin A.; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Silverman, Edwin K.; Tonascia, James; Strunk, Robert C.; Weiss, Scott T.

2016-01-01

Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. Measurements and Main Results: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10−9; odds ratio, 2.8; 95% confidence interval, 2.0–4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. Conclusions: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575). PMID:27367781

Apodizing functions for Fourier transform spectroscopy.

PubMed

Naylor, David A; Tahic, Margaret K

2007-11-01

Apodizing functions are used in Fourier transform spectroscopy (FTS) to reduce the magnitude of the sidelobes in the instrumental line shape (ILS), which are a direct result of the finite maximum optical path difference in the measured interferogram. Three apodizing functions, which are considered optimal in the sense of producing the smallest loss in spectral resolution for a given reduction in the magnitude of the largest sidelobe, find frequent use in FTS [J. Opt. Soc. Am.66, 259 (1976)]. We extend this series to include optimal apodizing functions corresponding to increases in the width of the ILS ranging from factors of 1.1 to 2.0 compared with its unapodized value, and we compare the results with other commonly used apodizing functions.

Methylphenidate reduces mental fatigue and improves processing speed in persons suffered a traumatic brain injury.

PubMed

Johansson, B; Wentzel, A-P; Andréll, P; Mannheimer, C; Rönnbäck, L

2015-01-01

Post-traumatic brain injury symptoms, such as mental fatigue, have considerable negative impacts on quality-of-life. In the present study the effects of methylphenidate in two different dosages were assessed with regard to mental fatigue, pain and cognitive functions in persons who had suffered a traumatic brain injury. Fifty-one subjects were included and 44 completed the study. The treatment continued for 12 weeks, including three treatment periods with no medication for 4 weeks, administration of low dose methylphenidate (up to 5 mg × 3) for 4 weeks and normal dose methylphenidate (up to 20 mg × 3) for a further 4 weeks. The patients were randomized into three groups where all groups were given all treatments. Significantly reduced mental fatigue, assessed with the Mental Fatigue Scale (MFS) and increased information processing speed (coding, WAIS-III), were detected. The SF-36 vitality and social functioning scales were also improved significantly. Pain was not reduced by methylphenidate. The positive effects of treatment were dose-dependent, with the most prominent effects being at 60 mg methylphenidate/day spread over three doses. Observed side-effects were increased blood pressure and increased heart rate. Methylphenidate was generally well-tolerated and it improved long-lasting mental fatigue and processing speed after traumatic brain injury.

Iterative and function-continuation Fourier deconvolution methods for enhancing mass spectrometer resolution

NASA Technical Reports Server (NTRS)

Ioup, J. W.; Ioup, G. E.; Rayborn, G. H., Jr.; Wood, G. M., Jr.; Upchurch, B. T.

1984-01-01

Mass spectrometer data in the form of ion current versus mass-to-charge ratio often include overlapping mass peaks, especially in low- and medium-resolution instruments. Numerical deconvolution of such data effectively enhances the resolution by decreasing the overlap of mass peaks. In this paper two approaches to deconvolution are presented: a function-domain iterative technique and a Fourier transform method which uses transform-domain function-continuation. Both techniques include data smoothing to reduce the sensitivity of the deconvolution to noise. The efficacy of these methods is demonstrated through application to representative mass spectrometer data and the deconvolved results are discussed and compared to data obtained from a spectrometer with sufficient resolution to achieve separation of the mass peaks studied. A case for which the deconvolution is seriously affected by Gibbs oscillations is analyzed.

Improvements in safety and recovery following cystectomy: reassessing the role of pre-operative bowel preparation and interventions to speed return of post-operative bowel function.

PubMed

Zaid, Harras B; Kaffenberger, Samuel D; Chang, Sam S

2013-04-01

For radical cystectomy, historical practice trends have favored the use of preoperative bowel preparations to reduce complications, including surgical site infections, ileus, and anastomotic leaks. However, emerging data has questioned this practice. Postoperative cystectomy care also remains in flux, as new pharmacologic agents that may potentiate earlier return of bowel function are studied. We review the current literature with regards to preoperative and postoperative cystectomy bowel management.

Technologies for unattended network operations

NASA Technical Reports Server (NTRS)

Jaworski, Allan; Odubiyi, Jide; Holdridge, Mark; Zuzek, John

1991-01-01

The necessary network management functions for a telecommunications, navigation and information management (TNIM) system in the framework of an extension of the ISO model for communications network management are described. Various technologies that could substantially reduce the need for TNIM network management, automate manpower intensive functions, and deal with synchronization and control at interplanetary distances are presented. Specific technologies addressed include the use of the ISO Common Management Interface Protocol, distributed artificial intelligence for network synchronization and fault management, and fault-tolerant systems engineering.

Voxel-based morphometry of auditory and speech-related cortex in stutterers.

PubMed

Beal, Deryk S; Gracco, Vincent L; Lafaille, Sophie J; De Nil, Luc F

2007-08-06

Stutterers demonstrate unique functional neural activation patterns during speech production, including reduced auditory activation, relative to nonstutterers. The extent to which these functional differences are accompanied by abnormal morphology of the brain in stutterers is unclear. This study examined the neuroanatomical differences in speech-related cortex between stutterers and nonstutterers using voxel-based morphometry. Results revealed significant differences in localized grey matter and white matter densities of left and right hemisphere regions involved in auditory processing and speech production.

Constraints on large- x parton distributions from new weak boson production and deep-inelastic scattering data

DOE PAGES

Accardi, A.; Brady, L. T.; Melnitchouk, W.; ...

2016-06-20

A new set of leading twist parton distribution functions, referred to as "CJ15", is presented, which take advantage of developments in the theoretical treatment of nuclear corrections as well as new data. The analysis includes for the first time data on the free neutron structure function from Jefferson Lab, and new high-precision charged lepton and W-boson asymmetry data from Fermilab, which significantly reduce the uncertainty on the d/u ratio at large values of x.

An Analysis of the Effects of Phenytoin in Treating Motion Sickness and the Effects of Motion Sickness on the Human Electroencephalogram

DTIC Science & Technology

1990-12-01

ears ( tinnitus ) and/or a reduced auditory acuity resulted from the dosing. These side effects have been shown to 29 occur in some subjects as a result of...examinations. 5. Complete blood count (CBC). 6. Blood biochemistry screen (Chem 18 including liver function tests). 7. Blood cholesterol and lipids . 8. Chest X...blood lipids and cholesterol, chest X-ray, urinalysis, visual acuity test, vestibular evaluation and liver function studies. Subjects will then take

Analysis of drift correction in different simulated weighing schemes

NASA Astrophysics Data System (ADS)

Beatrici, A.; Rebelo, A.; Quintão, D.; Cacais, F. L.; Loayza, V. M.

2015-10-01

In the calibration of high accuracy mass standards some weighing schemes are used to reduce or eliminate the zero drift effects in mass comparators. There are different sources for the drift and different methods for its treatment. By using numerical methods, drift functions were simulated and a random term was included in each function. The comparison between the results obtained from ABABAB and ABBA weighing series was carried out. The results show a better efficacy of ABABAB method for drift with smooth variation and small randomness.

Multiple Stressors and the Functioning of Coral Reefs.

PubMed

Harborne, Alastair R; Rogers, Alice; Bozec, Yves-Marie; Mumby, Peter J

2017-01-03

Coral reefs provide critical services to coastal communities, and these services rely on ecosystem functions threatened by stressors. By summarizing the threats to the functioning of reefs from fishing, climate change, and decreasing water quality, we highlight that these stressors have multiple, conflicting effects on functionally similar groups of species and their interactions, and that the overall effects are often uncertain because of a lack of data or variability among taxa. The direct effects of stressors on links among functional groups, such as predator-prey interactions, are particularly uncertain. Using qualitative modeling, we demonstrate that this uncertainty of stressor impacts on functional groups (whether they are positive, negative, or neutral) can have significant effects on models of ecosystem stability, and reducing uncertainty is vital for understanding changes to reef functioning. This review also provides guidance for future models of reef functioning, which should include interactions among functional groups and the cumulative effect of stressors.

Multiple Stressors and the Functioning of Coral Reefs

NASA Astrophysics Data System (ADS)

Harborne, Alastair R.; Rogers, Alice; Bozec, Yves-Marie; Mumby, Peter J.

2017-01-01

Coral reefs provide critical services to coastal communities, and these services rely on ecosystem functions threatened by stressors. By summarizing the threats to the functioning of reefs from fishing, climate change, and decreasing water quality, we highlight that these stressors have multiple, conflicting effects on functionally similar groups of species and their interactions, and that the overall effects are often uncertain because of a lack of data or variability among taxa. The direct effects of stressors on links among functional groups, such as predator-prey interactions, are particularly uncertain. Using qualitative modeling, we demonstrate that this uncertainty of stressor impacts on functional groups (whether they are positive, negative, or neutral) can have significant effects on models of ecosystem stability, and reducing uncertainty is vital for understanding changes to reef functioning. This review also provides guidance for future models of reef functioning, which should include interactions among functional groups and the cumulative effect of stressors.

Filtered molasses concentrate from sugar cane: natural functional ingredient effective in lowering the glycaemic index and insulin response of high carbohydrate foods.

PubMed

Wright, Alison G; Ellis, Timothy P; Ilag, Leodevico L

2014-12-01

An aqueous filtered molasses concentrate (FMC) sourced from sugar cane was used as a functional ingredient in a range of carbohydrate-containing foods to reduce glycaemic response. When compared to untreated controls, postprandial glucose responses in the test products were reduced 5-20%, assessed by accredited glycaemic index (GI) testing. The reduction in glucose response in the test foods was dose-dependent and directly proportional to the ratio of FMC added to the amount of available carbohydrate in the test products. The insulin response to the foods was also reduced with FMC addition as compared to untreated controls. Inclusion of FMC in test foods did not replace any formulation ingredients; it was incorporated as an additional ingredient to existing formulations. Filtered molasses concentrate, made by a proprietary and patented process, contains many naturally occurring compounds. Some of the identified compounds are known to influence carbohydrate metabolism, and include phenolic compounds, minerals and organic acids. FMC, sourced from a by-product of sugar cane processing, shows potential as a natural functional ingredient capable of modifying carbohydrate metabolism and contributing to GI reduction of processed foods and beverages.

Neuronal correlates of reduced memory performance in overweight subjects.

PubMed

Stingl, Krunoslav T; Kullmann, Stephanie; Ketterer, Caroline; Heni, Martin; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2012-03-01

There is growing evidence that excessive body weight correlates with impaired cognitive performance like executive function, attention and memory. In our study, we applied a visual working memory task to quantify associations between body weight and executive function. In total, 34 lean (BMI 22±2.1 kg/m(2)) and 34 obese (BMI 30.4±3.2 kg/m(2)) subjects were included. Magnetic brain activity and behavioral responses were recorded during a one-back visual memory task with food and non-food pictures, which were matched for color, size and complexity. Behavioral responses (reaction time and accuracy) were reduced in obese subjects independent of the stimulus category. Neuronal activity at the source level showed a positive correlation between the right dorsolateral prefrontal cortex (DLPFC) activity and BMI only for the food category. In addition, a negative correlation between BMI and neuronal activity was observed in the occipital area for both categories. Therefore we conclude that increased body weight is associated with reduced task performance and specific neuronal changes. This altered activity is probably related to executive function as well as encoding and retrieval of information. Copyright © 2011 Elsevier Inc. All rights reserved.

Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation

PubMed Central

Rohrbough, Jeffrey; Rushton, Emma; Woodruff, Elvin; Fergestad, Tim; Vigneswaran, Krishanthan; Broadie, Kendal

2007-01-01

Formation and regulation of excitatory glutamatergic synapses is essential for shaping neural circuits throughout development. In a Drosophila genetic screen for synaptogenesis mutants, we identified mind the gap (mtg), which encodes a secreted, extracellular N-glycosaminoglycan-binding protein. MTG is expressed neuronally and detected in the synaptic cleft, and is required to form the specialized transsynaptic matrix that links the presynaptic active zone with the post-synaptic glutamate receptor (GluR) domain. Null mtg embryonic mutant synapses exhibit greatly reduced GluR function, and a corresponding loss of localized GluR domains. All known post-synaptic signaling/scaffold proteins functioning upstream of GluR localization are also grossly reduced or mislocalized in mtg mutants, including the dPix–dPak–Dock cascade and the Dlg/PSD-95 scaffold. Ubiquitous or neuronally targeted mtg RNA interference (RNAi) similarly reduce post-synaptic assembly, whereas post-synaptically targeted RNAi has no effect, indicating that presynaptic MTG induces and maintains the post-synaptic pathways driving GluR domain formation. These findings suggest that MTG is secreted from the presynaptic terminal to shape the extracellular synaptic cleft domain, and that the cleft domain functions to mediate transsynaptic signals required for post-synaptic development. PMID:17901219

Pathological alteration in the choroid plexus of Alzheimer's disease: implication for new therapy approaches.

PubMed

Krzyzanowska, Agnieszka; Carro, Eva

2012-01-01

Morphological alterations of choroid plexus in Alzheimer's disease (AD) have been extensively investigated. These changes include epithelial atrophy, thickening of the basement membrane, and stroma fibrosis. As a result, synthesis, secretory, and transportation functions are significantly altered resulting in decreased cerebrospinal fluid (CSF) turnover. Recent studies discuss the potential impacts of these changes, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to the amyloid peptide. Here, we review new evidences for AD-related changes in the choroid plexus. The data suggest that the significantly altered functions of the choroid plexus contribute to the multiparametric pathogenesis of late-onset AD.

Rehabilitation interventions for pain and disability in osteoarthritis: a review of interventions including exercise, manual techniques, and assistive devices.

PubMed

Iversen, Maura Daly

2012-01-01

Osteoarthritis (OA) results in progressive destruction of articular cartilage and bone at the joint margins, leading to impairments extending far beyond the synovial joint. Rehabilitation interventions that target specific impairments and activity restrictions can help restore independence and promote healthy living. Such interventions include exercise, physical modalities (ice, heat, ultrasonography), manual techniques (mobilization and manipulation), and assistive devices. The predominance of evidence on the effects of rehabilitation interventions for knee and hip OA suggest that they afford modest pain relief, reduced disability, and improved function. Research is needed to identify the modes of exercise and the effective doses for relief of symptoms and functional limitations.

Diabetic neuropathy: mechanisms, emerging treatments, and subtypes.

PubMed

Albers, James W; Pop-Busui, Rodica

2014-08-01

Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na(+)/K(+)-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality.

Gas and Bloating

PubMed Central

2006-01-01

Gaseous symptoms including eructation, flatulence, and bloating occur as a consequence of excess gas production, altered gas transit, or abnormal perception of normal amounts of gas within the gastrointestinal tract. There are many causes of gas and bloating including aerophagia, luminal obstructive processes, carbohydrate intolerance syndromes, small intestinal bacterial overgrowth, diseases of gut motor activity, and functional bowel disorders including irritable bowel syndrome (IBS). Because of the prominence of gaseous complaints in IBS, recent investigations have focused on new insights into pathogenesis and novel therapies of bloating. The evaluation of the patient with unexplained gas and bloating relies on careful exclusion of organic disease with further characterization of the underlying condition with directed functional testing. Treatment of gaseous symptomatology should be targeted to pathophysiologic defects whenever possible. Available therapies include lifestyle alterations, dietary modifications, enzyme preparations, adsorbents and agents which reduce surface tension, treatments that alter gut flora, and drugs that modulate gut transit. PMID:28316536

Analysis characteristics determination of electrohydraulic control system operation to reduce the operation time of a powered roof support

NASA Astrophysics Data System (ADS)

Szurgacz, Dawid

2018-01-01

The article discusses basic functions of a powered roof support in a longwall unit. The support function is to provide safety by protecting mine workings against uncontrolled falling of rocks. The subject of the research includes the measures to shorten the time of roof support shifting. The roof support is adapted to transfer, in hazard conditions of rock mass tremors, dynamic loads caused by mining exploitation. The article presents preliminary research results on the time reduction of the unit advance to increase the extraction process and thus reduce operating costs. Conducted stand tests showed the ability to increase the flow for 3/2-way valve cartridges. The level of fluid flowing through the cartridges is adequate to control individual actuators.

Episodic future thinking reduces temporal discounting in healthy adolescents.

PubMed

Bromberg, Uli; Lobatcheva, Maria; Peters, Jan

2017-01-01

Episodic Future Thinking has proven efficient in reducing impulsive behavior in several adult populations. Whether it also has a beneficial impact on decision making in adolescents is not known. Here the impact of episodic future thinking on discounting behavior was investigated in a sample of healthy adolescents (n = 44, age range 13-16 years). Discounting behavior in trials including episodic future thinking was significantly less impulsive than in control trials (t = 2.74, p = .009, dz = .44). In a subsample we controlled for executive function, alcohol use and developmental measures. Neither executive function nor alcohol use but developmental measures explained variability in the effect of episodic future thinking. These findings reveal that episodic future thinking can improve adolescent decision making while the effect is to some degree modulated by developmental measures.

Modulation of rat macrophage function by the Mangifera indica L. extracts Vimang and mangiferin.

PubMed

García, D; Delgado, R; Ubeira, F M; Leiro, J

2002-05-01

Vimang is an aqueous extract of Mangiferia indica L., traditionally used in Cuba as an anti-inflammatory, analgesic and antioxidant. In the present study, we investigated the effects of Vimang and of mangiferin (a C-glucosylxanthone present in the extract) on rat macrophage functions including phagocytic activity and the respiratory burst. Both Vimang and mangiferin showed inhibitory effects on macrophage activity: (a) intraperitoneal doses of only 50-250 mg/kg markedly reduced the number of macrophages in peritoneal exudate following intraperitoneal injection of thioglycollate 5 days previously (though there was no significant effect on the proportion of macrophages in the peritoneal-exudate cell population); (b) in vitro concentrations of 0.1-100 microg/ml reduced the phagocytosis of yeasts cells by resident peritoneal and thioglycollate-elicited macrophages; (c) in vitro concentrations of 1-50 microg/ml reduced nitric oxide (NO) production by thioglycollate-elicited macrophages stimulated in vitro with lipopolysaccharide (LPS) and IFNgamma; and (d) in vitro concentrations of 1-50 microg/ml reduced the extracellular production of reactive oxygen species (ROS) by resident and thioglycollate-elicited macrophages stimulated in vitro with phorbol myristate acetate (PMA). These results suggest that components of Vimang, including the polyphenol mangiferin, have depressor effects on the phagocytic and ROS production activities of rat macrophages and, thus, that they may be of value in the treatment of diseases of immunopathological origin characterized by the hyperactivation of phagocytic cells such as certain autoimmune disorders.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

PubMed Central

Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

2016-01-01

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

Hyperspherical Sparse Approximation Techniques for High-Dimensional Discontinuity Detection

DOE PAGES

Zhang, Guannan; Webster, Clayton G.; Gunzburger, Max; ...

2016-08-04

This work proposes a hyperspherical sparse approximation framework for detecting jump discontinuities in functions in high-dimensional spaces. The need for a novel approach results from the theoretical and computational inefficiencies of well-known approaches, such as adaptive sparse grids, for discontinuity detection. Our approach constructs the hyperspherical coordinate representation of the discontinuity surface of a function. Then sparse approximations of the transformed function are built in the hyperspherical coordinate system, with values at each point estimated by solving a one-dimensional discontinuity detection problem. Due to the smoothness of the hypersurface, the new technique can identify jump discontinuities with significantly reduced computationalmore » cost, compared to existing methods. Several approaches are used to approximate the transformed discontinuity surface in the hyperspherical system, including adaptive sparse grid and radial basis function interpolation, discrete least squares projection, and compressed sensing approximation. Moreover, hierarchical acceleration techniques are also incorporated to further reduce the overall complexity. In conclusion, rigorous complexity analyses of the new methods are provided, as are several numerical examples that illustrate the effectiveness of our approach.« less

Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction

PubMed Central

Wray, D. Walter; Amann, Markus

2016-01-01

The aging process appears to be a precursor to many age-related diseases, perhaps the most impactful of which is cardiovascular disease (CVD). Heart disease, a manifestation of CVD, is the leading cause of death in the USA, and heart failure (HF), a syndrome that develops as a consequence of heart disease, now affects almost six million American. Importantly, as this is an age-related disease, this number is likely to grow along with the ever-increasing elderly population. Hallmarks of the aging process and HF patients with a reduced ejection fraction (HFrEF) include exercise intolerance, premature fatigue, and limited oxygen delivery and utilization, perhaps as a consequence of diminished peripheral vascular function. Free radicals and oxidative stress have been implicated in this peripheral vascular dysfunction, as a redox imbalance may directly impact the function of the vascular endothelium. This review aims to bring together studies that have examined the impact of oxidative stress on peripheral vascular function and oxygen delivery and utilization with both healthy aging and HFrEF. PMID:27392715

Male fertility potential alteration in rheumatic diseases: a systematic review.

PubMed

Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfa, Eloisa; Srougi, Miguel; Silva, Clovis A

2016-01-01

Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.

Functional deficit in the medial prefrontal cortex during a language comprehension task in patients with schizophrenia.

PubMed

Dollfus, Sonia; Razafimandimby, Annick; Maiza, Olivier; Lebain, Pierrick; Brazo, Perrine; Beaucousin, Virginie; Lecardeur, Laurent; Delamillieure, Pascal; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie

2008-02-01

We and others have observed that patients with schizophrenia commonly presented a reduced left recruitment in language semantic brain regions. However, most studies include patients with leftward and rightward lateralizations for language. We investigated whether a cohort comprised purely of patients with typical lateralization (leftward) presented a reduced left recruitment in semantic regions during a language comprehension task. The goal was to reduce the inter-subject variability and thus improve the resolution for studying functional abnormalities in the language network. Twenty-three patients with schizophrenia (DSM-IV) were matched with healthy subjects in age, sex, level of education and handedness. All patients exhibited leftward lateralization for language. Functional MRI was performed as subjects listened to a story comprising characters and social interactions. Functional MRI signal variations were analyzed individually and compared among groups. Although no differences were observed in the recruitment of the semantic language network, patients with schizophrenia presented significantly lower signal variations compared to controls in the medial part of the left superior frontal gyrus (MF1) (x=-6, y=58, z=20; Z(score)=5.6; p<0.001 uncorrected). This region corresponded to the Theory of Mind (ToM) network. Only 5 of the 23 patients (21.7%) and 21 of the 23 (91.3%) control subjects demonstrated a positive signal variation in this area. A left functional deficit was observed in a core region of the ToM network in patients with schizophrenia and typical lateralizations for language. This functional defect could represent a neural basis for impaired social interaction and communication in patients with schizophrenia.

Caloric restriction: Impact upon pituitary function and reproduction

PubMed Central

Martin, Bronwen; Golden, Erin; Carlson, Olga D.; Egan, Josephine M.; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

Reduced energy intake, or caloric restriction (CR), is known to extend life span and to retard age-related health decline in a number of different species, including worms, flies, fish, mice and rats. CR has been shown to reduce oxidative stress, improve insulin sensitivity, and alter neuroendocrine responses and central nervous system (CNS) function in animals. CR has particularly profound and complex actions upon reproductive health. At the reductionist level the most crucial physiological function of any organism is its capacity to reproduce. For a successful species to thrive, the balance between available energy (food) and the energy expenditure required for reproduction must be tightly linked. An ability to coordinate energy balance and fecundity involves complex interactions of hormones from both the periphery and the CNS and primarily centers upon the master endocrine gland, the anterior pituitary. In this review article we review the effects of CR on pituitary gonadotrope function and on the male and female reproductive axes. A better understanding of how dietary energy intake affects reproductive axis function and endocrine pulsatility could provide novel strategies for the prevention and management of reproductive dysfunction and its associated comorbidities. PMID:18329344

Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study.

PubMed

Rao, Amanda; Steels, Elizabeth; Inder, Warrick J; Abraham, Suzanne; Vitetta, Luis

2016-06-01

This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.

Combining self-organizing mapping and supervised affinity propagation clustering approach to investigate functional brain networks involved in motor imagery and execution with fMRI measurements.

PubMed

Zhang, Jiang; Liu, Qi; Chen, Huafu; Yuan, Zhen; Huang, Jin; Deng, Lihua; Lu, Fengmei; Zhang, Junpeng; Wang, Yuqing; Wang, Mingwen; Chen, Liangyin

2015-01-01

Clustering analysis methods have been widely applied to identifying the functional brain networks of a multitask paradigm. However, the previously used clustering analysis techniques are computationally expensive and thus impractical for clinical applications. In this study a novel method, called SOM-SAPC that combines self-organizing mapping (SOM) and supervised affinity propagation clustering (SAPC), is proposed and implemented to identify the motor execution (ME) and motor imagery (MI) networks. In SOM-SAPC, SOM was first performed to process fMRI data and SAPC is further utilized for clustering the patterns of functional networks. As a result, SOM-SAPC is able to significantly reduce the computational cost for brain network analysis. Simulation and clinical tests involving ME and MI were conducted based on SOM-SAPC, and the analysis results indicated that functional brain networks were clearly identified with different response patterns and reduced computational cost. In particular, three activation clusters were clearly revealed, which include parts of the visual, ME and MI functional networks. These findings validated that SOM-SAPC is an effective and robust method to analyze the fMRI data with multitasks.

Altered basal ganglia-cortical functional connections in frontal lobe epilepsy: A resting-state fMRI study.

PubMed

Dong, Li; Wang, Pu; Peng, Rui; Jiang, Sisi; Klugah-Brown, Benjamin; Luo, Cheng; Yao, Dezhong

2016-12-01

The purpose of this study was to investigate alterations of basal ganglia-cortical functional connections in patients with frontal lobe epilepsy (FLE). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from 19 FLE patients and 19 age- and gender-matched healthy controls. Functional connectivity (FC) analysis was used to assess the functional connections between basal ganglia and cerebral cortex. Regions of interest, including the left/right caudate, putamen, pallidum and thalamus, were selected as the seeds. Two sample t-test was used to determine the difference between patients and controls, while controlling the age, gender and head motions. Compared with controls, FLE patients demonstrated increased FCs between basal ganglia and regions including the right fusiform gyrus, the bilateral cingulate gyrus, the precuneus and anterior cingulate gyrus. Reduced FCs were mainly located in a range of brain regions including the bilateral middle occipital gyrus, the ventral frontal lobe, the right putamen, the left fusiform gyrus and right rolandic operculum. In addition, the relationships between basal ganglia-cingulate connections and durations of epilepsy were also found. The alterations of functional integrity within the basal ganglia, as well as its connections to limbic and ventral frontal areas, indicate the important roles of the basal ganglia-cortical functional connections in FLE, and provide new insights in the pathophysiological mechanism of FLE. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional components and medicinal properties of food: a review.

PubMed

Abuajah, Christian Izuchukwu; Ogbonna, Augustine Chima; Osuji, Chijioke Maduka

2015-05-01

Research has proved a relationship between functional components of food, health and well-being. Thus, functional components of food can be effectively applied in the treatment and prevention of diseases. They act simultaneously at different or identical target sites with the potential to impart physiological benefits and promotion of wellbeing including reducing the risk of cancer, cardiovascular disease, osteoporosis, inflammation, type II diabetes, and other chronic degenerative diseases, lowering of blood cholesterol, neutralization of reactive oxygen species and charged radicals, anticarcinogenic effect, low-glycaemic response, etc. Previously, it was thought that functional ingredients such as non-starchy carbohydrates including soluble and insoluble dietary fibres, fucoidan; antioxidants including polyphenols, carotenoids, tocopherols, tocotrienols, phytosterols, isoflavones, organosulphur compounds; plant sterols and soy phytoestrogens occur only in plant foods (whole grains, fruits, and vegetables) as phytochemicals. However, probiotics, prebiotics, conjugated linolenic acid, long-chain omega-3, -6 and -9-polyunsaturated fatty acids, and bioactive peptides have proved that functional components are equally available in animal products such as milk, fermented milk products and cold-water fish. The way a food is processed affects its functional components. Many processing techniques have been found to lower the concentration of functional components in food. Conversely, other techniques were found to increase them. Hence, in a time when the role of a healthy diet in preventing non-communicable diseases is well accepted, the borderline between food and medicine is becoming very thin.

Psychological health of military children: Longitudinal evaluation of a family-centered prevention program to enhance family resilience

PubMed Central

Lester, Patricia; Stein, Judith A.; Saltzman, William; Woodward, Kirsten; MacDermid, Shelley W.; Milburn, Norweeta; Mogil, Catherine; Beardslee, William

2014-01-01

Family-centered preventive interventions have been proposed as relevant to mitigating psychological health risk and promoting resilience in military families facing wartime deployment and reintegration. This study evaluates the impact of a family-centered prevention program, Families OverComing Under Stress Family Resilience Training (FOCUS), on the psychological adjustment of military children. Two primary goals include: 1) Understanding the relationships of distress among family members using a longitudinal path model to assess relations at the child and family level, and 2) Determining pathways of program impact on child adjustment. Multilevel data analysis using structural equation modeling was conducted with de-identified service delivery data from 280 families (505 children ages 3-17) in two follow-up assessments. Standardized measures included Service Member and Civilian parental distress (Brief Symptom Inventory, PTSD Checklist – Military), child adjustment (Strengths and Difficulties Questionnaire), and family functioning (McMaster Family Assessment Device). Distress was significantly related among the service member parent, civilian parent and children. FOCUS improved family functioning, which in turn significantly reduced child distress at follow-up. Salient components of improved family functioning in reducing child distress mirrored resilience processes targeted by FOCUS. These findings underscore the public health potential of family-centered prevention for military families, and suggest areas for future research. PMID:23929043

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

PubMed Central

Sripada, Rebecca K.; King, Anthony P.; Garfinkel, Sarah N.; Wang, Xin; Sripada, Chandra S.; Welsh, Robert C.; Liberzon, Israel

2012-01-01

Background Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. Methods Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. Results Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. Limitations Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD. Conclusion These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD. PMID:22313617

Potential protection of vitamin C against liver-lesioned mice.

PubMed

Su, Min; Chen, Hongqiu; Wei, Chaohe; Chen, Ning; Wu, Wei

2014-10-01

Pathologically, liver injury can result from sustained trauma to hepatocytes, including acute damage. Thus, attenuation of hepatocellular lesion may help improve liver functions. The purpose of this study was to explore the potential advantages of vitamin C (VC) intake on acutely intralesional liver in carbon tetrachloride (CCl4)-exposed mice. Here our data showed that VC supplementation contributed to ameliorated vital signs of CCl4-lesioned mice, resulting in dose-dependent reduction of hepatomegaly. VC lowered the levels of liver functional enzymes including alanine aminotransferase (ALT) and glutamic-oxaloacetic transaminase (AST) in serum, while concentration of lactic acid concentration in blood plasma was decreased. VC-administered CCl4-lesioned mice manifested increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), while the malondialdehyde (MDA) content was reduced in liver tissue. Moreover, VC consumption attenuated hepatotoxic injuries of CCl4-lesioned mice, in which the number of TNF-α positive cells was dose-dependently reduced. Furthermore, intrahepatic expression of TRL-4 mRNA, a vital inflammation-regulator, was down-regulated in VC-administered mice. Overall, we conclude that VC has the potentiality of anti-hepatotoxicity that is capable of ameliorating liver functions, speculating that therapeutic mechanism relates to normalizing metabolism and blocking inflammatory stress in the liver. Copyright © 2014 Elsevier B.V. All rights reserved.

Heat shock protein 83 plays pleiotropic roles in embryogenesis, longevity, and fecundity of the pea aphid Acyrthosiphon pisum.

PubMed

Will, Torsten; Schmidtberg, Henrike; Skaljac, Marisa; Vilcinskas, Andreas

2017-01-01

Heat shock protein 83 (HSP83) is homologous to the chaperone HSP90. It has pleiotropic functions in Drosophila melanogaster, including the control of longevity and fecundity, and facilitates morphological evolution by buffering cryptic deleterious mutations in wild populations. In the pea aphid Acyrthosiphon pisum, HSP83 expression is moderately induced by bacterial infection but upregulated more strongly in response to heat stress and fungal infection. Stress-inducible heat shock proteins are of considerable evolutionary and ecological importance because they are known to buffer environmental variation and to influence fitness under non-optimal conditions. To investigate the functions of HSP83 in viviparous aphids, we used RNA interference to attenuate its expression and studied the impact on complex parameters. The RNA interference (RNAi)-mediated depletion of HSP83 expression in A. pisum reduced both longevity and fecundity, suggesting this chaperone has an evolutionarily conserved function in insects. Surprisingly, HSP83 depletion reduced the number of viviparous offspring while simultaneously increasing the number of premature nymphs developing in the ovaries, suggesting an unexpected role in aphid embryogenesis and eclosion. The present study indicates that reduced HSP83 expression in A. pisum reveals both functional similarities and differences compared with its reported roles in holometabolous insects. Its impact on aphid lifespan, fecundity, and embryogenesis suggests a function that determines their fitness. This could be achieved by targeting different client proteins, recruiting distinct co-chaperones or transposon activation.

Physiological serum 25-hydroxyvitamin D concentrations are associated with improved thyroid function-observations from a community-based program.

PubMed

Mirhosseini, Naghmeh; Brunel, Ludovic; Muscogiuri, Giovanna; Kimball, Samantha

2017-12-01

Vitamin D deficiency has been associated with an increased risk of hypothyroidism and autoimmune thyroid disease. Our aim was to investigate the influence of vitamin D supplementation on thyroid function and anti-thyroid antibody levels. We constructed a database that included 11,017 participants in a health and wellness program that provided vitamin D supplementation to target physiological serum 25-hydroxyvitmain D [25(OH)D] concentrations (>100 nmol/L). Participant measures were compared between entry to the program (baseline) and follow-up (12 ± 3 months later) using an intent-to-treat analysis. Further, a nested case-control design was utilized to examine differences in thyroid function over 1 year in hypothyroid individuals and euthyroid controls. More than 72% of participants achieved serum 25(OH)D concentrations >100 nmol/L at follow-up, with 20% above 125 nmol/L. Hypothyroidism was detected in 2% (23% including subclinical hypothyroidism) of participants at baseline and 0.4% (or 6% with subclinical) at follow-up. Serum 25(OH)D concentrations ≥125 nmol/L were associated with a 30% reduced risk of hypothyroidism and a 32% reduced risk of elevated anti-thyroid antibodies. Hypothyroid cases were found to have higher mean serum 25(OH)D concentrations at follow-up, which was a significant positive predictor of improved thyroid function. The results of the current study suggest that optimal thyroid function might require serum 25(OH)D concentrations above 125 nmol/L. Vitamin D supplementation may offer a safe and economical approach to improve thyroid function and may provide protection from developing thyroid disease.

Sleep disturbances and reduced work functioning in depressive or anxiety disorders.

PubMed

van Mill, Josine G; Vogelzangs, Nicole; Hoogendijk, Witte J G; Penninx, Brenda W J H

2013-11-01

We aimed to examine the associations between sleep disturbances and work functioning in an epidemiologic cohort study in subjects with or without depressive or anxiety disorders. There were 707 subjects included in our analyses with depressive or anxiety disorders and 728 subjects without current depressive or anxiety disorders. Insomnia was defined as a score ≥9 using the Insomnia Rating Scale. Self-reported sleep duration was categorized in short, normal, and long (≤6, 7-9, and ≥10 h, respectively). Work absenteeism was defined as none, short (≤2 weeks), or long (>2 weeks). Work performance was defined as not impaired, reduced, or impaired. Logistic regression analyses were performed to examine the associations of sleep disturbances with work functioning. In subjects with psychopathology, insomnia and short sleep duration were significantly associated with impaired work performance (odds ratio [OR] for insomnia, 2.20; [95% confidence interval {CI}, 1.50-3.22]; OR for short sleep, 2.54 [95% CI, 1.66-3.88] compared to normal sleep duration). Insomnia (OR, 2.48 [95% CI, 1.67-3.69]) and short sleep duration (OR, 1.85 [95% CI, 1.23-2.78]) also were associated with long-term absenteeism. These findings remained the same after considering clinical characteristics including medication use and symptom severity. In subjects without psychopathology, no significant associations were found between insomnia and short sleep duration on work functioning after considering subthreshold depression symptoms. In subjects with psychopathology, sleep disturbances were negatively associated with work functioning, independent of disorder severity and use of psychotropic medication. Further research is needed to determine if treatment of sleep disturbances in subjects with psychopathology improves work functioning. Copyright © 2013 Elsevier B.V. All rights reserved.

Mice with reduced NMDA receptor expression: more consistent with autism than schizophrenia?

PubMed

Gandal, M J; Anderson, R L; Billingslea, E N; Carlson, G C; Roberts, T P L; Siegel, S J

2012-08-01

Reduced NMDA-receptor (NMDAR) function has been implicated in the pathophysiology of neuropsychiatric disease, most strongly in schizophrenia but also recently in autism spectrum disorders (ASD). To determine the direct contribution of NMDAR dysfunction to disease phenotypes, a mouse model with constitutively reduced expression of the obligatory NR1 subunit has been developed and extensively investigated. Adult NR1(neo-/-) mice show multiple abnormal behaviors, including reduced social interactions, locomotor hyperactivity, self-injury, deficits in prepulse inhibition (PPI) and sensory hypersensitivity, among others. Whereas such phenotypes have largely been interpreted in the context of schizophrenia, these behavioral abnormalities are rather non-specific and are frequently present across models of diseases characterized by negative symptom domains. This study investigated auditory electrophysiological and behavioral paradigms relevant to autism, to determine whether NMDAR hypofunction may be more consistent with adult ASD-like phenotypes. Indeed, transgenic mice showed behavioral deficits relevant to all core ASD symptoms, including decreased social interactions, altered ultrasonic vocalizations and increased repetitive behaviors. NMDAR disruption recapitulated clinical endophenotypes including reduced PPI, auditory-evoked response N1 latency delay and reduced gamma synchrony. Auditory electrophysiological abnormalities more closely resembled those seen in clinical studies of autism than schizophrenia. These results suggest that NMDAR hypofunction may be associated with a continuum of neuropsychiatric diseases, including schizophrenia and autism. Neural synchrony abnormalities suggest an imbalance of glutamatergic and GABAergic coupling and may provide a target, along with behavioral phenotypes, for preclinical screening of novel therapeutics. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

No difference in long-term trunk muscle strength, cross-sectional area, and density in patients with chronic low back pain 7 to 11 years after lumbar fusion versus cognitive intervention and exercises.

PubMed

Froholdt, Anne; Holm, Inger; Keller, Anne; Gunderson, Ragnhild B; Reikeraas, Olav; Brox, Jens I

2011-08-01

Reduced muscle strength and density observed at 1 year after lumbar fusion may deteriorate more in the long term. To compare the long-term effect of lumbar fusion and cognitive intervention and exercises on muscle strength, cross-sectional area, density, and self-rated function in patients with chronic low back pain (CLBP) and disc degeneration. Randomized controlled study with a follow-up examination at 8.5 years (range, 7-11 years). Patients with CLBP and disc degeneration randomized to either instrumented posterolateral fusion of one or both of the two lower lumbar levels or a 3-week cognitive intervention and exercise program were included. Isokinetic muscle strength was measured by a Cybex 6000 (Cybex-Lumex, Inc., Ronkonkoma, NY, USA). All patients had previous experience with the test procedure. The back extension (E) flexion (F) muscles were tested, and the E/F ratios were calculated. Cross-sectional area and density of the back muscles were measured at the L3-L4 segment by computed tomography. Patients rated their function by the General Function Score. Trunk muscle strength, cross-sectional area, density, and self-rated function. Fifty-five patients (90%) were included at long-term follow-up. There were no significant differences in cross-sectional area, density, muscle strength, or self-rated function between the two groups. The cognitive intervention and exercise group increased trunk muscle extension significantly (p<.05), and both groups performed significantly better on trunk muscle flexion tests (p<.01) at long-term follow-up. On average, self-rated function improved by 56%, cross-sectional area was reduced by 8.5%, and muscle density was reduced by 27%. Although this study did not assess the morphology of muscles likely damaged by surgery, trunk muscle strength and cross-sectional area above the surgical levels are not different between those who had lumbar fusion or cognitive intervention and exercises at 7- to 11-year follow-up. Copyright © 2011 Elsevier Inc. All rights reserved.

Mindfulness meditation improves emotion regulation and reduces drug abuse.

PubMed

Tang, Yi-Yuan; Tang, Rongxiang; Posner, Michael I

2016-06-01

The core clinical symptoms of addiction include an enhanced incentive for drug taking (craving), impaired self-control (impulsivity and compulsivity), emotional dysregulation (negative mood) and increased stress reactivity. Symptoms related to impaired self-control involve reduced activity in anterior cingulate cortex (ACC), adjacent prefrontal cortex (mPFC) and other brain areas. Behavioral training such as mindfulness meditation can increase the function of control networks including those leading to improved emotion regulation and thus may be a promising approach for the treatment of addiction. In a series of randomized controlled trials (RCTs), we tested whether increased ACC/mPFC activity is related to better self-control abilities in executive functions, emotion regulation and stress response in healthy and addicted populations. After a brief mindfulness training (Integrative Body-Mind Training, IBMT), we used the Positive and Negative Affect Schedule (PANAS) and Profile of Mood States (POMS) to measure emotion regulation, salivary cortisol for the stress response and fMRI for brain functional and DTI structural changes. Relaxation training was used to serve as an active control. In both smokers and nonsmokers, improved self-control abilities in emotion regulation and stress reduction were found after training and these changes were related to increased ACC/mPFC activity following training. Compared with nonsmokers, smokers showed reduced ACC/mPFC activity in the self-control network before training, and these deficits were ameliorated after training. These results indicate that promoting emotion regulation and improving ACC/mPFC brain activity can help for addiction prevention and treatment. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

PubMed Central

2012-01-01

Background Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. PMID:22236378

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

PubMed Central

Hurtado-Zavala, Joaquin I.; Ramachandran, Binu; Ahmed, Saheeb; Halder, Rashi; Bolleyer, Christiane; Awasthi, Ankit; Stahlberg, Markus A.; Wagener, Robin J.; Anderson, Kristin; Drenan, Ryan M.; Lester, Henry A.; Miwa, Julie M.; Staiger, Jochen F.; Fischer, Andre; Dean, Camin

2017-01-01

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine—via α2β2-containing nicotinic receptors—to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity. PMID:28722015

Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

PubMed

Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael; Moriarty, Tara J

2016-01-01

Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

Farnesyltransferase haplodeficiency reduces neuropathology and rescues cognitive function in a mouse model of Alzheimer disease.

PubMed

Cheng, Shaowu; Cao, Dongfeng; Hottman, David A; Yuan, LiLian; Bergo, Martin O; Li, Ling

2013-12-13

Isoprenoids and prenylated proteins have been implicated in the pathophysiology of Alzheimer disease (AD), including amyloid-β precursor protein metabolism, Tau phosphorylation, synaptic plasticity, and neuroinflammation. However, little is known about the relative importance of the two protein prenyltransferases, farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT), in the pathogenesis of AD. In this study, we defined the impact of deleting one copy of FT or GGT on the development of amyloid-β (Aβ)-associated neuropathology and learning/memory impairments in APPPS1 double transgenic mice, a well established model of AD. Heterozygous deletion of FT reduced Aβ deposition and neuroinflammation and rescued spatial learning and memory function in APPPS1 mice. Heterozygous deletion of GGT reduced the levels of Aβ and neuroinflammation but had no impact on learning and memory. These results document that farnesylation and geranylgeranylation play differential roles in AD pathogenesis and suggest that specific inhibition of protein farnesylation could be a potential strategy for effectively treating AD.

Effects of mutations in the Arabidopsis Cold Shock Domain Protein 3 (AtCSP3) gene on leaf cell expansion.

PubMed

Yang, Yongil; Karlson, Dale

2012-08-01

The cold shock domain is among the most evolutionarily conserved nucleic acid binding domains from prokaryotes to higher eukaryotes, including plants. Although eukaryotic cold shock domain proteins have been extensively studied as transcriptional and post-transcriptional regulators during various developmental processes, their functional roles in plants remains poorly understood. In this study, AtCSP3 (At2g17870), which is one of four Arabidopsis thaliana c old s hock domain proteins (AtCSPs), was functionally characterized. Quantitative RT-PCR analysis confirmed high expression of AtCSP3 in reproductive and meristematic tissues. A homozygous atcsp3 loss-of-function mutant exhibits an overall reduced seedling size, stunted and orbicular rosette leaves, reduced petiole length, and curled leaf blades. Palisade mesophyll cells are smaller and more circular in atcsp3 leaves. Cell size analysis indicated that the reduced size of the circular mesophyll cells appears to be generated by a reduction of cell length along the leaf-length axis, resulting in an orbicular leaf shape. It was also determined that leaf cell expansion is impaired for lateral leaf development in the atcsp3 loss-of-function mutant, but leaf cell proliferation is not affected. AtCSP3 loss-of-function resulted in a dramatic reduction of LNG1 transcript, a gene that is involved in two-dimensional leaf polarity regulation. Transient subcellular localization of AtCSP3 in onion epidermal cells confirmed a nucleocytoplasmic localization pattern. Collectively, these data suggest that AtCSP3 is functionally linked to the regulation of leaf length by affecting LNG1 transcript accumulation during leaf development. A putative function of AtCSP3 as an RNA binding protein is also discussed in relation to leaf development.

The longitudinal relationship of sexual function and androgen status in older men: the Concord Health and Ageing in Men Project.

PubMed

Hsu, Benjumin; Cumming, Robert G; Blyth, Fiona M; Naganathan, Vasi; Le Couteur, David G; Seibel, Markus J; Waite, Louise M; Handelsman, David J

2015-04-01

It is unclear whether declining sexual function in older men is a cause or consequence of reduced androgen status. Longitudinal associations were examined between reproductive hormones and sexual function in older men. Men aged 70 years and older from the Concord Health and Ageing in Men Project study were assessed at baseline (n = 1705) and 2-year follow-up (n = 1367), with a total of 1226 men included in the final analyses. At both visits, serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, and SHBG, LH, and FSH were measured by immunoassay. Sexual functions (erectile function, sexual activity, and sexual desire) were self-reported via standardized questions. In longitudinal analyses, although baseline hormones (T, DHT, E2, and E1) did not predict decline in sexual function, the decline in serum T (but not DHT, E2, or E1) over 2 years was strongly related to the change in sexual activity and desire (but not erectile function). For each 1-SD decrease in T from baseline to 2-year follow-up, there was a multivariate-adjusted odds ratio of 1.23 (95% confidence interval, 1.12-1.36) for an additional risk of further decline in sexual activity. However, the magnitude of the decrease in serum T was strikingly small (<10%). Similar associations were found for changes over 2 years in serum T and decline in sexual desire, but not for erectile function. We found a consistent association among older men followed over 2 years between the decline in sexual activity and desire, but not in erectile function, with a decrease in serum T. Although these observational findings cannot determine causality, the small magnitude of the decrease in serum T raises the hypothesis that reduced sexual function may reduce serum T rather than the reverse.

Energetics, adaptation, and adaptability.

PubMed

Ulijaszek, Stanley J

1996-01-01

Energy capture and conversion are fundamental to human existence, and over the past three decades biological anthropologists have used a number of approaches which incorporate energetics measures in studies of human population biology. Human groups can vary enormously in their energy expenditure. This review considers evidence for genetic adaptation and presents models for physiological adaptability to reduced physiological energy availability and/or negative energy balance. In industrialized populations, different aspects of energy expenditure have been shown to have a genetic component, including basal metabolic rate, habitual physical activity level, mechanical efficiency of work performance, and thermic effect of food. Metabolic adaptation to low energy intakes has been demonstrated in populations in both developing and industrialized nations. Thyroid hormone-related effects on energy metabolic responses to low physiological energy availability are unified in a model, linking energetic adaptability in physical activity and maintenance metabolism. Negative energy balance has been shown to be associated with reduced reproductive function in women experiencing seasonal environments in some developing countries. Existing models relating negative energy balance to menstrual or ovulatory function are largely descriptive, and do not propose any physiological mechanisms for this phenomenon. A model is proposed whereby reduced physiological energy availability could influence ovulatory function via low serum levels of the amino acid aspartate and reduced sympathetic nervous system activity. © 1996 Wiley-Liss, Inc. Copyright © 1996 Wiley-Liss, Inc.

Characterization of bone marrow mesenchymal stromal cells in aplastic anaemia.

PubMed

Hamzic, Edita; Whiting, Karen; Gordon Smith, Edward; Pettengell, Ruth

2015-06-01

In aplastic anaemia (AA), haemopoietic activity is significantly reduced and generally attributed to failure of haemopoietic stem cells (HSC) within the bone marrow (BM). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the BM microenvironment, including mesenchymal stromal cells (MSC). MSC involvement in the functional restriction of HSC in AA is largely unknown and therefore, the physical and functional properties of AA MSC were studied in vitro. MSC were characterized by their phenotype and ability to form adherent stromal layers. The functional properties of AA MSC were assessed through proliferative, clonogenic and cross-over culture assays. Results indicate that although AA MSC presented typical morphology and distinctive mesenchymal markers, stromal formation was reduced, with 50% of BM samples failing to produce adherent layers. Furthermore, their proliferative and clonogenic capacity was markedly decreased (P = 0·03 and P = 0·04 respectively) and the ability to sustain haemopoiesis was significantly reduced, as assessed by total cell proliferation (P = 0·032 and P = 0·019 at Week 5 and 6, respectively) and clonogenic potential of HSC (P = 0·02 at Week 6). It was concluded that the biological characteristics of AA MSC are different from those of control MSC and their in vitro haemopoiesis-supporting ability is significantly reduced. © 2015 John Wiley & Sons Ltd.

Yoga clinical research review.

PubMed

Field, Tiffany

2011-02-01

In this paper recent research is reviewed on the effects of yoga poses on psychological conditions including anxiety and depression, on pain syndromes, cardiovascular, autoimmune and immune conditions and on pregnancy. Further, the physiological effects of yoga including decreased heartrate and blood pressure and the physical effects including weight loss and increased muscle strength are reviewed. Finally, potential underlying mechanisms are proposed including the stimulation of pressure receptors leading to enhanced vagal activity and reduced cortisol. The reduction in cortisol, in turn, may contribute to positive effects such as enhanced immune function and a lower prematurity rate. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of reduced soil functionality in European vineyards

NASA Astrophysics Data System (ADS)

Costantini, Edoardo; Priori, Simone; Akca, Ehran; Castaldini, Maurizio; D'Avino, Lorenzo; Fulchin, Emma; Gagnarli, Elena; Giffard, Brice; Erdem Kiraz, Mehmet; Lagomarsino, Alessandra; Landi, Silvia; Pellegrini, Sergio; Perria, Rita; Puccioni, Sergio; Schroers, Hans-Josef; Tardaguila, Javier; Pelengić, Radojko; Simoni, Sauro; Storchi, Paolo; Tangolar, Semih

2017-04-01

Improper or excessive land preparation methods in vineyards before planting can have a considerable impact on soil functionality. They include excessive levelling and deep ploughing leading to disturbances of the natural contour of slopes and destruction, truncation and burial of soil horizons. Manipulations may significantly modify chemical, physical, biological and hydrological balance of soils. Problems that may arise from these interventions relate to the reduction of organic substances, enrichment of calcium carbonate and soluble salts, impacting development and health of grapevines. Reduced water retention capacity can lead to increased water stress during dry season, decreased water permeability and circulation of oxygen in the soil, increased runoff volume, surface erosion and landslide risk, reduced biodiversity and limitation of biochemical processes (organic matter mineralization, bioavailability of nutrients, etc.). Soil degradations can lead to the loss of soil functionality even after the planting as a result of accelerated erosion, compaction by agricultural vehicles, excessive loss of organic matter and nutrients, and the accumulation of heavy metals such as copper. In both conventional and organic vineyards, it is quite common to have areas with reduced soil functionality that have negative impact on vine health and grape production and quality. In the framework of the Core organic RESOLVE project, a study was conducted in organic vineyards showing areas with reduced and good soil functionality. Degraded soils resulted in significantly lower amounts of grapes. The chlorophyll index (SPAD) of the grapevine during veraison was significantly lower in areas of degraded soils compared with the situation in areas of the same vineyard with non-degraded soils. In general, causes of soil malfunctioning were related to a lower fertility, including reduced organic carbon, total nitrogen and cation exchange capacity, higher concentrations of carbonates, and increased stoniness in the topsoil. Degraded soils showed lower structure quality and rooting depth limited by shallow saprolite or horizon features such as compaction, scarce fertility and high content of carbonates. The soils in the non-degraded areas showed significant higher content of total nitrogen and higher carbon/nitrogen ratios, thus a better stability of organic matter. On the other hand, biological diversity and activity, monitored by different proxies (microarthropods, nematodes, enzymes, organic matter turnover by Tea bag index) in some vineyards, all managed organically, did not show any clear and significant differences between degraded and not degraded areas. Similarly, no clear difference in overall microbial diversity indices (Shannon, Simpson) and diversity evenness (Pielou) were observed between non-degraded and degraded areas. All indices were relatively high and indicative for rich occurrence of abundant and rare microbial species, high diversity and low abundance of individual species and high species evenness.

The aging mouth: differentiating normal aging from disease.

PubMed

Lamster, Ira B; Asadourian, Lynda; Del Carmen, Tessa; Friedman, Paula K

2016-10-01

Aging is the physiologic change that occurs over time. In humans, this change occurs at different rates and are related to lifestyle, environment and genetics. It can be challenging to differentiate normal aging from disease. In the oral cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping and fracture lines, and a darker color. The pulp chamber and canals are reduced in size as a result of the deposition of secondary dentin. Coronal or root caries, however, represent disease. A limited amount of periodontal attachment loss occurs in association with aging, usually manifesting as recession on the buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the population, with the peak incidence being observed at 35-40 years of age. Changes to the mucosal tissue that occur with age include reduced wound-healing capacity. However, environmental factors, such as smoking, dramatically increase the risk of mucosal pathology. Reduced salivary gland function is often seen in association with medication usage, as well as with disorders such as diabetes mellitus. Both medication use and chronic disorders are more common in older adults. Masticatory function is of particular importance for older adults. Maintenance of a nutritionally complete diet is important for avoiding sarcopenia and the frailty syndrome. Successful oral aging is associated with adequate function and comfort. A reduced, but functional, dentition of 20 teeth in occlusion has been proposed as a measure of successful oral aging. Healthy oral aging is important to healthy aging from both biological and social perspectives. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Relationship of Intellectual Functioning and Cognitive Performance to Brain Structure in Schizophrenia

PubMed Central

Wang, Lei; Gama, Clarissa S.; Barch, Deanna M.

2017-01-01

Abstract Background: Schizophrenia (SZ) is often characterized by cognitive and intellectual impairment. However, there is much heterogeneity across individuals, suggesting different trajectories of the illness. Recent findings have shown brain volume differences across subgroups of individuals with psychosis (SZ and bipolar disorder), such that those with intellectual and cognitive impairments presented evidence of early cerebral disruption, while those with cognitive but not intellectual impairments showed evidence of progressive brain abnormalities. Our aim was to investigate the relations of cognition and intellectual functioning with brain structure abnormalities in a sample of SZ compared to unaffected individuals. Methods: 92 individuals with SZ and 94 healthy controls part of the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) underwent neuropsychological assessment and structural magnetic resonance imaging (MRI). Individuals with SZ were divided into subgroups according their estimated premorbid crystallized intellectual (ePMC-IQ) and cognitive performance. Brain volumes differences were investigated across groups. Results: SZ with ePMC-IQ and cognitive impairments had reduced total brain volume (TBV), intracranial volume (ICV), TBV corrected for ICV, and cortical gray matter volume, as well as reduced cortical thickness, and insula volumes. SZ with cognitive impairment but intact ePMC-IQ showed only reduced cortical gray matter volume and cortical thickness. Conclusions: These data provide additional evidence for heterogeneity in SZ. Impairments in cognition associated with reduced ePMC-IQ were related to evidence of broad brain structural alterations, including suggestion of early cerebral disruption. In contrast, impaired cognitive functioning in the context of more intact intellectual functioning was associated with cortical alterations that may reflect neurodegeneration. PMID:27369471

Whole genome prediction and heritability of childhood asthma phenotypes.

PubMed

McGeachie, Michael J; Clemmer, George L; Croteau-Chonka, Damien C; Castaldi, Peter J; Cho, Michael H; Sordillo, Joanne E; Lasky-Su, Jessica A; Raby, Benjamin A; Tantisira, Kelan G; Weiss, Scott T

2016-12-01

While whole genome prediction (WGP) methods have recently demonstrated successes in the prediction of complex genetic diseases, they have not yet been applied to asthma and related phenotypes. Longitudinal patterns of lung function differ between asthmatics, but these phenotypes have not been assessed for heritability or predictive ability. Herein, we assess the heritability and genetic predictability of asthma-related phenotypes. We applied several WGP methods to a well-phenotyped cohort of 832 children with mild-to-moderate asthma from CAMP. We assessed narrow-sense heritability and predictability for airway hyperresponsiveness, serum immunoglobulin E, blood eosinophil count, pre- and post-bronchodilator forced expiratory volume in 1 sec (FEV 1 ), bronchodilator response, steroid responsiveness, and longitudinal patterns of lung function (normal growth, reduced growth, early decline, and their combinations). Prediction accuracy was evaluated using a training/testing set split of the cohort. We found that longitudinal lung function phenotypes demonstrated significant narrow-sense heritability (reduced growth, 95%; normal growth with early decline, 55%). These same phenotypes also showed significant polygenic prediction (areas under the curve [AUCs] 56% to 62%). Including additional demographic covariates in the models increased prediction 4-8%, with reduced growth increasing from 62% to 66% AUC. We found that prediction with a genomic relatedness matrix was improved by filtering available SNPs based on chromatin evidence, and this result extended across cohorts. Longitudinal reduced lung function growth displayed extremely high heritability. All phenotypes with significant heritability showed significant polygenic prediction. Using SNP-prioritization increased prediction across cohorts. WGP methods show promise in predicting asthma-related heritable traits.

Reduced Abd-B Hox function during kidney development results in lineage infidelity.

PubMed

Magella, Bliss; Mahoney, Robert; Adam, Mike; Potter, S Steven

2018-06-15

Hox genes can function as key drivers of segment identity, with Hox mutations in Drosophila often resulting in dramatic homeotic transformations. In addition, however, they can serve other essential functions. In mammals, the study of Hox gene roles in development is complicated by the presence of four Hox clusters with a total of 39 genes showing extensive functional overlap. In this study, in order to better understand shared core Hox functions, we examined kidney development in mice with frameshift mutations of multiple Abd-B type Hox genes. The resulting phenotypes included dramatically reduced branching morphogenesis of the ureteric bud, premature depletion of nephron progenitors and abnormal development of the stromal compartment. Most unexpected, however, we also observed a cellular level lineage infidelity in nephron segments. Scattered cells within the proximal tubules, for example, expressed genes normally expressed only in collecting ducts. Multiple combinations of inappropriate nephron segment specific marker expression were found. In some cases, cells within a tubule showed incorrect identity, while in other cases cells showed ambiguous character, with simultaneous expression of genes associated with more than one nephron segment. These results give evidence that Hox genes have an overlapping core function at the cellular level in driving and/or maintaining correct differentiation decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

Management of functional dyspepsia: state of the art and emerging therapies

PubMed Central

Yamawaki, Hiroshi; Futagami, Seiji; Wakabayashi, Mako; Sakasegawa, Noriko; Agawa, Shuhei; Higuchi, Kazutoshi; Kodaka, Yasuhiro; Iwakiri, Katsuhiko

2017-01-01

Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain–gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS. A previous study has reported that proton pump inhibitors (PPIs) and H2-blockers were equally effective in functional dyspepsia. A new drug, acotiamide, a muscarinic antagonist and cholinesterase inhibitor, has been shown to improve gastric motility in rodents and dogs, and to reduce PDS symptoms in patients in double-blind multicenter studies. The pharmacological mechanisms of acotiamide remain unknown; whether acotiamide alters gastric emptying and gastric accommodation in patients with functional dyspepsia remains an open question. Other emerging treatment options include Rikkunshito, a herbal medicine that improves gastric emptying through 5-hydroxytryptamine (5-HT)2B-mediated pharmacological action, and tricyclic antidepressants (TCAs). Different drugs are needed to accommodate the clinical symptoms and etiology in individual patients. PMID:29344328

Management of functional dyspepsia: state of the art and emerging therapies.

PubMed

Yamawaki, Hiroshi; Futagami, Seiji; Wakabayashi, Mako; Sakasegawa, Noriko; Agawa, Shuhei; Higuchi, Kazutoshi; Kodaka, Yasuhiro; Iwakiri, Katsuhiko

2018-01-01

Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS. A previous study has reported that proton pump inhibitors (PPIs) and H 2 -blockers were equally effective in functional dyspepsia. A new drug, acotiamide, a muscarinic antagonist and cholinesterase inhibitor, has been shown to improve gastric motility in rodents and dogs, and to reduce PDS symptoms in patients in double-blind multicenter studies. The pharmacological mechanisms of acotiamide remain unknown; whether acotiamide alters gastric emptying and gastric accommodation in patients with functional dyspepsia remains an open question. Other emerging treatment options include Rikkunshito, a herbal medicine that improves gastric emptying through 5-hydroxytryptamine (5-HT)2B-mediated pharmacological action, and tricyclic antidepressants (TCAs). Different drugs are needed to accommodate the clinical symptoms and etiology in individual patients.

Functional Food and Cardiovascular Disease Prevention and Treatment: A Review.

PubMed

Asgary, Sedigheh; Rastqar, Ali; Keshvari, Mahtab

2018-03-12

Cardiovascular disease (CVD) is now the leading cause of death globally and is a growing health concern. Lifestyle factors, including nutrition, play an important role in the etiology and treatment of CVD. Functional foods based on their basic nutritional functions can decrease the risk of many chronic diseases and have some physiological benefits. They contain physiologically active components either from plant or animal sources, marketed with the claim of their ability to reduce heart disease risk, focusing primarily on established risk factors, which are hyperlipidemia, diabetes, metabolic syndrome, obesity/overweight, elevated lipoprotein A level, small dense low-density lipoprotein cholesterol (LDL-C), and elevated inflammatory marker levels. Functional foods are suspected to exert their cardioprotective effects mainly through blood lipid profile level and improve hypertension control, endothelial function, platelet aggregation, and antioxidant actions. Clinical and epidemiological observations indicate that vegetable and fruit fiber, nuts and seeds, sea foods, coffee, tea, and dark chocolate have cardioprotective potential in humans, as well whole-grain products containing intact grain kernels rich in fiber and trace nutrients. They are nutritionally more important because they contain phytoprotective substances that might work synergistically to reduce cardiovascular risk. This review will focus on the reciprocal interaction between functional foods and the potential link to cardiovascular health and the possible mechanisms of action.

Reduced knee joint loading with lateral and medial wedge insoles for management of knee osteoarthritis: a protocol for a randomized controlled trial.

PubMed

Lewinson, Ryan T; Collins, Kelsey H; Vallerand, Isabelle A; Wiley, J Preston; Woodhouse, Linda J; Reimer, Raylene A; Worobets, Jay T; Herzog, Walter; Stefanyshyn, Darren J

2014-12-03

Knee osteoarthritis (OA) progression has been linked to increased peak external knee adduction moments (KAMs). Although some trials have attempted to reduce pain and improve function in OA by reducing KAMs with a wedged footwear insole intervention, KAM reduction has not been specifically controlled for in trial designs, potentially explaining the mixed results seen in the literature. Therefore, the primary purpose of this trial is to identify the effects of reduced KAMs on knee OA pain and function. Forty-six patients with radiographically confirmed diagnosis medial knee OA will be recruited for this 3 month randomized controlled trial. Recruitment will be from Alberta and surrounding areas. Eligibility criteria include being between the ages of 40 and 85 years, have knee OA primarily localized to the medial tibiofemoral compartment, based on the American College of Rheumatology diagnostic criteria and be classified as having a Kellgren-Lawrence grade of 1 to 3. Patients will visit the laboratory at baseline for testing that includes dual x-ray absorptiometry, biomechanical testing, and surveys (KOOS, PASE activity scale, UCLA activity scale, comfort visual analog scale). At baseline, patients will be randomized to either a wedged insole group to reduce KAMs, or a waitlist control group where no intervention is provided. The survey tests will be repeated at 3 months, and response to wedged insoles over 3 months will be evaluated. This study represents the first step in systematically evaluating the effects of reduced KAMs on knee OA management by using a patient-specific wedged insole prescription procedure rather than providing the same insole to all patients. The results of this trial will provide indications as to whether reduced KAMs are an effective strategy for knee OA management, and whether a personalized approach to footwear insole prescription is warranted. NCT02067208.

Optimal ex vivo expansion of neutrophils from PBSC CD34+ cells by a combination of SCF, Flt3-L and G-CSF and its inhibition by further addition of TPO.

PubMed

Tura, Olga; Barclay, G Robin; Roddie, Huw; Davies, John; Turner, Marc L

2007-10-30

Autologous mobilised peripheral blood stem cell (PBSC) transplantation is now a standard approach in the treatment of haematological diseases to reconstitute haematopoiesis following myeloablative chemotherapy. However, there remains a period of severe neutropenia and thrombocytopenia before haematopoietic reconstitution is achieved. Ex vivo expanded PBSC have been employed as an adjunct to unmanipulated HSC transplantation, but have tended to be produced using complex cytokine mixtures aimed at multilineage (neutrophil and megakaryocyte) progenitor expansion. These have been reported to reduce or abrogate neutropenia but have little major effect on thrombocytopenia. Selective megakaryocyte expansion has been to date ineffective in reducing thrombocytopenia. This study was implemented to evaluate neutrophil specific rather than multilineage ex vivo expansion of PBSC for specifically focusing on reduction or abrogation of neutropenia. CD34+ cells (PBSC) were enriched from peripheral blood mononuclear cells following G-CSF-mobilisation and cultured with different permutations of cytokines to determine optimal cytokine combinations and doses for expansion and functional differentiation and maturation of neutrophils and their progenitors. Results were assessed by cell number, morphology, phenotype and function. A simple cytokine combination, SCF + Flt3-L + G-CSF, synergised to optimally expand and mature neutrophil progenitors assessed by cell number, phenotype, morphology and function (superoxide respiratory burst measured by chemiluminescence). G-CSF appears mandatory for functional maturation. Addition of other commonly employed cytokines, IL-3 and IL-6, had no demonstrable additive effect on numbers or function compared to this optimal combination. Addition of TPO, commonly included in multilineage progenitor expansion for development of megakaryocytes, reduced the maturation of neutrophil progenitors as assessed by number, morphology and function (respiratory burst activity). Given that platelet transfusion support is available for autologous PBSC transplantation but granulocyte transfusion is generally lacking, and that multilineage expanded PBSC do not reduce thrombocytopenia, we suggest that instead of multilineage expansion selective neutrophil expansion based on this relatively simple cytokine combination might be prioritized for development for clinical use as an adjunct to unmanipulated PBSC transplantation to reduce or abrogate post-transplant neutropenia.

Role of social support in cognitive function among elders.

PubMed

Zhu, Shuzhen; Hu, Jie; Efird, Jimmy T

2012-08-01

To examine cognitive function and its relationships to demographic characteristics and social support among elders in central China. Cognitive decline is prevalent among elders. Few studies have explored the relationship between social support and cognitive function among elders. A cross-sectional, descriptive correlational study. A quasi-random, point of reference sample of 120 elders residing in central China was recruited for study. Instruments used included a: Socio-demographic Questionnaire, the Multidimensional Scale on Perceived Social Support and the Mini-Mental State Examination. Hierarchical multiple regression was performed to examine the relationships among demographic variables, social support and cognitive function. Age, education and social support accounted for 45·2% of the variance in cognitive function. Family support was the strongest predictor of cognitive function. Elders who had higher educational levels and more family support had better cognitive function. Relevance to clinical practice.  Community healthcare providers should consolidate social support among elders in China and use family support interventions to reduce or delay cognitive decline, especially among those of increased age who are illiterate. Elders who had higher educational level and more family support had better cognitive function levels. Interventions that include family support are needed to improve cognitive function among elders in China. © 2012 Blackwell Publishing Ltd.

Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

PubMed

Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

2018-04-01

Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

Experimentally reduced root–microbe interactions reveal limited plasticity in functional root traits in Acer and Quercus

USDA-ARS?s Scientific Manuscript database

Abstract. Background and Aims Interactions between roots and soil microbes are critical components of below-ground ecology. It is essential to quantify the magnitude of root trait variation both among and within species, including variation due to plasticity. In addition to contextualizing the mag...

7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Debentures and/or TCs. (iv) Arranging for the production of Offering Circulars, certificates, and such other... to determine those factors that will minimize or reduce the cost of funding Debentures. (iii) Monitor... the Secretary; (vii) Remain custodian of such other documentation as the Secretary shall direct by...

13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... periodic sales of Debentures and/or TCs. (iv) Arranging for the production of Offering Circulars... financial markets to determine those factors that will minimize or reduce the cost of funding Debentures... SBA; (vii) Remain custodian of such other documentation as SBA shall direct by written instructions...

13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Participating Securities and/or TCs. (iv) Arranging for the production of the Offering Circular, certificates... markets to determine those factors that will minimize or reduce the cost of funding Debentures or... instructions from SBA; (vii) Remain custodian of such other documentation as SBA shall direct by written...

Brief Report: Agreement between Parents and Day-Care Professionals on Early Symptoms Associated with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Larsen, Kenneth; Aasland, Astrid; Diseth, Trond H.

2018-01-01

Early identification of Autism Spectrum Disorders (ASD) has the potential to elicit effective early intervention, improving children's level of functioning and developmental trajectories as well as reducing parental stress. Multiple sources of information, including several informants may facilitate early identification. This study examined the…

The Effects of Multi-Sensory Environments on the Stereotypic Behaviors of Children with Autism

ERIC Educational Resources Information Center

Brandenburg, Linda A.

2012-01-01

A significant problem for individuals with autism is the presence of stereotypic behaviors, that is, repetitive, invariant behavior patterns with no obvious goal or function. Stereotypic behaviors interfere with an individual's ability to participate in the daily activities of life, including learning. By reducing stereotypic behaviors in…

Clinical Assessment of Functional Movement in Adults with Visual Impairments

ERIC Educational Resources Information Center

Ray, Christopher T.; Horvat, Michael; Williams, Michael; Blasch, Bruce B.

2007-01-01

Adults with visual impairments have significantly more health risks than do sighted adults because of a number of factors, including the lower mineral density of their femoral neck bones, which is indicative of reduced weight-bearing exercise; their lesser maximal strength; and their higher rates of stroke, osteoporosis, depression, hypertension,…

Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation

PubMed Central

Kang, Myung-Su; Lee, Dohyun; Lee, Seung-Hyun

2017-01-01

Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA receptor–mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD. PMID:28899869

Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation.

PubMed

Kang, Myung-Su; Choi, Tae-Yong; Ryu, Hye Guk; Lee, Dohyun; Lee, Seung-Hyun; Choi, Se-Young; Kim, Kyong-Tai

2017-10-02

Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3 -deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3 -deficient mice. These mice also exhibited a reduced rectification of AMPA receptor-mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3 -deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD. © 2017 Kang et al.

The Cytoplasmic Tail of the T Cell Receptor CD3 ε Subunit Contains a Phospholipid-Binding Motif that Regulates T Cell Functions1

PubMed Central

DeFord-Watts, Laura M.; Tassin, Tara C.; Becker, Amy M.; Medeiros, Jennifer J.; Albanesi, Joseph P.; Love, Paul E.; Wülfing, Christoph; van Oers, Nicolai S. C.

2010-01-01

The CD3 ε subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3 ε, termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 ε to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3, and PI(4,5)P2. Transgenic mice containing mutations of the BRS exhibited varying developmental defects, ranging from reduced thymic cellularity to a complete block in T cell development. Peripheral T cells from BRS-modified mice also exhibited several defects, including decreased TCR surface expression, reduced TCR-mediated signaling responses to agonist peptide-loaded APCs, and delayed CD3 ε localization to the immunological synapse. Overall, these findings demonstrate a functional role for the CD3 ε lipid-binding domain in T cell biology. PMID:19542373

High-fidelity modeling and impact footprint prediction for vehicle breakup analysis

NASA Astrophysics Data System (ADS)

Ling, Lisa

For decades, vehicle breakup analysis had been performed for space missions that used nuclear heater or power units in order to assess aerospace nuclear safety for potential launch failures leading to inadvertent atmospheric reentry. Such pre-launch risk analysis is imperative to assess possible environmental impacts, obtain launch approval, and for launch contingency planning. In order to accurately perform a vehicle breakup analysis, the analysis tool should include a trajectory propagation algorithm coupled with thermal and structural analyses and influences. Since such a software tool was not available commercially or in the public domain, a basic analysis tool was developed by Dr. Angus McRonald prior to this study. This legacy software consisted of low-fidelity modeling and had the capability to predict vehicle breakup, but did not predict the surface impact point of the nuclear component. Thus the main thrust of this study was to develop and verify the additional dynamics modeling and capabilities for the analysis tool with the objectives to (1) have the capability to predict impact point and footprint, (2) increase the fidelity in the prediction of vehicle breakup, and (3) reduce the effort and time required to complete an analysis. The new functions developed for predicting the impact point and footprint included 3-degrees-of-freedom trajectory propagation, the generation of non-arbitrary entry conditions, sensitivity analysis, and the calculation of impact footprint. The functions to increase the fidelity in the prediction of vehicle breakup included a panel code to calculate the hypersonic aerodynamic coefficients for an arbitrary-shaped body and the modeling of local winds. The function to reduce the effort and time required to complete an analysis included the calculation of node failure criteria. The derivation and development of these new functions are presented in this dissertation, and examples are given to demonstrate the new capabilities and the improvements made, with comparisons between the results obtained from the upgraded analysis tool and the legacy software wherever applicable.

Colour discrimination and categorisation in Williams syndrome.

PubMed

Farran, Emily K; Cranwell, Matthew B; Alvarez, James; Franklin, Anna

2013-10-01

Individuals with Williams syndrome (WS) present with impaired functioning of the dorsal visual stream relative to the ventral visual stream. As such, little attention has been given to ventral stream functions in WS. We investigated colour processing, a predominantly ventral stream function, for the first time in nineteen individuals with Williams syndrome. Colour discrimination was assessed using the Farnsworth-Munsell 100 hue test. Colour categorisation was assessed using a match-to-sample test and a colour naming task. A visual search task was also included as a measure of sensitivity to the size of perceptual colour difference. Results showed that individuals with WS have reduced colour discrimination relative to typically developing participants matched for chronological age; performance was commensurate with a typically developing group matched for non-verbal ability. In contrast, categorisation was typical in WS, although there was some evidence that sensitivity to the size of perceptual colour differences was reduced in this group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Novel rGO-T-C(n) Nanosheets developed via click chemistry as a lubricant anti-wear additive.

PubMed

Bagheri, Samira; Jamal, Nadia; Halilu, Ahmed; TermehYousefi, Amin

2018-04-18

Process equipment and facilities are constantly facing the dilemmas of tear and wear. This manuscript introducing functionalized reduced graphene oxide with triazole moiety via click chemistry as a anti-wear additive. While this has been achieved successfully, full characterization of the new anti-wear additive material revealed it to be promising in ameliorating issues of wears. One of the merits of the synthesized material includes reduction of contact asperity as the lipophilic alkyl chain length increases. It has been tested to be functional when formulated as an additive in group III petroleum base oil. Accordingly, it shows an irregularity in renewable base oil. Following screening evaluations of the lipophilic alkyl chain lengths, the additive with twelve carbon atoms; functionalized reduced graphene oxide, rGO-T-C(12) was confirmed to stand out among others with the good reduction of friction coefficient and the least wear scar diameter of ~539.78 µm, compared to the base oil containing no additive.

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

PubMed

Stevanovic, Ana; Schaefer, Patrick; Coburn, Mark; Rossaint, Rolf; Stoppe, Christian; Boor, Peter; Pfister, David; Heidenreich, Axel; Christ, Hildegard; Hellmich, Martin; Fahlenkamp, Astrid V

2017-01-01

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies. We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients. A prospective randomized, single-blinded, controlled study. Single-center, University Hospital of Aachen, Germany between July 2013-October 2015. Forty-six patients with regular renal function undergoing partial nephrectomy. Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia. Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months. Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months. Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon. ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular events and residual renal function in dialysis patients: a meta-analysis of randomised controlled trials.

PubMed

Liu, Youxia; Ma, Xinxin; Zheng, Jie; Jia, Junya; Yan, Tiekun

2017-06-30

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reducing risk of cardiovascular events (CVEs) and preserving kidney function in patients with chronic kidney disease is well-documented. However, the efficacy and safety of these agents in dialysis patients is still a controversial issue. We systematically searched MEDLINE, Embase, Cochrane Library and Wanfang for randomized trials. The relative risk (RR) reductions were calculated with a random-effects model. Major cardiovascular events, changes in GFR and drug-related adverse events were analyzed. Eleven trials included 1856 participants who were receiving dialysis therapy. Compared with placebo or other active agents groups, ARB therapy reduced the risk of heart failure events by 33% (RR 0.67, 95% CI 0.47 to 0.93) with similar decrement in blood pressure in dialysis patients. Indirect comparison suggested that fewer cardiovascular events happened during treatment with ARB (0.77, 0.63 to 0.94). The results indicated no significant differences between the two treatment regimens with regard to frequency of myocardial infarction (1.0, 0.45 to 2.22), stroke (1.16, 0.69 to 1.96), cardiovascular death (0.89, 0.64 to 1.26) and all-cause mortality (0.94, 0.75 to 1.17). Five studies reported the renoprotective effect and revealed that ACEI/ARB therapy significantly slowed the rate of decline in both residual renal function (MD 0.93 mL/min/1.73 m 2 , 0.38 to 1.47 mL/min/1.73 m 2 ) and urine volume (MD 167 ml, 95% CI 21 ml to 357 ml). No difference in drug-related adverse events was observed in both treatment groups. This study demonstrates that ACE-Is/ARBs therapy decreases the loss of residual renal function, mainly for patients with peritoneal dialysis. Overall, ACE-Is and ARBs do not reduce cardiovascular events in dialysis patients, however, treatment with ARB seems to reduce cardiovascular events including heart failure. ACE-Is and ARBs do not induce an extra risk of side effects.

A cross-sectional observational study comparing foot and ankle characteristics in people with stroke and healthy controls.

PubMed

Kunkel, Dorit; Potter, Julia; Mamode, Louis

2017-06-01

The purpose of this study was to explore and compare foot and ankle characteristics in people with stroke and healthy controls; and between stroke fallers and non-fallers. Participants were recruited from community groups and completed standardized tests assessing sensation, foot posture, foot function, ankle dorsiflexion and first metatarsal phalangeal joint range of motion (1st MPJ ROM), hallux valgus presence and severity. Twenty-three stroke participants (mean age 75.09 ± 7.57 years; 12 fallers) and 16 controls (mean age 73.44 ± 8.35 years) took part. Within the stroke group, reduced 1st MPJ sensation (p = 0.016) and 1st MPJ ROM (p = 0.025) were observed in the affected foot in comparison to the non-affected foot; no other differences were apparent. Pooled data (for both feet) was used to explore between stroke/control (n = 78 feet) and stroke faller/non-faller (n = 46 feet) group differences. In comparison to the control group, stroke participants exhibited reduced sensation of the 1st MPJ (p = 0.020), higher Foot Posture Index scores (indicating greater foot pronation, p = 0.008) and reduced foot function (p = 0.003). Stroke fallers exhibited significantly greater foot pronation in comparison to non-fallers (p = 0.027). Results indicated differences in foot and ankle characteristics post stroke in comparison to healthy controls. These changes may negatively impact functional ability and the ability to preserve balance. Further research is warranted to explore the influence of foot problems on balance ability and falls in people with stroke. Implications for Rehabilitation Foot problems are common post stroke. As foot problems have been linked to increased fall risk among the general population we recommend that it would be beneficial to include foot and ankle assessments or a referral to a podiatrist for people with stroke who report foot problems. Further research is needed to explore if we can improve functional performance post stroke and reduce fall risk if treatment or prevention of foot problems can be included in stroke rehabilitation.

Gender differences in functional disability and self-care among seniors in Bangladesh.

PubMed

Tareque, Md Ismail; Tiedt, Andrew D; Islam, Towfiqua Mahfuza; Begum, Sharifa; Saito, Yasuhiko

2017-08-08

Disability among older adults is a public health concern. To date there are no in-depth and comprehensive analyses on older adults' disabilities in Bangladesh. This study investigated gender differences in the prevalence of disability and the socio-demographic factors associated with disability among older adults in Bangladesh. This research used a sample of 4176 elderly males and females aged 60 years and over from a nationally representative data set- Bangladesh's 2010 Household Income and Expenditure Survey. The study used both household level and individual level data and applied a wealth index, which was constructed based on household assets using principal component analysis. The Washington Group's short set of questions on disability were used to measure disability. Chi-square tests and ordinal logistic regression models were fit. Forty-two percent of older had some form of functional disability, including 5% of elderly with severe/extreme functional disability. Seven percent of older adults had a self-care disability, including 3% of elderly with a severe/extreme form of self-care disability. Elderly females suffered from all the studied disabilities, including functional and self-care disabilities in higher percentages, and had higher odds ratios of having both functional disability and self-care disability compared to elderly males. The study also identified some significant factors affecting functional disability and self-care disability, namely age, having a chronic condition, wealth status and place of residence, including divisional differences. Programs aimed at reducing functional disability among seniors, particularly elderly females, should be granted the highest priority in Bangladesh.

Pervasive Transcription of a Herpesvirus Genome Generates Functionally Important RNAs

PubMed Central

Canny, Susan P.; Reese, Tiffany A.; Johnson, L. Steven; Zhang, Xin; Kambal, Amal; Duan, Erning; Liu, Catherine Y.; Virgin, Herbert W.

2014-01-01

ABSTRACT Pervasive transcription is observed in a wide range of organisms, including humans, mice, and viruses, but the functional significance of the resulting transcripts remains uncertain. Current genetic approaches are often limited by their emphasis on protein-coding open reading frames (ORFs). We previously identified extensive pervasive transcription from the murine gammaherpesvirus 68 (MHV68) genome outside known ORFs and antisense to known genes (termed expressed genomic regions [EGRs]). Similar antisense transcripts have been identified in many other herpesviruses, including Kaposi’s sarcoma-associated herpesvirus and human and murine cytomegalovirus. Despite their prevalence, whether these RNAs have any functional importance in the viral life cycle is unknown, and one interpretation is that these are merely “noise” generated by functionally unimportant transcriptional events. To determine whether pervasive transcription of a herpesvirus genome generates RNA molecules that are functionally important, we used a strand-specific functional approach to target transcripts from thirteen EGRs in MHV68. We found that targeting transcripts from six EGRs reduced viral protein expression, proving that pervasive transcription can generate functionally important RNAs. We characterized transcripts emanating from EGRs 26 and 27 in detail using several methods, including RNA sequencing, and identified several novel polyadenylated transcripts that were enriched in the nuclei of infected cells. These data provide the first evidence of the functional importance of regions of pervasive transcription emanating from MHV68 EGRs. Therefore, studies utilizing mutation of a herpesvirus genome must account for possible effects on RNAs generated by pervasive transcription. PMID:24618256

Modeling the Effects of Hydrogeomorphology and Climactic Factors on Nitrogen, Phosphorus, and Greenhouse Gas Dynamics in Riparian Zones.

NASA Astrophysics Data System (ADS)

Hassanzadeh, Y.; Vidon, P.; Gold, A.; Pradhanang, S. M.; Addy, K.

2017-12-01

Vegetated riparian zones are often considered for use as best management practices to mitigate the impacts of agriculture on water quality. However, riparian zones can also be a source of greenhouse gases and their influence on water quality varies depending on landscape hydrogeomorphic characteristics and climate. Methods used to evaluate riparian zone functions include conceptual models, and spatially explicit and process based models (REMM), but very few attempts have been made to connect riparian zone characteristics with function using easily accessible landscape scale data. Here, we present comprehensive statistical models that can be used to assess riparian zone functions with easily obtainable landscape-scale hydrogeomorphic attributes and climate data. Models were developed from a database spanning 88 years and 36 sites. Statistical methods including principal component analysis and stepwise regression were used to reduced data dimensionality and identify significant predictors. Models were validated using additional data collected from scientific literature. The 8 models developed connect landscape characteristics to nitrogen and phosphorus concentration and removal (1-4), greenhouse gas emissions (5-7), and water table depth (8). Results show the range of influence that various climate and landscape characteristics have on riparian zone functions, and the tradeoffs that exist with regards to nitrogen, phosphorous, and greenhouse gases. These models will help reduce the need for extensive field measurements and help scientists and land managers make more informed decisions regarding the use of riparian zones for water quality management.

Lovastatin inhibits T cell proliferation while preserving the cytolytic function of EBV-, CMV- and MART-1-specific CTLs

PubMed Central

Li, Dan; Li, Yufeng; Hernandez, Jessica A.; Patenia, Rebecca; Kim, Tae Kon; Khalili, Jahan; Dougherty, Mark C.; Hanley, Patrick J.; Bollard, Catherine M.; Komanduri, Krishna V.; Hwu, Patrick; Champlin, Richard E.; Radvanyi, Laszlo G.; Molldrem, Jeffrey J.; Ma, Qing

2016-01-01

Statin treatment has been shown to reduce graft-versus-host disease (GVHD) while preserving graft-versus-tumor (GVT) effect in allogeneic stem cell transplantation (allo-HCT). Herein, we investigated whether lovastatin treatment affects the function of human cytolytic T lymphocytes (CTLs). Upon TCR stimulation, lovastatin significantly inhibited the proliferation of both CD4+ and CD8+ T cells from healthy donors while their intracellular cytokine production including IFN-γ and TNF-α remained the same with a slight decrease of IL-2. Moreover, the specific lysis of target cells by CTL lines derived from patients and normal donors specific for EBV-encoded antigen LMP2 or CMV-encoded antigen pp65 was uncompromised in the presence of lovastatin. In addition, we evaluated the effect of lovastatin on the proliferation and effector function of the CD8+ tumor–infiltrating lymphocytes (TILs) derived from melanoma patients specific for MART-1 antigen. Lovastatin significantly reduced the expansion of antigen-specific TILs upon MART-1 stimulation. However, the effector function of TILs, including the specific lysis of target cells and secretion of cytokine IFN-γ, remained intact with lovastatin treatment. Taken together, these data demonstrated that lovastatin inhibits the proliferation of EBV-, CMV- and MART-1-specific CTLs without affecting cytolytic capacity. The differential effect of lovastatin on the proliferation versus cytoxicity of CTLs might shed some light on elucidating the possible mechanisms of GVHD and GVT effect elicited by alloimmune responses. PMID:20948439

Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta-Analysis

PubMed Central

Mega, Jessica L.; Simon, Tabassome; Collet, Jean-Philippe; Anderson, Jeffrey L.; Antman, Elliott M.; Bliden, Kevin; Cannon, Christopher P.; Danchin, Nicolas; Giusti, Betti; Gurbel, Paul; Horne, Benjamin D.; Hulot, Jean-Sebastian; Kastrati, Adnan; Montalescot, Gilles; Neumann, Franz-Josef; Shen, Lei; Sibbing, Dirk; Steg, P. Gabriel; Trenk, Dietmar; Wiviott, Stephen D.; Sabatine, Marc S.

2011-01-01

Content Clopidogrel, one of the most commonly prescribed medications, is a pro-drug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes. Objective In patients treated with clopidogrel, to define the risk of major adverse cardiovascular outcomes among carriers of one (∼26% prevalence in whites) and carriers of two (∼2% prevalence in whites) reduced-function CYP2C19 variants. Data Sources and Study Selection A literature search was conducted (January 2000-August 2010) of the MEDLINE, Cochrane, and EMBASE databases. Genetic studies were included where clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and where clinical outcomes were ascertained. Data Extraction Investigators from nine studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and their 95% confidence intervals (CI) for specific cardiovascular outcomes by genotype. Results Among 9685 patients [91.3% of whom underwent percutaneous coronary intervention (PCI) and 54.5% of whom had an acute coronary syndrome (ACS)], 863 experienced the composite endpoint of cardiovascular death, myocardial infarction, or stroke; 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were non-carriers, 26.3% had one, and 2.2% had two CYP2C19 reduced-function alleles. A significantly increased risk of the composite endpoint was evident in both carriers of one (HR 1.55, 95% CI 1.11-2.27, P=0.01) and two (HR 1.76, 95% CI 1.24-2.50, P=0.002) CYP2C19 reduced-function alleles. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of one (HR 2.67, 95% CI 1.69-4.22, P<0.0001) and two (HR 3.97, 95% CI 1.75-9.02, P=0.001) CYP2C19 reduced-function alleles. Conclusion Among patients treated with clopidogrel for PCI, carriage of even one reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis. PMID:20978260

Changes in Monocyte Functions of Astronauts

NASA Technical Reports Server (NTRS)

Kaur, I.; Simons, E.; Castro, V.; Ott, C. Mark; Pierson, Duane L.

2004-01-01

Monocyte cell numbers and functions, including phagocytosis, oxidative burst capacity, and degranulation and expression of related surface molecules, were studied in blood specimens from 25 astronauts and 9 healthy control subjects. Blood samples were obtained 10 days before a space flight, 3 hours after landing and 3 days after landing. The number of monocytes in astronauts did not change significantly among the three sample collection periods. Following space flight, the monocytes ability to phagocytize Escherichia coli, to exhibit an oxidative burst, and to degranulate was reduced as compared to monocytes from control subjects. These alterations in monocyte functions after space flight correlated with alterations in the expression of CD32 and CD64.

Choosing a therapy electron accelerator target.

PubMed

Hutcheon, R M; Schriber, S O; Funk, L W; Sherman, N K

1979-01-01

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.

Intertemporal consumption with directly measured welfare functions and subjective expectations

PubMed Central

Kapteyn, Arie; Kleinjans, Kristin J.; van Soest, Arthur

2010-01-01

Euler equation estimation of intertemporal consumption models requires many, often unverifiable assumptions. These include assumptions on expectations and preferences. We aim at reducing some of these requirements by using direct subjective information on respondents’ preferences and expectations. The results suggest that individually measured welfare functions and expectations have predictive power for the variation in consumption across households. Furthermore, estimates of the intertemporal elasticity of substitution based on the estimated welfare functions are plausible and of a similar order of magnitude as other estimates found in the literature. The model favored by the data only requires cross-section data for estimation. PMID:20442798

The role of business process reengineering in health care.

PubMed

Kohn, D

1994-02-01

Business process reengineering (BPR) is a management philosophy capturing attention in health care. It combines some new, old, and recycled management philosophies, and, more often than not, is yielding positive results. BPR's emphasis is on the streamlining of cross-functional processes to significantly reduce time and/or cost, increase revenue, improve quality and service, and reduce risk. Therefore, it has many applications in health care. This article provides an introduction to the concept of BPR, including the definition of BPR, its origin, its champions, and factors for its success.

Antisense and sense expression of cDNA coding for CYP73A15, a class II cinnamate 4-hydroxylase, leads to a delayed and reduced production of lignin in tobacco

NASA Technical Reports Server (NTRS)

Blee, K.; Choi, J. W.; O'Connell, A. P.; Jupe, S. C.; Schuch, W.; Lewis, N. G.; Bolwell, G. P.

2001-01-01

A number of plant species contain the class II of genes encoding the cytochrome P450, CYP73, the cognate protein of which cinnamic acid 4-hydroxylase, is the second enzyme of the phenylpropanoid pathway. In order to begin to determine possible functionality, tobacco has been transformed with a truncated French bean class II cinnamate hydroxylase (CYP73A15) in the sense and antisense orientations. Signals for C4H protein could be detected in vascular tissue from wild-type plants using heterologous probes. The transformed plants showed a normal phenotype, even though detectable C4H protein was much reduced in tissue prints. Young propagated transformants displayed a range of reduced C4H activities, as well as either reduced or no phloroglucinol-stainable lignin. However, all mature tobacco plants showed the accumulation of lignin, even though its deposition was apparently delayed. This was not due to induction of tyrosine ammonia-lyase activity, which was not detected, but instead it is presumed due to sufficient C4H residual activity. Analysis of the lignin content of the plants showed reductions of up to 30% with a slightly reduced syringyl to guaiacyl ratio as compared to wild type. This reduction level was favourable in comparison with some other targets in the lignification pathway that have been manipulated including that of class I cinnamate 4-hydroxylase. It is proposed that the class II cinnamate 4-hydroxylase might also function in lignification in a number of species including French bean and tobacco, based on these data.

Diadenosine tetraphosphate (Ap4A) inhibits ATP-induced excitotoxicity: a neuroprotective strategy for traumatic spinal cord injury treatment.

PubMed

Reigada, David; Navarro-Ruiz, Rosa María; Caballero-López, Marcos Javier; Del Águila, Ángela; Muñoz-Galdeano, Teresa; Maza, Rodrigo M; Nieto-Díaz, Manuel

2017-03-01

Reducing cell death during the secondary injury is a major priority in the development of a cure for traumatic spinal cord injury (SCI). One of the earliest processes that follow SCI is the excitotoxicity resulting from the massive release of excitotoxicity mediators, including ATP, which induce an excessive and/or prolonged activation of their receptors and a deregulation of the calcium homeostasis. Diadenosine tetraphosphate (Ap 4 A) is an endogenous purinergic agonist, present in both extracellular and intracellular fluids, with promising cytoprotective effects in different diseases including neurodegenerative processes. In a search for efficient neuroprotective strategies for SCI, we have tested the capability of Ap 4 A to reduce the excitotoxic death mediated by the ATP-induced deregulation of calcium homeostasis and its consequences on tissue preservation and functional recovery in a mouse model of moderate contusive SCI. Our analyses with the murine neural cell line Neuro2a demonstrate that treatment with Ap 4 A reduces ATP-dependent excitotoxic death by both lowering the intracellular calcium response and decreasing the expression of specific purinergic receptors. Follow-up analyses in a mouse model of contusive SCI showed that acute administration of Ap 4 A following SCI reduces tissue damage and improves motor function recovery. These results suggest that Ap 4 A cytoprotection results from a decrease of the purinergic tone preventing the effects of a massive release of ATP after SCI, probably together with a direct induction of anti-apoptotic and pro-survival pathways via activation of P2Y 2 proposed in previous studies. In conclusion, Ap 4 A may be a good candidate for an SCI therapy, particularly to reduce excitotoxicity in combination with other modulators and/or inhibitors of the excitotoxic process that are being tested.

Androgen deficiency in male patients diagnosed with ANCA-associated vasculitis: a cause of fatigue and reduced health-related quality of life?

PubMed

Tuin, Janneke; Sanders, Jan-Stephan F; Buhl, Birgit M; van Beek, André P; Stegeman, Coen A

2013-01-01

Low testosterone levels in men are associated with fatigue, limited physical performance and reduced health-related quality of life (HRQOL); however, this relationship has never been assessed in patients with anti-neutrophil cytoplasmic antibodies (ANCA) -associated vasculitides (AAV). The aim of this study was to assess the prevalence of androgen deficiency and to investigate the role of testosterone in fatigue, limited physical condition and reduced HRQOL in men with AAV. Male patients with AAV in remission were included in this study. Fatigue and HRQOL were assessed by the multi-dimensional fatigue inventory (MFI)-20 and RAND-36 questionnaires. Seventy male patients with a mean age of 59 years (SD 12) were included. Scores of almost all subscales of both questionnaires were significantly worse in patients compared to controls. Mean total testosterone and free testosterone levels were 13.8 nmol/L (SD 5.6) and 256 pmol/L (SD 102), respectively. Androgen deficiency (defined according to Endocrine Society Clinical Practice Guidelines) was present in 47% of patients. Scores in the subscales of general health perception, physical functioning and reduced activity were significantly worse in patients with androgen deficiency compared to patients with normal androgen levels. Testosterone and age were predictors for the RAND-36 physical component summary in multiple linear regression analysis. Testosterone, age, vasculitis damage index (VDI) and C-reactive protein (CRP) were associated with the MFI-20 subscale of general fatigue. This study showed that androgen deficiency was present in a substantial number of patients with AAV. Testosterone was one of the predictors for physical functioning and fatigue. Testosterone may play a role in fatigue, reduced physical performance and HRQOL in male patients with AAV.

Academic procrastination in college students: the role of self-reported executive function.

PubMed

Rabin, Laura A; Fogel, Joshua; Nutter-Upham, Katherine E

2011-03-01

Procrastination, or the intentional delay of due tasks, is a widespread phenomenon in college settings. Because procrastination can negatively impact learning, achievement, academic self-efficacy, and quality of life, research has sought to understand the factors that produce and maintain this troublesome behavior. Procrastination is increasingly viewed as involving failures in self-regulation and volition, processes commonly regarded as executive functions. The present study was the first to investigate subcomponents of self-reported executive functioning associated with academic procrastination in a demographically diverse sample of college students aged 30 years and below (n = 212). We included each of nine aspects of executive functioning in multiple regression models that also included various demographic and medical/psychiatric characteristics, estimated IQ, depression, anxiety, neuroticism, and conscientiousness. The executive function domains of initiation, plan/organize, inhibit, self-monitor, working memory, task monitor, and organization of materials were significant predictors of academic procrastination in addition to increased age and lower conscientiousness. Results enhance understanding of the neuropsychological correlates of procrastination and may lead to practical suggestions or interventions to reduce its harmful effects on students' academic performance and well-being.

Comparison of the abbreviated minimal assessment of cognitive function in multiple sclerosis (aMACFIMS) and the brief international cognitive assessment for multiple sclerosis (BICAMS).

PubMed

Gromisch, Elizabeth S; Portnoy, Jeffrey G; Foley, Frederick W

2018-05-15

Cognitive impairment is a prevalent and often intrusive problem among persons with multiple sclerosis (PwMS). Valid and reliable assessments, including quick screening measures, are crucial. The Brief International Cognitive Assessment for MS (BICAMS) was developed for this reason. While it lends itself to use in locations where formal neuropsychological resources might be limited, it does not include measures of verbal fluency or executive functioning, domains assessed as part of the Minimal Assessment of Cognitive Function in MS (MACFIMS). Given previous evidence that shortened MACFIMS measures have strong criterion validity, this study aimed to determine which of these should be included in the abbreviated MACFIMS (aMACFIMS), and how the aMACFIMS compares to the BICAMS. One hundred forty-seven PwMS were included in the analyses. A stepwise logistic regression was used to determine the measures in the aMACFIMS. Receiver-operating-characteristic (ROC) curves assessed the classification accuracy, sensitivity, and specificity. The batteries' sensitivity, specificity, and predictive values were then compared. Compared to the BICAMS, the final aMACFIMS had higher specificity (87% versus 72%) and positive predictive value (86% versus 77%), but lower sensitivity (71% versus 81%). The aMACFIMS has several benefits, including reduced administration time and the addition of a verbal fluency/executive functioning measure. Copyright © 2018 Elsevier B.V. All rights reserved.

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

PubMed

Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong

2017-12-01

Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart Association, Inc.

A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors

NASA Astrophysics Data System (ADS)

Andersson, Patrik; McGuire, Jacqueline; Rubio, Carlos; Gradin, Katarina; Whitelaw, Murray L.; Pettersson, Sven; Hanberg, Annika; Poellinger, Lorenz

2002-07-01

The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding xenobiotic metabolizing enzymes. Known receptor ligands are environmental pollutants including polycyclic aromatic hydrocarbons and polychlorinated dioxins. Loss-of-function (gene-disruption) studies in mice have demonstrated that the AhR is involved in toxic effects of dioxins but have not yielded unequivocal results concerning the physiological function of the receptor. Gain-of-function studies therefore were performed to unravel the biological functions of the AhR. A constitutively active AhR expressed in transgenic mice reduced the life span of the mice and induced tumors in the glandular part of the stomach, demonstrating the oncogenic potential of the AhR and implicating the receptor in regulation of cell proliferation.

Electronic fitness function for screening semiconductors as thermoelectric materials

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

Xing, Guangzong; Sun, Jifeng; Li, Yuwei

Here, we introduce a simple but efficient electronic fitness function (EFF) that describes the electronic aspect of the thermoelectric performance. This EFF finds materials that overcome the inverse relationship between σ and S based on the complexity of the electronic structures regardless of specific origin (e.g., isosurface corrugation, valley degeneracy, heavy-light bands mixture, valley anisotropy or reduced dimensionality). This function is well suited for application in high throughput screening. We applied this function to 75 different thermoelectric and potential thermoelectric materials including full- and half-Heuslers, binary semiconductors, and Zintl phases. We find an efficient screening using this transport function. Themore » EFF identifies known high-performance p- and n-type Zintl phases and half-Heuslers. In addition, we find some previously unstudied phases with superior EFF.« less

Prevalence of falls in elderly women

PubMed Central

Vitor, Priscila Regina Rorato; de Oliveira, Ana Carolina Kovaleski; Kohler, Renan; Winter, Gabriele Regiane; Rodacki, Cintia; Krause, Maressa Priscila

2015-01-01

OBJECTIVE: To verify prevalence of falls and fear of falling, and to compare functional fitness among elderly women fallers and non-fallers. METHODS: Seventy-eight elderly women participated in this study. Cases of falls and the fear of falling were self-reported by the elderly women, while the functional fitness was measured by a set of functional tests. Mean and standard deviation were used to describe the sample. Independent t-test was used to compare functional fitness between groups. RESULTS: The prevalence of falls in this sample was 32.4%. Among women fallers, 40% self-reported a high fear of falling. CONCLUSION: It is recommended that functional and resistance exercises are included in the preventive strategies for reducing risk factors for falls and its determinants in elderly women. Level of Evidence II, Prognostic-Prospective Study. PMID:26207095

Electronic fitness function for screening semiconductors as thermoelectric materials

DOE PAGES

Xing, Guangzong; Sun, Jifeng; Li, Yuwei; ...

2017-11-17

Here, we introduce a simple but efficient electronic fitness function (EFF) that describes the electronic aspect of the thermoelectric performance. This EFF finds materials that overcome the inverse relationship between σ and S based on the complexity of the electronic structures regardless of specific origin (e.g., isosurface corrugation, valley degeneracy, heavy-light bands mixture, valley anisotropy or reduced dimensionality). This function is well suited for application in high throughput screening. We applied this function to 75 different thermoelectric and potential thermoelectric materials including full- and half-Heuslers, binary semiconductors, and Zintl phases. We find an efficient screening using this transport function. Themore » EFF identifies known high-performance p- and n-type Zintl phases and half-Heuslers. In addition, we find some previously unstudied phases with superior EFF.« less

Human Cells Display Reduced Apoptotic Function Relative to Chimpanzee Cells

PubMed Central

McDonald, John F.

2012-01-01

Previously published gene expression analyses suggested that apoptotic function may be reduced in humans relative to chimpanzees and led to the hypothesis that this difference may contribute to the relatively larger size of the human brain and the increased propensity of humans to develop cancer. In this study, we sought to further test the hypothesis that humans maintain a reduced apoptotic function relative to chimpanzees by conducting a series of apoptotic function assays on human, chimpanzee and macaque primary fibroblastic cells. Human cells consistently displayed significantly reduced apoptotic function relative to the chimpanzee and macaque cells. These results are consistent with earlier findings indicating that apoptotic function is reduced in humans relative to chimpanzees. PMID:23029431

Meta-Transcriptomic Analysis of a Chromate-Reducing Aquifer Microbial Community

NASA Astrophysics Data System (ADS)

Beller, H. R.; Brodie, E. L.; Han, R.; Karaoz, U.

2010-12-01

A major challenge for microbial ecology that has become more tractable in the advent of new molecular techniques is characterizing gene expression in complex microbial communities. We are using meta-transcriptomic analysis to characterize functional changes in an aquifer-derived, chromate-reducing microbial community as it transitions through various electron-accepting conditions. We inoculated anaerobic microcosms with groundwater from the Cr-contaminated Hanford 100H site and supplemented them with lactate and electron acceptors present at the site, namely, nitrate, sulfate, and Fe(III). The microcosms progressed successively through various electron-accepting conditions (e.g., denitrifying, sulfate-reducing, and ferric iron-reducing conditions, as well as nitrate-dependent, chemolithotrophic Fe(II)-oxidizing conditions). Cr(VI) was rapidly reduced initially and again upon further Cr(VI) amendments. Extensive geochemical sampling and analysis (e.g., lactate, acetate, chloride, nitrate, nitrite, sulfate, dissolved Cr(VI), total Fe(II)), RNA/DNA harvesting, and PhyloChip analyses were conducted. Methods were developed for removal of rRNA from total RNA in preparation for meta-transcriptome sequencing. To date, samples representing denitrifying and fermentative/sulfate-reducing conditions have been sequenced using 454 Titanium technology. Of the non-rRNA related reads for the denitrifying sample (which was also actively reducing chromate), ca. 8% were associated with denitrification and ca. 0.9% were associated with chromate resistance/transport, in contrast to the fermentative/sulfate-reducing sample (in which chromate had already been reduced), which had zero reads associated with either of these categories but many predicted proteins associated with sulfate-reducing bacteria. We observed sequences for key functional transcripts that were unique at the nucleotide level compared to the GenBank non-redundant database [such as L-lactate dehydrogenase (iron-sulfur-cluster-binding subunit), cytochrome cd1 nitrite reductase (nirS) (from the denitrifying phase), and dissimilatory sulfite reductase (dsrA, dsrB) (from the sulfate-reducing phase)]. One potential advantage of this approach is that such important genes may not have been detected using more traditional techniques, including PCR-based methods and a priori functional microarrays.

Sexual and reproductive health in rheumatic disease.

PubMed

Østensen, Monika

2017-08-01

Family size is reduced among patients with rheumatic diseases. The causes for the low number of children are multifactorial and include impaired sexual function, decreased gonadal function, pregnancy loss, therapy and personal choices. Sexuality contributes to quality of life in patients with rheumatic disease, but is often ignored by health professionals. Both disease-related factors and psychological responses to chronic disease can impair sexual functioning. Toxic effects of anti-inflammatory and immunosuppressive drugs can induce transient or permanent gonadal failure in women and men. Furthermore, permanent infertility can be a consequence of treatment with cyclophosphamide, whereas transient infertility can be caused by NSAIDs in women and sulfasalazine in men. These adverse effects must be communicated to the patients, and measures to preserve fertility should be initiated before the start of gonadotoxic therapy. Management of patients of both genders should include regular family planning, effective treatment of high disease activity, sexual counselling, and, if necessary, infertility treatment.

Nutraceutical or Pharmacological Potential of Moringa oleifera Lam.

PubMed

Kou, Xianjuan; Li, Biao; Olayanju, Julia B; Drake, Justin M; Chen, Ning

2018-03-12

Moringa oleifera Lam. ( M. oleifera ), which belongs to the Moringaceae family, is a perennial deciduous tropical tree, and native to the south of the Himalayan Mountains in northern India. M. oleifera is rich in proteins, vitamin A, minerals, essential amino acids, antioxidants, and flavonoids, as well as isothiocyanates. The extracts from M. oleifera exhibit multiple nutraceutical or pharmacological functions including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neuroprotective, hypoglycemic, and blood lipid-reducing functions. The beneficial functions of M. oleifera are strongly associated with its phytochemicals such as flavonoids or isothiocyanates with bioactivity. In this review, we summarize the research progress related to the bioactivity and pharmacological mechanisms of M. oleifera in the prevention and treatment of a series of chronic diseases-including inflammatory diseases, neuro-dysfunctional diseases, diabetes, and cancers-which will provide a reference for its potential application in the prevention and treatment of chronic diseases or health promotion.

Thyroid hormone and cerebellar development.

PubMed

Anderson, Grant W

2008-01-01

Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

Nutraceutical or Pharmacological Potential of Moringa oleifera Lam.

PubMed Central

Kou, Xianjuan; Li, Biao; Olayanju, Julia B.; Drake, Justin M.

2018-01-01

Moringa oleifera Lam. (M. oleifera), which belongs to the Moringaceae family, is a perennial deciduous tropical tree, and native to the south of the Himalayan Mountains in northern India. M. oleifera is rich in proteins, vitamin A, minerals, essential amino acids, antioxidants, and flavonoids, as well as isothiocyanates. The extracts from M. oleifera exhibit multiple nutraceutical or pharmacological functions including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neuroprotective, hypoglycemic, and blood lipid-reducing functions. The beneficial functions of M. oleifera are strongly associated with its phytochemicals such as flavonoids or isothiocyanates with bioactivity. In this review, we summarize the research progress related to the bioactivity and pharmacological mechanisms of M. oleifera in the prevention and treatment of a series of chronic diseases—including inflammatory diseases, neuro-dysfunctional diseases, diabetes, and cancers—which will provide a reference for its potential application in the prevention and treatment of chronic diseases or health promotion. PMID:29534518

Machine-Learning Classifier for Patients with Major Depressive Disorder: Multifeature Approach Based on a High-Order Minimum Spanning Tree Functional Brain Network.

PubMed

Guo, Hao; Qin, Mengna; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

High-order functional connectivity networks are rich in time information that can reflect dynamic changes in functional connectivity between brain regions. Accordingly, such networks are widely used to classify brain diseases. However, traditional methods for processing high-order functional connectivity networks generally include the clustering method, which reduces data dimensionality. As a result, such networks cannot be effectively interpreted in the context of neurology. Additionally, due to the large scale of high-order functional connectivity networks, it can be computationally very expensive to use complex network or graph theory to calculate certain topological properties. Here, we propose a novel method of generating a high-order minimum spanning tree functional connectivity network. This method increases the neurological significance of the high-order functional connectivity network, reduces network computing consumption, and produces a network scale that is conducive to subsequent network analysis. To ensure the quality of the topological information in the network structure, we used frequent subgraph mining technology to capture the discriminative subnetworks as features and combined this with quantifiable local network features. Then we applied a multikernel learning technique to the corresponding selected features to obtain the final classification results. We evaluated our proposed method using a data set containing 38 patients with major depressive disorder and 28 healthy controls. The experimental results showed a classification accuracy of up to 97.54%.

Machine-Learning Classifier for Patients with Major Depressive Disorder: Multifeature Approach Based on a High-Order Minimum Spanning Tree Functional Brain Network

PubMed Central

Qin, Mengna; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

High-order functional connectivity networks are rich in time information that can reflect dynamic changes in functional connectivity between brain regions. Accordingly, such networks are widely used to classify brain diseases. However, traditional methods for processing high-order functional connectivity networks generally include the clustering method, which reduces data dimensionality. As a result, such networks cannot be effectively interpreted in the context of neurology. Additionally, due to the large scale of high-order functional connectivity networks, it can be computationally very expensive to use complex network or graph theory to calculate certain topological properties. Here, we propose a novel method of generating a high-order minimum spanning tree functional connectivity network. This method increases the neurological significance of the high-order functional connectivity network, reduces network computing consumption, and produces a network scale that is conducive to subsequent network analysis. To ensure the quality of the topological information in the network structure, we used frequent subgraph mining technology to capture the discriminative subnetworks as features and combined this with quantifiable local network features. Then we applied a multikernel learning technique to the corresponding selected features to obtain the final classification results. We evaluated our proposed method using a data set containing 38 patients with major depressive disorder and 28 healthy controls. The experimental results showed a classification accuracy of up to 97.54%. PMID:29387141

The interaction between NOLC1 and IAV NS1 protein promotes host cell apoptosis and reduces virus replication.

PubMed

Zhu, Chunyu; Zheng, Fangliang; Zhu, Junfeng; Liu, Meichen; Liu, Na; Li, Xue; Zhang, Li; Deng, Zaidong; Zhao, Qi; Liu, Hongsheng

2017-11-07

NS1 of the influenza virus plays an important role in the infection ability of the influenza virus. Our previous research found that NS1 protein interacts with the NOLC1 protein of host cells, however, the function of the interaction is unknown. In the present study, the role of the interaction between the two proteins in infection was further studied. Several analyses, including the use of a pull-down assay, Co-IP, western blot analysis, overexpression, RNAi, flow cytometry, etc., were used to demonstrate that the NS1 protein of H3N2 influenza virus interacts with host protein NOLC1 and reduces the quantity of NOLC1. The interaction also promotes apoptosis in A549 host cells, while the suppression of NOLC1 protein reduces the proliferation of the H3N2 virus. Based on these data, it was concluded that during the process of infection, NS1 protein interacts with NOLC1 protein, reducing the level of NOLC1, and that the interaction between the two proteins promotes apoptosis of host cells, thus reducing the proliferation of the virus. These findings provide new information on the biological function of the interaction between NS1 and NOLC1.

Symptom-reducing actions: a concept analysis in the context of chronic obstructive pulmonary disease

PubMed Central

Zakrisson, Ann-Britt

2017-01-01

ABSTRACT Patients with Chronic Obstructive Pulmonary Disease (COPD) have multiple symptoms. Nursing care is based on six core competencies and one of them is person-centred care that includes the aspect of professional symptom relief. The aim was to clarify a meaning of the concept of Symptom-reducing actions in the context of COPD. Databases MEDLINE and CINAHL were searched between 1982 and February 2016 and 26 publications were found. Two dictionaries and three books were investigated. The method of Walker & Avant was followed. The use of the concept of Symptom-reducing actions may be categorized by the sub-concepts of supervision, information, and patient education. Exploration of defining attributes was symptom management, instructions, support, motivation, explanation, advice, teaching, and learning. Antecedent occurrences were related to factors that affect the patient’s level of function such as physical performance and cognitive function. Symptom-reducing actions offer a way to support patients with COPD in self-management. Symptom-reducing actions can mediate facts in a purposeful process performed by the nurse to enable the patient to take control over and manage unpleasant symptoms by a person-centred, planned process. The nurse can achieve this via supervision, information, and patient education with an integrated emotional component. Evaluating the outcomes is needed. PMID:29034812

Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity.

PubMed

Seals, Douglas R; Justice, Jamie N; LaRocca, Thomas J

2016-04-15

Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio-economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been 'compression of morbidity' and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, 'geroscience', is focused on healthspan extension. Superimposed on this background are new attitudes and demand for 'optimal longevity' - living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio-economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

General software design for multisensor data fusion

NASA Astrophysics Data System (ADS)

Zhang, Junliang; Zhao, Yuming

1999-03-01

In this paper a general method of software design for multisensor data fusion is discussed in detail, which adopts object-oriented technology under UNIX operation system. The software for multisensor data fusion is divided into six functional modules: data collection, database management, GIS, target display and alarming data simulation etc. Furthermore, the primary function, the components and some realization methods of each modular is given. The interfaces among these functional modular relations are discussed. The data exchange among each functional modular is performed by interprocess communication IPC, including message queue, semaphore and shared memory. Thus, each functional modular is executed independently, which reduces the dependence among functional modules and helps software programing and testing. This software for multisensor data fusion is designed as hierarchical structure by the inheritance character of classes. Each functional modular is abstracted and encapsulated through class structure, which avoids software redundancy and enhances readability.

Supportive care of women with breast cancer: key concerns and practical solutions.

PubMed

Zdenkowski, Nicholas; Tesson, Stephanie; Lombard, Janine; Lovell, Melanie; Hayes, Sandra; Francis, Prudence A; Dhillon, Haryana M; Boyle, Frances M

2016-11-21

Patients diagnosed with breast cancer may have supportive care needs for many years after diagnosis. High quality multidisciplinary care can help address these needs and reduce the physical and psychological effects of breast cancer and its treatment. Ovarian suppression and extended endocrine therapy benefits are associated with vasomotor, musculoskeletal, sexual and bone density-related side effects. Aromatase inhibitor musculoskeletal syndrome is a common reason for treatment discontinuation. Treatment strategies include education, exercise, simple analgesia and a change to tamoxifen or another aromatase inhibitor. Chemotherapy-induced alopecia may be a constant reminder of breast cancer to the patient, family, friends, acquaintances and even strangers. Alopecia can be prevented in some patients using scalp-cooling technology applied at the time of chemotherapy infusion. The adverse impact of breast cancer diagnosis and treatment on sexual wellbeing is under-reported. Identification of physical and psychological impacts is needed for implementation of treatment strategies. Fear of cancer recurrence reduces quality of life and increases distress, with subsequent impact on role functioning. Identification and multidisciplinary management are key, with referral to psychosocial services recommended where indicated. The benefits of exercise include reduced fatigue, better mental health and reduced musculoskeletal symptoms, and may also include reduced incidence of breast cancer recurrence. Identification and management of unmet supportive care needs are key aspects of breast cancer care, to maximise quality of life and minimise breast cancer recurrence.

Mobilization of ventilated patients in the intensive care unit: An elicitation study using the theory of planned behavior.

PubMed

Holdsworth, Clare; Haines, Kimberley J; Francis, Jill J; Marshall, Andrea; O'Connor, Denise; Skinner, Elizabeth H

2015-12-01

Early mobilization in intensive care unit (ICU) is safe, feasible, and beneficial. However, mobilization frequently does not occur in practice. The study objective was to elicit attitudinal, normative, and control beliefs (barriers and enablers) toward the mobilization of ventilated patients, to inform development of targeted implementation interventions. A 9-item elicitation questionnaire was administered electronically to a convenience sample of multidisciplinary staff in a tertiary ICU. A snowball recruitment approach was used to target a sample size of 20 to 25. Two investigators performed word count and thematic analyses independently. Themes were cross-checked by a third investigator. Twenty-two questionnaires were completed. Respondents wrote the most text about disadvantages. Positive attitudinal beliefs included better respiratory function, reduced functional decline, and reduced muscle wasting/weakness. The main negative attitudinal beliefs were that mobilization is perceived as time consuming and poses a risk of line dislodgement/disconnection. Positive control beliefs (enablers) included increased staff availability, positive staff attitudes, engagement, and teamwork. Negative control beliefs (barriers) included unstable patient physiology and negative workplace culture. Intensive care unit staff expressed positive and negative attitudinal, normative, and control beliefs across the spectrum, and disadvantages were most frequently reported. Identified beliefs can be used to inform development of future interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Does touch massage facilitate recovery after stroke? A study protocol of a randomized controlled trial.

PubMed

Lämås, Kristina; Häger, Charlotte; Lindgren, Lenita; Wester, Per; Brulin, Christine

2016-02-04

Despite high quality stroke care, decreased sensorimotor function, anxiety and pain often remain one year after stroke which can lead to impaired health and dependence, as well as higher healthcare costs. Touch massage (TM) has been proven to decrease anxiety and pain, and improve quality of health in other conditions of reduced health, where reduced anxiety seems to be the most pronounced benefit. Thus there are reasons to believe that TM may also reduce anxiety and pain, and improve quality of life after stroke. Further, several studies indicate that somatosensory stimulation can increase sensorimotor function, and it seems feasible to believe that TM could increase independence after stroke. In this study we will evaluate effects of TM after stroke compared to sham treatment. This is a prospective randomized open-labelled control trial with blinded evaluation (PROBE-design). Fifty patients with stroke admitted to stroke units will be randomized (1:1) to either a TM intervention or a non-active transcutaneous electrical nerve stimulation (non-TENS) control group. Ten sessions of 30 min treatments (TM or control) will be administered during two weeks. Assessment of status according to the International Classification of Functioning, Disability and Health (ICF), including body function, activity, and participation. Assessment of body function will include anxiety, pain, and stress response (heart rate variability and salivary cortisol), where anxiety is the primary outcome. Activity will be assessed by means of sensorimotor function and disability, and participation by means of health-related quality of life. Assessments will be made at baseline, after one week of treatment, after two weeks of treatment, and finally a follow-up after two months. The trial has been approved by the Regional Ethical Review Board. TM seems to decrease anxiety and pain, increase health-related quality of life, and improve sensorimotor functions after stroke, but the field is largely unexplored. Considering the documented pleasant effects of massage in general, absence of reported adverse effects, and potential effects in relation to stroke, it is essential to evaluate effects of TM during the sub-acute phase after stroke. The results of this project will hopefully provide important knowledge for evidence-based care. ClinicalTrials.gov: NTC01883947.

Smart Radiation Therapy Biomaterials.

PubMed

Ngwa, Wilfred; Boateng, Francis; Kumar, Rajiv; Irvine, Darrell J; Formenti, Silvia; Ngoma, Twalib; Herskind, Carsten; Veldwijk, Marlon R; Hildenbrand, Georg Lars; Hausmann, Michael; Wenz, Frederik; Hesser, Juergen

2017-03-01

Radiation therapy (RT) is a crucial component of cancer care, used in the treatment of over 50% of cancer patients. Patients undergoing image guided RT or brachytherapy routinely have inert RT biomaterials implanted into their tumors. The single function of these RT biomaterials is to ensure geometric accuracy during treatment. Recent studies have proposed that the inert biomaterials could be upgraded to "smart" RT biomaterials, designed to do more than 1 function. Such smart biomaterials include next-generation fiducial markers, brachytherapy spacers, and balloon applicators, designed to respond to stimuli and perform additional desirable functions like controlled delivery of therapy-enhancing payloads directly into the tumor subvolume while minimizing normal tissue toxicities. More broadly, smart RT biomaterials may include functionalized nanoparticles that can be activated to boost RT efficacy. This work reviews the rationale for smart RT biomaterials, the state of the art in this emerging cross-disciplinary research area, challenges and opportunities for further research and development, and a purview of potential clinical applications. Applications covered include using smart RT biomaterials for boosting cancer therapy with minimal side effects, combining RT with immunotherapy or chemotherapy, reducing treatment time or health care costs, and other incipient applications. Copyright © 2016 Elsevier Inc. All rights reserved.

An improved push-pull voltage fed converter using a tapped output-filter inductor

NASA Technical Reports Server (NTRS)

Wester, G. W.

1983-01-01

A new concept of using a tapped output-filter inductor and an auxiliary commutating diode to reduce the likelihood of transformer core saturation in a push-pull, voltage-fed converter is presented. The linearized circuit model and transfer functions are derived with a hybrid approach using both state-space and circuit averaging. Operation of the new converter - including parasitic effects - is discussed, and a design equation for inductor tap ratio is established. It is predicted and experimentally confirmed that the new converter has more symmetrical transformer core operation, and the potential exits for lower transistor turnon current and reduced transistor voltage stress. These benefits reduce switching loss and enhance transistor reliability.

A Splice Variant of the Human Ion Channel TRPM2 Modulates Neuroblastoma Tumor Growth through Hypoxia-inducible Factor (HIF)-1/2α*

PubMed Central

Chen, Shu-jen; Hoffman, Nicholas E.; Shanmughapriya, Santhanam; Bao, Lei; Keefer, Kerry; Conrad, Kathleen; Merali, Salim; Takahashi, Yoshinori; Abraham, Thomas; Hirschler-Laszkiewicz, Iwona; Wang, JuFang; Zhang, Xue-Qian; Song, Jianliang; Barrero, Carlos; Shi, Yuguang; Kawasawa, Yuka Imamura; Bayerl, Michael; Sun, Tianyu; Barbour, Mustafa; Wang, Hong-Gang; Madesh, Muniswamy; Cheung, Joseph Y.; Miller, Barbara A.

2014-01-01

The calcium-permeable ion channel TRPM2 is highly expressed in a number of cancers. In neuroblastoma, full-length TRPM2 (TRPM2-L) protected cells from moderate oxidative stress through increased levels of forkhead box transcription factor 3a (FOXO3a) and superoxide dismutase 2. Cells expressing the dominant negative short isoform (TRPM2-S) had reduced FOXO3a and superoxide dismutase 2 levels, reduced calcium influx in response to oxidative stress, and enhanced reactive oxygen species, leading to decreased cell viability. Here, in xenografts generated with SH-SY5Y neuroblastoma cells stably expressing TRPM2 isoforms, growth of tumors expressing TRPM2-S was significantly reduced compared with tumors expressing TRPM2-L. Expression of hypoxia-inducible factor (HIF)-1/2α was significantly reduced in TRPM2-S-expressing tumor cells as was expression of target proteins regulated by HIF-1/2α including those involved in glycolysis (lactate dehydrogenase A and enolase 2), oxidant stress (FOXO3a), angiogenesis (VEGF), mitophagy and mitochondrial function (BNIP3 and NDUFA4L2), and mitochondrial electron transport chain activity (cytochrome oxidase 4.1/4.2 in complex IV). The reduction in HIF-1/2α was mediated through both significantly reduced HIF-1/2α mRNA levels and increased levels of von Hippel-Lindau E3 ligase in TRPM2-S-expressing cells. Inhibition of TRPM2-L by pretreatment with clotrimazole or expression of TRPM2-S significantly increased sensitivity of cells to doxorubicin. Reduced survival of TRPM2-S-expressing cells after doxorubicin treatment was rescued by gain of HIF-1 or -2α function. These data suggest that TRPM2 activity is important for tumor growth and for cell viability and survival following doxorubicin treatment and that interference with TRPM2-L function may be a novel approach to reduce tumor growth through modulation of HIF-1/2α, mitochondrial function, and mitophagy. PMID:25391657

Combined reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease in sedentary elders with functional limitations.

PubMed

Vaz Fragoso, Carlos A; Hsu, Fang-Chi; Brinkley, Tina; Church, Timothy; Liu, Christine K; Manini, Todd; Newman, Anne B; Stafford, Randall S; McDermott, Mary M; Gill, Thomas M

2014-09-01

Because they are potentially modifiable and may coexist, we evaluated the combined occurrence of a reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease (PAD), including its association with exertional symptoms, physical inactivity, and impaired mobility, in sedentary elders with functional limitations. Cross sectional. Lifestyle Interventions and Independence in Elder (LIFE) Study. A total of 1307 sedentary community-dwelling persons, mean age 78.9, with functional limitations (Short Physical Performance Battery [SPPB] <10). A reduced FEV1 was defined by a z-score less than -1.64 (

Drug therapies for reducing gastric acidity in people with cystic fibrosis.

PubMed

Ng, Sze May; Franchini, Angelo J

2014-07-13

Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 17 March 2014. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.

Method and system for determining precursors of health abnormalities from processing medical records

DOEpatents

None, None

2013-06-25

Medical reports are converted to document vectors in computing apparatus and sampled by applying a maximum variation sampling function including a fitness function to the document vectors to reduce a number of medical records being processed and to increase the diversity of the medical records being processed. Linguistic phrases are extracted from the medical records and converted to s-grams. A Haar wavelet function is applied to the s-grams over the preselected time interval; and the coefficient results of the Haar wavelet function are examined for patterns representing the likelihood of health abnormalities. This confirms certain s-grams as precursors of the health abnormality and a parameter can be calculated in relation to the occurrence of such a health abnormality.

Whole Grains in Amelioration of Metabolic Derangements

PubMed Central

Develaraja, Samir; Reddy, Anup; Yadav, Mukesh; Jain, Shalini; Yadav, Hariom

2017-01-01

Daily diet influences whole body metabolism, and intricately linked to the prevention or progression of metabolic diseases including obesity, diabetes and cardiovascular diseases. Several epidemiological and large scale studies have shown that diets enriched with whole grains improves metabolic function and protect from the development of metabolic diseases. Direct impact of whole grain diet can be mediated on several levels of metabolic functions i.e. reduced glycemic index, improved fat oxidation potential, increased cholesterol clearance or decreased cholesterol biosynthesis and modulation of gut microbiome. In this article we reviewed several studies indicating the beneficial effects of whole grain diets on metabolic functions, as well as discussed the potential active phytochemicals present in these whole grain foods to contribute in modulation of metabolic function in our body. PMID:28944285

The safety and effectiveness of the current treatment regimen with or without roflumilast in advanced COPD patients: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Jafari Andarian, Saeideh; Olyaeemanesh, Alireza; Hosseini, Seyed Alireza; Akbari Sari, Ali; Firoozbakhsh, Shahram; Nouhi Jadesi, Mojtaba; Mobinizadeh, Mohammadreza

2016-01-01

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease, which reduces the lung function and causes respiratory symptoms over time, and it is primarily associated with shortness of breath, cough and sputum production. Roflumilast, which is a long-acting selective inhibitor, reduces the anti-inflammatory effect of the main symptoms of COPD. The aim of this study was to compare the clinical effectiveness of adding roflumilast to the current treatment regimen of patients with severe COPD. Methods: To retrieve the marker studies, medical databases were searched up to February 2014. We included studies, which compared the clinical effectiveness and safety of roflumilast as concomitant to Long-acting ß2-agonist/Long-acting muscarinic antagonist (LABA/LAMA) regimen, in adult patients with severe COPD. The number of exacerbations, changes in the lung function FEV1, FEV1/FVC and quality of life were the major predefined outcomes. Meta-analysis of outcomes was performed by the RevMan software, with I2> 50%, representing considerable heterogeneity. Results: Seven randomized controlled trials and two systematic reviews were included. In terms of safety, participants were likely to experience more side effects from roflumilast compared to placebo, particularly gastrointestinal effects (diarrhea, nausea, vomiting), headache and weight loss. There was no significant difference in the risk of cardiac complications or flu-like symptoms or upper respiratory tract infection in the two groups. In terms of effectiveness, only a small improvement was observed in SGRQ (St George’s Respiratory Questionnaire) index. Roflumilast reduced moderate to severe attacks, and caused significant improvements in the lung function regardless of the severity of the disease and the concurrent use of other standard COPD therapies. Conclusion: Roflumilast anti-inflammatory therapy reduces the chronic bronchitis symptoms in patients with moderate to severe COPD, and it can be safely used with other drugs simultaneously. PMID:27390702

The safety and effectiveness of the current treatment regimen with or without roflumilast in advanced COPD patients: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Jafari Andarian, Saeideh; Olyaeemanesh, Alireza; Hosseini, Seyed Alireza; Akbari Sari, Ali; Firoozbakhsh, Shahram; Nouhi Jadesi, Mojtaba; Mobinizadeh, Mohammadreza

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease, which reduces the lung function and causes respiratory symptoms over time, and it is primarily associated with shortness of breath, cough and sputum production. Roflumilast, which is a long-acting selective inhibitor, reduces the anti-inflammatory effect of the main symptoms of COPD. The aim of this study was to compare the clinical effectiveness of adding roflumilast to the current treatment regimen of patients with severe COPD. To retrieve the marker studies, medical databases were searched up to February 2014. We included studies, which compared the clinical effectiveness and safety of roflumilast as concomitant to Long-acting ß2-agonist/Long-acting muscarinic antagonist (LABA/LAMA) regimen, in adult patients with severe COPD. The number of exacerbations, changes in the lung function FEV1, FEV1/FVC and quality of life were the major predefined outcomes. Meta-analysis of outcomes was performed by the RevMan software, with I(2)> 50%, representing considerable heterogeneity. Seven randomized controlled trials and two systematic reviews were included. In terms of safety, participants were likely to experience more side effects from roflumilast compared to placebo, particularly gastrointestinal effects (diarrhea, nausea, vomiting), headache and weight loss. There was no significant difference in the risk of cardiac complications or flu-like symptoms or upper respiratory tract infection in the two groups. In terms of effectiveness, only a small improvement was observed in SGRQ (St George's Respiratory Questionnaire) index. Roflumilast reduced moderate to severe attacks, and caused significant improvements in the lung function regardless of the severity of the disease and the concurrent use of other standard COPD therapies. Roflumilast anti-inflammatory therapy reduces the chronic bronchitis symptoms in patients with moderate to severe COPD, and it can be safely used with other drugs simultaneously.

The antagonistic modulation of Arp2/3 activity by N-WASP, WAVE2 and PICK1 defines dynamic changes in astrocyte morphology

PubMed Central

Murk, Kai; Blanco Suarez, Elena M.; Cockbill, Louisa M. R.; Banks, Paul; Hanley, Jonathan G.

2013-01-01

Summary Astrocytes exhibit a complex, branched morphology, allowing them to functionally interact with numerous blood vessels, neighboring glial processes and neuronal elements, including synapses. They also respond to central nervous system (CNS) injury by a process known as astrogliosis, which involves morphological changes, including cell body hypertrophy and thickening of major processes. Following severe injury, astrocytes exhibit drastically reduced morphological complexity and collectively form a glial scar. The mechanistic details behind these morphological changes are unknown. Here, we investigate the regulation of the actin-nucleating Arp2/3 complex in controlling dynamic changes in astrocyte morphology. In contrast to other cell types, Arp2/3 inhibition drives the rapid expansion of astrocyte cell bodies and major processes. This intervention results in a reduced morphological complexity of astrocytes in both dissociated culture and in brain slices. We show that this expansion requires functional myosin II downstream of ROCK and RhoA. Knockdown of the Arp2/3 subunit Arp3 or the Arp2/3 activator N-WASP by siRNA also results in cell body expansion and reduced morphological complexity, whereas depleting WAVE2 specifically reduces the branching complexity of astrocyte processes. By contrast, knockdown of the Arp2/3 inhibitor PICK1 increases astrocyte branching complexity. Furthermore, astrocyte expansion induced by ischemic conditions is delayed by PICK1 knockdown or N-WASP overexpression. Our findings identify a new morphological outcome for Arp2/3 activation in restricting rather than promoting outwards movement of the plasma membrane in astrocytes. The Arp2/3 regulators PICK1, and N-WASP and WAVE2 function antagonistically to control the complexity of astrocyte branched morphology, and this mechanism underlies the morphological changes seen in astrocytes during their response to pathological insult. PMID:23843614

Pathological Alteration in the Choroid Plexus of Alzheimer’s Disease: Implication for New Therapy Approaches

PubMed Central

Krzyzanowska, Agnieszka; Carro, Eva

2012-01-01

Morphological alterations of choroid plexus in Alzheimer’s disease (AD) have been extensively investigated. These changes include epithelial atrophy, thickening of the basement membrane, and stroma fibrosis. As a result, synthesis, secretory, and transportation functions are significantly altered resulting in decreased cerebrospinal fluid (CSF) turnover. Recent studies discuss the potential impacts of these changes, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to the amyloid peptide. Here, we review new evidences for AD-related changes in the choroid plexus. The data suggest that the significantly altered functions of the choroid plexus contribute to the multiparametric pathogenesis of late-onset AD. PMID:22563316

Polyfunctional dispersants for controlling viscosity of phyllosilicates

DOEpatents

Chaiko, David J.

2006-07-25

This invention provides phyllosilicates and polyfunctional dispersants which can be manipulated to selectively control the viscosity of phyllosilicate slurries. The polyfunctional dispersants used in the present invention, which include at least three functional groups, increase the dispersion and exfoliation of phyllosilicates in polymers and, when used in conjunction with phyllosilicate slurries, significantly reduce the viscosity of slurries having high concentrations of phyllosilicates. The functional groups of the polyfunctional dispersants are capable of associating with multivalent metal cations and low molecular weight organic polymers, which can be manipulated to substantially increase or decrease the viscosity of the slurry in a concentration dependent manner. The polyfunctional dispersants of the present invention can also impart desirable properties on the phyllosilicate dispersions including corrosion inhibition and enhanced exfoliation of the phyllosilicate platelets.

Nurse-led hypnotherapy: an innovative approach to Irritable Bowel Syndrome.

PubMed

Bremner, Helen

2013-08-01

Irritable Bowel Syndrome (IBS) is a common, chronic functional illness, which can greatly reduce patients' quality of life, and consumes healthcare resources. Standard treatments include dietary changes and medication, though these are often ineffective. Clinical studies of hypnotherapy demonstrate improvement in symptoms and quality of life in over 80% of subjects with intractable IBS. Our experience of a nurse-led hypnotherapy service for IBS in a community setting provides evidence of comparable efficacy for symptom control, improved quality of life, reduced dependence on medication and improved general health measures. We address the challenges of setting up and maintaining the service in a changing healthcare environment. This model of care could act as a template for providers of gastroenterology and functional disease services wishing to provide IBS care. Copyright © 2013 Elsevier Ltd. All rights reserved.

Calculation of the Full Scattering Amplitude without Partial Wave Decomposition II

NASA Technical Reports Server (NTRS)

Shertzer, J.; Temkin, A.

2003-01-01

As is well known, the full scattering amplitude can be expressed as an integral involving the complete scattering wave function. We have shown that the integral can be simplified and used in a practical way. Initial application to electron-hydrogen scattering without exchange was highly successful. The Schrodinger equation (SE) can be reduced to a 2d partial differential equation (pde), and was solved using the finite element method. We have now included exchange by solving the resultant SE, in the static exchange approximation. The resultant equation can be reduced to a pair of coupled pde's, to which the finite element method can still be applied. The resultant scattering amplitudes, both singlet and triplet, as a function of angle can be calculated for various energies. The results are in excellent agreement with converged partial wave results.

Generation of mice lacking DUF1220 protein domains: effects on fecundity and hyperactivity

PubMed Central

Keeney, JG; O’Bleness, MS; Anderson, N; Davis, JM; Arevalo, N; Busquet, N; Chick, W; Rozman, J; Hölter, SM; Garrett, L; Horsch, M; Beckers, J; Wurst, W; Klingenspor, M; Restrepo, D

2014-01-01

Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. In a hypothesis generating exercise, these mice were evaluated by 197 different phenotype measurements. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ2= 19.1, df = 2, p = 7.0 × 10−5). Further extensive phenotypic analyses suggest hyperactivity (p < 0.05) of DUF1220 mice and changes in gene expression levels of brain associated with distinct neurological functions and disease. Other changes that met statistical significance include an increase in plasma glucose concentration (as measured by Area Under the Curve, AUC 0-30 and AUC 30-120) in male mutants, fasting glucose levels, reduce sodium levels in male mutants, increased levels of the liver functional indicator ALAT/GPT in males, levels of alkaline phosphatase (also an indicator of liver function), mean R and SR amplitude by electrocardiography, elevated IgG3 levels, a reduced ratio of CD4:CD8 cells, and a reduced frequency of T cells; though it should be noted that many of these differences are quite small and require further examination. The linking of DUF1220 loss to a hyperactive phenotype is consistent with separate findings in which DUF1220 over expression results in a down-regulation of mitochondrial function, and potentially suggest a role in developmental metabolism. Finally, the substantially reduced fecundity we observe associated with KO mice argues that the ancestral DUF1220 domain provides an important biological function that is critical to survivability and reproductive success. PMID:25308000

Antisense apolipoprotein B therapy: where do we stand?

PubMed

Akdim, Fatima; Stroes, Erik S G; Kastelein, John J P

2007-08-01

Antisense oligonucleotides are novel therapeutic agents that reduce the number of specific mRNAs available for translation of the encoded protein. ISIS 301012 is an antisense oligonucleotide developed to reduce the hepatic synthesis of apolipoprotein B-100. Apolipoprotein B-100 is made in the liver, and antisense oligonucleotides preferentially distribute to that organ, so antisense apolipoprotein B-100 may have potential as an efficacious lipid-lowering agent. Recently, in healthy volunteers and in mild dyslipidaemic patients, this strategy as monotherapy or in conjunction with statins has shown unparalleled efficacy in reducing apolipoprotein B-100 and LDL-cholesterol. Tolerance for this novel therapy is encouraging and safety concerns currently only relate to mild injection-site reactions and rare liver-function test abnormalities. It should be noted, however, that these safety results were obtained in relatively few individuals. ISIS 301012 has initially shown promising results in experimental animal models, and in clinical trials in humans. Besides the effect of reducing apolipoprotein B-100 and LDL-cholesterol, this compound also significantly lowers plasma triglycerides. Safety concerns related to the drug include increased liver-function tests. To date no evidence of hepatic steatosis has been reported. Nonetheless, clinical trials of longer duration are required to demonstrate further safety.

An Echocardiographic Study of Left Ventricular Size and Cardiac Function in Adolescent Females with Anorexia Nervosa.

PubMed

Escudero, Carolina A; Potts, James E; Lam, Pei-Yoong; De Souza, Astrid M; Mugford, Gerald J; Sandor, George G S

2016-01-01

This retrospective case-control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls. Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and >10th percentile (AN > 10th). Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN > 10th. Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Reuseable Objects Software Environment (ROSE): Introduction to Air Force Software Reuse Workshop

NASA Technical Reports Server (NTRS)

Cottrell, William L.

1994-01-01

The Reusable Objects Software Environment (ROSE) is a common, consistent, consolidated implementation of software functionality using modern object oriented software engineering including designed-in reuse and adaptable requirements. ROSE is designed to minimize abstraction and reduce complexity. A planning model for the reverse engineering of selected objects through object oriented analysis is depicted. Dynamic and functional modeling are used to develop a system design, the object design, the language, and a database management system. The return on investment for a ROSE pilot program and timelines are charted.

Higher Blood Vitamin C Levels are Associated with Reduction of Apolipoprotein E E4-related Risks of Cognitive Decline in Women: The Nakajima Study.

PubMed

Noguchi-Shinohara, Moeko; Abe, Chiemi; Yuki-Nozaki, Sohshi; Dohmoto, Chiaki; Mori, Ayaka; Hayashi, Koji; Shibata, Syutaro; Ikeda, Yoshihisa; Sakai, Kenji; Iwasa, Kazuo; Yokogawa, Masami; Ishimiya, Mai; Nakamura, Hiroyuki; Yokoji, Hidehiro; Komai, Kiyonobu; Nakamura, Hiroyuki; Yamada, Masahito

2018-05-11

Antioxidants like vitamins C and E may minimize the risk for Alzheimer's disease. We examined whether vitamins C and E modify the apolipoprotein E (APOE) E4-related risks for developing cognitive decline. We conducted a population-based prospective study including Japanese residents aged 65 years from Nakajima, Japan. The participants received an evaluation of cognitive function and underwent blood tests including tests for vitamins C and E levels and APOE phenotypes. The APOE E4-by-gender-by-vitamin C or E interactions on developing cognitive decline were analyzed. Of 606 participants with normal cognitive function determined using a baseline survey (2007-2008), 349 completed the follow up survey between 2014 and 2016. In women with APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin C concentration tertile [multivariate OR 0.10 (95% CI 0.01-0.93)] compared with the lowest tertile. In men without APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin E concentration tertile [multivariate OR 0.19 (0.05-0.74)] as compared with the lowest tertile. Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.

Paralysis and heart failure precede ion balance disruption in heat-stressed European green crabs.

PubMed

Jørgensen, Lisa B; Overgaard, Johannes; MacMillan, Heath A

2017-08-01

Acute exposure of ectotherms to critically high temperatures causes injury and death, and this mortality has been associated with a number of physiological perturbations including impaired oxygen transport, loss of ion and water homeostasis, and neuronal failure. It is difficult to discern which of these factors, if any, is the proximate cause of heat injury because, for example, loss of ion homeostasis can impair neuromuscular function (including cardiac function), and conversely impaired oxygen transport reduces ATP supply and can thus reduce ion transport capacity. In this study we investigated if heat stress causes a loss of ion homeostasis in marine crabs and examined if such loss is related to heart failure. We held crabs (Carcinus maenas) at temperatures just below their critical thermal maximum and measured extracellular (hemolymph) and intracellular (muscle) ion concentrations over time. Analysis of Arrhenius plots for heart rates during heating ramps revealed a breakpoint temperature below which heart rate increased with temperature, and above which heart rate declined until complete cardiac failure. As hypothesised, heat stress reduced the Nernst equilibrium potentials of both K + and Na + , likely causing a depolarization of the membrane potential. To examine whether this loss of ion balance was likely to cause disruption of neuromuscular function, we exposed crabs to the same temperatures, but this time measured ion concentrations at the individual-specific times of complete paralysis (from which the crabs never recovered), and at the time of cardiac failure. Loss of ion balance was observed only after both paralysis and complete heart failure had occurred; indicating that the loss of neuromuscular function is not caused by a loss of ion homeostasis. Instead we suggest that the observed loss of ion balance may be linked to tissue damage related to heat death. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Spinal Cord Stimulation on Cardiac Sympathetic Nerve Activity in Patients with Heart Failure.

PubMed

Naar, Jan; Jaye, Deborah; Linde, Cecilia; Neužil, Petr; Doškář, Petr; Málek, Filip; Braunschweig, Frieder; Lund, Lars H; Mortensen, Lars; Linderoth, Bengt; Lind, Göran; Bone, Dianna; Scholte, Arthur J; Kueffer, Fred; Koehler, Jodi; Shahgaldi, Kambiz; Lang, Otto; Ståhlberg, Marcus

2017-05-01

Spinal cord stimulation (SCS) reduces sympathetic activity in animal models of heart failure with reduced ejection fraction (HF) but limited data exist of SCS in patients with HF. The aim of the present study was to test the primary hypothesis that SCS reduces cardiac sympathetic nerve activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-μs pulse duration, aiming at T2-T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0.46). WR was also unchanged comparing SCS-ON (41.5 ± 5.3) and SCS-OFF (39.1 ± 5.8, P = 0.30). Similarly, average New York Heart Association class (2.4 ± 0.5 vs 2.3 ± 0.6, P = 0.34), quality of life score (24 ± 16 vs 24 ± 16, P = 0.94), and left ventricular dimension and function as well as exercise capacity were all unchanged comparing SCS-ON and SCS-OFF. In patients with HF, SCS (12 hours daily, targeting the T2-T4 segments of the spinal cord) does not appear to influence cardiac sympathetic neuronal activity or function as assessed by MIBG scintigraphy. © 2017 Wiley Periodicals, Inc.

Ectodysplasin signalling deficiency in mouse models of hypohidrotic ectodermal dysplasia leads to middle ear and nasal pathology

PubMed Central

Azar, Ali; Piccinelli, Chiara; Brown, Helen; Headon, Denis; Cheeseman, Michael

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) results from mutation of the EDA, EDAR or EDARADD genes and is characterized by reduced or absent eccrine sweat glands, hair follicles and teeth, and defective formation of salivary, mammary and craniofacial glands. Mouse models with HED also carry Eda, Edar or Edaradd mutations and have defects that map to the same structures. Patients with HED have ear, nose and throat disease, but this has not been investigated in mice bearing comparable genetic mutations. We report that otitis media, rhinitis and nasopharyngitis occur at high frequency in Eda and Edar mutant mice and explore the pathogenic mechanisms related to glandular function, microbial and immune parameters in these lines. Nasopharynx auditory tube glands fail to develop in HED mutant mice and the functional implications include loss of lysozyme secretion, reduced mucociliary clearance and overgrowth of nasal commensal bacteria accompanied by neutrophil exudation. Heavy nasopharynx foreign body load and loss of gland protection alters the auditory tube gating function and the auditory tubes can become pathologically dilated. Accumulation of large foreign body particles in the bulla stimulates granuloma formation. Analysis of immune cell populations and myeloid cell function shows no evidence of overt immune deficiency in HED mutant mice. Our findings using HED mutant mice as a model for the human condition support the idea that ear and nose pathology in HED patients arises as a result of nasal and nasopharyngeal gland deficits, reduced mucociliary clearance and impaired auditory tube gating function underlies the pathological sequelae in the bulla. PMID:27378689

Characterizing Heterogeneity within Head and Neck Lesions Using Cluster Analysis of Multi-Parametric MRI Data.

PubMed

Borri, Marco; Schmidt, Maria A; Powell, Ceri; Koh, Dow-Mu; Riddell, Angela M; Partridge, Mike; Bhide, Shreerang A; Nutting, Christopher M; Harrington, Kevin J; Newbold, Katie L; Leach, Martin O

2015-01-01

To describe a methodology, based on cluster analysis, to partition multi-parametric functional imaging data into groups (or clusters) of similar functional characteristics, with the aim of characterizing functional heterogeneity within head and neck tumour volumes. To evaluate the performance of the proposed approach on a set of longitudinal MRI data, analysing the evolution of the obtained sub-sets with treatment. The cluster analysis workflow was applied to a combination of dynamic contrast-enhanced and diffusion-weighted imaging MRI data from a cohort of squamous cell carcinoma of the head and neck patients. Cumulative distributions of voxels, containing pre and post-treatment data and including both primary tumours and lymph nodes, were partitioned into k clusters (k = 2, 3 or 4). Principal component analysis and cluster validation were employed to investigate data composition and to independently determine the optimal number of clusters. The evolution of the resulting sub-regions with induction chemotherapy treatment was assessed relative to the number of clusters. The clustering algorithm was able to separate clusters which significantly reduced in voxel number following induction chemotherapy from clusters with a non-significant reduction. Partitioning with the optimal number of clusters (k = 4), determined with cluster validation, produced the best separation between reducing and non-reducing clusters. The proposed methodology was able to identify tumour sub-regions with distinct functional properties, independently separating clusters which were affected differently by treatment. This work demonstrates that unsupervised cluster analysis, with no prior knowledge of the data, can be employed to provide a multi-parametric characterization of functional heterogeneity within tumour volumes.

Longitudinal Association Between Gross Motor Capacity and Neuromusculoskeletal Function in Children and Youth With Cerebral Palsy.

PubMed

Vos, Rimke C; Becher, Jules G; Voorman, Jeanine M; Gorter, Jan Willem; van Eck, Mirjam; van Meeteren, Jetty; Smits, Dirk-Wouter; Twisk, Jos W; Dallmeijer, Annet J

2016-08-01

To examine associations over longitudinal measurements between neuromusculoskeletal function and gross motor capacity in children and youth with cerebral palsy (CP). A prospective cohort study. Rehabilitation departments of university medical centers and rehabilitations centers. A sample (N=327) consisting of 148 children (aged 5-9y) and 179 youth (aged 11-20y) with CP, Gross Motor Function Classification System level I (n=180), level II (n=44), level III (n=36), level IV (n=34), and level V (n=33). Not applicable. Gross motor capacity was assessed with the Gross Motor Function Measure-66 over a period of 2 to 4 years in different age cohorts. Neuromusculoskeletal function included selective motor control (SMC), muscle strength, spasticity, and range of motion (ROM) of the lower extremities. Multilevel analyses showed that SMC was significantly associated with gross motor capacity in children and youth with CP, showing higher values and a more favorable course of gross motor capacity in those with better SMC. Strength was only associated with gross motor capacity in youth. Reduced ROM of hip (children) and knee extension (youth) and spasticity of the hip adductors (youth) were additionally-but more weakly-associated with lower values and a less favorable course of gross motor capacity. Results indicate that children and youth with more severely impaired SMC and youth with reduced muscle strength have a less favorable course of gross motor capacity, while spasticity and reduced ROM are less determinative. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The human Nav1.5 F1486 deletion associated with long QT syndrome leads to impaired sodium channel inactivation and reduced lidocaine sensitivity

PubMed Central

Song, Weihua; Xiao, Yucheng; Chen, Hanying; Ashpole, Nicole M; Piekarz, Andrew D; Ma, Peilin; Hudmon, Andy; Cummins, Theodore R; Shou, Weinian

2012-01-01

The deletion of phenylalanine 1486 (F1486del) in the human cardiac voltage-gated sodium channel (hNav1.5) is associated with fatal long QT (LQT) syndrome. In this study we determined how F1486del impairs the functional properties of hNav1.5 and alters action potential firing in heterologous expression systems (human embryonic kidney (HEK) 293 cells) and their native cardiomyocyte background. Cells expressing hNav1.5-F1486del exhibited a loss-of-function alteration, reflected by an 80% reduction of peak current density, and several gain-of-function alterations, including reduced channel inactivation, enlarged window current, substantial augmentation of persistent late sodium current and an increase in ramp current. We also observed substantial action potential duration (APD) prolongation and prominent early afterdepolarizations (EADs) in neonatal cardiomyocytes expressing the F1486del channels, as well as in computer simulations of myocyte activity. In addition, lidocaine sensitivity was dramatically reduced, which probably contributed to the poor therapeutic outcome observed in the patient carrying the hNav1.5-F1486del mutation. Therefore, despite the significant reduction in peak current density, the F1486del mutation also leads to substantial gain-of-function alterations that are sufficient to cause APD prolongation and EADs, the predominant characteristic of LQTs. These data demonstrate that hNav1.5 mutations can have complex functional consequences and highlight the importance of identifying the specific molecular defect when evaluating potential treatments for individuals with prolonged QT intervals. PMID:22826127

Altered decorin leads to disrupted endothelial cell function: a possible mechanism in the pathogenesis of fetal growth restriction?

PubMed

Chui, A; Murthi, P; Gunatillake, T; Brennecke, S P; Ignjatovic, V; Monagle, P T; Whitelock, J M; Said, J M

2014-08-01

Fetal growth restriction (FGR) is a key cause of adverse pregnancy outcome where maternal and fetal factors are identified as contributing to this condition. Idiopathic FGR is associated with altered vascular endothelial cell functions. Decorin (DCN) has important roles in the regulation of endothelial cell functions in vascular environments. DCN expression is reduced in FGR. The objectives were to determine the functional consequences of reduced DCN in a human microvascular endothelial cell line model (HMVEC), and to determine downstream targets of DCN and their expression in primary placental microvascular endothelial cells (PLECs) from control and FGR-affected placentae. Short-interference RNA was used to reduce DCN expression in HMVECs and the effect on proliferation, angiogenesis and thrombin generation was determined. A Growth Factor PCR Array was used to identify downstream targets of DCN. The expression of target genes in control and FGR PLECs was performed. DCN reduction decreased proliferation and angiogenesis but increased thrombin generation with no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18 and MSTN. Validation of target genes confirmed decreased expression of VEGFA, MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies. Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coenzyme Q supplementation in pulmonary arterial hypertension

PubMed Central

Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

2014-01-01

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

Waterway Equipment - Boat, Barge, Motor

DTIC Science & Technology

2012-09-25

identification and condition (new or used). b. Pretest cleaning performed, if any. c. Species of fungus grown and inoculated on the cotton control... Pretest functional check results. c. Pretest visual inspection results. d. Posttest visual inspection results. e. Repairs or maintenance...information, including suggestions for reducing this burden, to Department of Defense, Washington Headquarters Services, Directorate for information on

Language Laterality in Autism Spectrum Disorder and Typical Controls: A Functional, Volumetric, and Diffusion Tensor MRI Study

ERIC Educational Resources Information Center

Knaus, Tracey A.; Silver, Andrew M.; Kennedy, Meaghan; Lindgren, Kristen A.; Dominick, Kelli C.; Siegel, Jeremy; Tager-Flusberg, Helen

2010-01-01

Language and communication deficits are among the core features of autism spectrum disorder (ASD). Reduced or reversed asymmetry of language has been found in a number of disorders, including ASD. Studies of healthy adults have found an association between language laterality and anatomical measures but this has not been systematically…

Expression profiling of ascorbic acid-related genes during tomato fruit development and ripening and in response to stress conditions

USDA-ARS?s Scientific Manuscript database

L-Ascorbate (the reduced form of Vitamin C) participates in diverse biological processes including pathogen defense mechanisms, the modulation of plant growth and morphology and also acts as an enzyme cofactor, and redox status indicator. One of its chief biological functions is as an antioxidant. L...

Postural Strategies in Prader-Willi and Down Syndrome Patients

ERIC Educational Resources Information Center

Cimolin, Veronica; Galli, Manuela; Grugni, Graziano; Vismara, Luca; Precilios, Helmer; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

Patients affected by Down (DS) and Prader-Willi syndrome (PWS) are characterised by some common clinical and functional features including gait disorders and reduced postural control. The aim of our study was to quantitatively compare postural control in adult PWS and DS. We studied 12 PWS and 19 DS adult patients matched for age, height, weight…

DOPA Decarboxylase Modulates Tau Toxicity.

PubMed

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

Male fertility potential alteration in rheumatic diseases: a systematic review

PubMed Central

Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfá, Eloisa; Srougi, Miguel; Clovis, A

2016-01-01

ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy. PMID:27120778

Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.

PubMed

Booker, Sam A; Campbell, Graham R; Mysiak, Karolina S; Brophy, Peter J; Kind, Peter C; Mahad, Don J; Wyllie, David J A

2017-03-15

Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity. Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission. High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice. Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function. Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses with CA3 pyramidal cells via large mossy-fibre boutons, but rather to all synapses formed by dentate granule cells. Therefore, presynaptic mitochondrial function is critical for the short-term dynamics of synapse function, which may contribute to the cognitive deficits observed in pathological mitochondrial dysfunction. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Dysfunctional, but not functional, impulsivity is associated with a history of seriously violent behaviour and reduced orbitofrontal and hippocampal volumes in schizophrenia.

PubMed

Kumari, Veena; Barkataki, Ian; Goswami, Sangeeta; Flora, Satinder; Das, Mrigendra; Taylor, Pamela

2009-07-15

Aggression and violent acts have been linked with impulsive responding. We investigated whether impulsive personality trait, especially suggestive of dysfunctional impulsivity (i.e. fast and inaccurate responding where this is non-optimal), is associated with a history of seriously violent behaviour and specific brain deficits in schizophrenia. Twenty-four male participants with schizophrenia, of whom 10 had a history of serious physical violence, and 14 healthy male participants were assessed on impulsiveness (dysfunctional impulsivity), venturesomeness (functional impulsivity), and empathy. All participants underwent magnetic resonance imaging. The results revealed that participants with schizophrenia and a history of violence showed elevated impulsiveness but had comparable scores on venturesomeness and empathy dimensions. Impulsiveness scores correlated negatively with reduced orbitofrontal grey matter volume in both the patient and healthy control groups, and with hippocampal volume in the patient group. Our findings suggest that dysfunctional, but not functional, impulsivity is elevated in patients with schizophrenia with a propensity for repetitive violence, and this in turn appears to be associated with reduce volumes of both the orbitofrontal cortex grey matter and the hippocampus. Violence risk prediction and management strategies in schizophrenia may benefit from including specific measures of dysfunctional impulsive traits.

Effects of Swimming and Cycling Exercise Intervention on Vascular Function in Patients With Osteoarthritis.

PubMed

Alkatan, Mohammed; Machin, Daniel R; Baker, Jeffrey R; Akkari, Amanda S; Park, Wonil; Tanaka, Hirofumi

2016-01-01

Swimming exercise is an ideal and excellent form of exercise for patients with osteoarthritis (OA). However, there is no scientific evidence that regular swimming reduces vascular dysfunction and inflammation and elicits similar benefits compared with land-based exercises such as cycling in terms of reducing vascular dysfunction and inflammation in patients with OA. Forty-eight middle-aged and older patients with OA were randomly assigned to swimming or cycling training groups. Cycling training was included as a non-weight-bearing land-based comparison group. After 12 weeks of supervised exercise training, central arterial stiffness, as determined by carotid-femoral pulse wave velocity, and carotid artery stiffness, through simultaneous ultrasound and applanation tonometry, decreased significantly after both swimming and cycling training. Vascular endothelial function, as determined by brachial flow-mediated dilation, increased significantly after swimming but not after cycling training. Both swimming and cycling interventions reduced interleukin-6 levels, whereas no changes were observed in other inflammatory markers. In conclusion, these results indicate that regular swimming exercise can exert similar or even superior effects on vascular function and inflammatory markers compared with land-based cycling exercise in patients with OA who often has an increased risk of developing cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Ballew, Shoshana H.; Chen, Yan; Daya, Natalie R.; Godino, Job G.; Windham, B. Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E.

2016-01-01

Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011–2013). Predictor Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) and urine albumin-creatinine ratio (ACR). Outcomes Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results In total, 341 participants (7%) were classified as frail, 1475 (30%) had eGFRcr <60 ml/min/1.73 m2, 2480 (50%) had eGFRcys <60 ml/min/1.73 m2, and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60 ml/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and ACR. Frail individuals with eGFRcr 60–<75 ml/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of non-frail), including classes requiring kidney clearance (e.g., digoxin) and associated with falls and subsequent complications (e.g., hypnotic/sedatives, anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduce kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in CKD classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population. PMID:27884475

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle

PubMed Central

Muir, Lindsey A.; Murry, Charles E.

2016-01-01

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a KATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle. PMID:27503462

Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy.

PubMed

Mercuri, Eugenio; Signorovitch, James Edward; Swallow, Elyse; Song, Jinlin; Ward, Susan J

2016-09-01

High variability in patients' changes in 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy in Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory boys aged 5 years or older with genetically confirmed DMD who were enrolled in a natural history study at 11 care centers throughout Italy were included. For each boy, standardized assessments of 6MWD were available at annual intervals spanning 3 years. Trajectories of 6MWD vs. age and trajectories of 6MWD vs. time from enrollment were examined using latent class analysis. A total of 96 boys were included. At enrollment, the mean age was 8.3 years (mean 6MWD: 374 meters). After accounting for age, baseline 6MWD, and steroid use, four latent trajectory classes were identified as explaining 3-year 6MWD outcomes significantly better than a single average trajectory. Patient trajectories of 6MWD change from enrollment were categorized as having fast decline (n = 25), moderate decline (n = 19), stable function (n = 37), and improving function (n = 15) during the 3-year follow-up. After accounting for trajectory classes, the standard deviation of variation in 6MWD was reduced by approximately 40%. The natural history of ambulatory function in DMD may be composed of distinct trajectory classes. The extent to which trajectories are associated with novel and established prognostic factors warrants further study. Reducing unexplained variation in patient outcomes could help to further improve DMD clinical trial design and analysis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Surgical Versus Conservative Intervention for Acute Achilles Tendon Rupture: A PRISMA-Compliant Systematic Review of Overlapping Meta-Analyses.

PubMed

Zhang, Hao; Tang, Hao; He, Qianyun; Wei, Qiang; Tong, Dake; Wang, Chuangfeng; Wu, Dajiang; Wang, Guangchao; Zhang, Xin; Ding, Wenbin; Li, Di; Ding, Chen; Liu, Kang; Ji, Fang

2015-11-01

Although many meta-analyses comparing surgical intervention with conservative treatment have been conducted for acute Achilles tendon rupture, discordant conclusions are shown. This study systematically reviewed the overlapping meta-analyses relating to surgical versus conservative intervention of acute Achilles tendon rupture to assist decision makers select among conflicting meta-analyses, and to offer intervention recommendations based on the currently best evidence.Multiple databases were comprehensively searched for meta-analyses comparing surgical with conservative treatment of acute Achilles tendon rupture. Meta-analyses only comprising randomized controlled trials (RCTs) were included. Two authors independently evaluated the meta-analysis quality and extracted data. The Jadad decision algorithm was applied to ascertain which meta-analysis offered the best evidence.A total of 9 meta-analyses were included. Only RCTs were determined as Level-II evidence. The scores of Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 5 to 10 (median 7). A high-quality meta-analysis with more RCTs was selected according to the Jadad decision algorithm. This study found that when functional rehabilitation was used, conservative intervention was equal to surgical treatment regarding the incidence of rerupture, range of motion, calf circumference, and functional outcomes, while reducing the incidence of other complications. Where functional rehabilitation was not performed, conservative intervention could significantly increase rerupture rate.Conservative intervention may be preferred for acute Achilles tendon rupture at centers offering functional rehabilitation, because it shows a similar rerupture rate with a lower risk of other complications when compared with surgical treatment. However, surgical treatment should be considered at centers without functional rehabilitation as this can reduce the incidence of rerupture.

Prosurvival Factors Improve Functional Engraftment of Myogenically Converted Dermal Cells into Dystrophic Skeletal Muscle.

PubMed

Muir, Lindsey A; Murry, Charles E; Chamberlain, Jeffrey S

2016-09-07

In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell therapies are a promising route for promoting muscle regeneration by supplying a functional copy of the missing dystrophin gene and contributing new muscle fibers. The clinical application of cell-based therapies is resource intensive, and it will therefore be necessary to address key limitations that reduce cell engraftment into muscle tissue. A pressing issue is poor donor cell survival following transplantation, which in preclinical studies limits the ability to effectively test the impact of cell-based therapy on whole muscle function. We, therefore, sought to improve engraftment and the functional impact of in vivo myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail (PSC) that includes heat shock followed by treatment with insulin-like growth factor-1, a caspase inhibitor, a Bcl-XL peptide, a K ATP channel opener, basic fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs include compatibility with the autologous setting, ease of isolation, and greater proliferative potential than DMD satellite cells. dFbs expressed tamoxifen-inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific promoter. After transplantation into muscles of mdx mice, a 70% reduction in donor cells was observed by day 5, and a 94% reduction by day 28. However, treatment with PSC gave a nearly three-fold increase in donor cells in early engraftment, and greatly increased the number of donor-contributed muscle fibers and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles that received dFbs with PSC displayed reduced injury with eccentric contractions and an increase in maximum isometric force. Thus, enhancing survival of myogenic cells increases engraftment and improves structure and function of dystrophic muscle.

Assessment and management of respiratory function in patients with Duchenne muscular dystrophy: current and emerging options

PubMed Central

LoMauro, Antonella; D’Angelo, Maria Grazia; Aliverti, Andrea

2015-01-01

Duchenne muscular dystrophy (DMD) is an X-linked myopathy resulting in progressive weakness and wasting of all the striated muscles including the respiratory muscles. The consequences are loss of ambulation before teen ages, cardiac involvement and breathing difficulties, the main cause of death. A cure for DMD is not currently available. In the last decades the survival of patients with DMD has improved because the natural history of the disease can be changed thanks to a more comprehensive therapeutic approach. This comprises interventions targeted to the manifestations and complications of the disease, particularly in the respiratory care. These include: 1) pharmacological intervention, namely corticosteroids and idebenone that significantly reduce the decline of spirometric parameters; 2) rehabilitative intervention, namely lung volume recruitment techniques that help prevent atelectasis and slows the rate of decline of pulmonary function; 3) scoliosis treatment, namely steroid therapy that is used to reduce muscle inflammation/degeneration and prolong ambulation in order to delay the onset of scoliosis, being an additional contribution to the restrictive lung pattern; 4) cough assisted devices that improve airway clearance thus reducing the risk of pulmonary infections; and 5) non-invasive mechanical ventilation that is essential to treat nocturnal hypoventilation, sleep disordered breathing, and ultimately respiratory failure. Without any intervention death occurs within the first 2 decades, however, thanks to this multidisciplinary therapeutic approach life expectancy of a newborn with DMD nowadays can be significantly prolonged up to his fourth decade. This review is aimed at providing state-of-the-art methods and techniques for the assessment and management of respiratory function in DMD patients. PMID:26451113

Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder

PubMed Central

Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

2016-01-01

Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients. PMID:27271861

Lipid Lowering with Soluble Dietary Fiber.

PubMed

Surampudi, Prasanth; Enkhmaa, Byambaa; Anuurad, Erdembileg; Berglund, Lars

2016-12-01

Consumption of dietary soluble fibers has been associated with health benefits such as reduced lipid levels, lower blood pressure, improved blood glucose control, weight loss, improved immune function, and reduced inflammation. Many of these health benefits relate to a reduced risk of developing cardiovascular disease. In this paper, we have reviewed recent studies on the hypocholesterolemic effects of dietary soluble fibers as well as fiber-rich foods. Findings include the following: (a) consumption of water-soluble, viscous-forming fibers can reduce total and low-density lipoprotein cholesterol levels by about 5-10 %; (b) minimal changes of high-density lipoprotein cholesterol or triglyceride levels were observed; (c) cholesterol-lowering properties of soluble fibers depend on their physical and chemical properties; and (d) medium to high molecular weight fibers are more effective in reducing lipid levels. Hypocholesterolemic benefits were also observed with some fiber-rich foods, such as whole oats, whole barley, legumes, peas, beans, flax seeds, apples, and citrus foods.

Including Effects of Water Stress on Dead Organic Matter Decay to a Forest Carbon Model

NASA Astrophysics Data System (ADS)

Kim, H.; Lee, J.; Han, S. H.; Kim, S.; Son, Y.

2017-12-01

Decay of dead organic matter is a key process of carbon (C) cycling in forest ecosystems. The change in decay rate depends on temperature sensitivity and moisture conditions. The Forest Biomass and Dead organic matter Carbon (FBDC) model includes a decay sub-model considering temperature sensitivity, yet does not consider moisture conditions as drivers of the decay rate change. This study aimed to improve the FBDC model by including a water stress function to the decay sub-model. Also, soil C sequestration under climate change with the FBDC model including the water stress function was simulated. The water stress functions were determined with data from decomposition study on Quercus variabilis forests and Pinus densiflora forests of Korea, and adjustment parameters of the functions were determined for both species. The water stress functions were based on the ratio of precipitation to potential evapotranspiration. Including the water stress function increased the explained variances of the decay rate by 19% for the Q. variabilis forests and 7% for the P. densiflora forests, respectively. The increase of the explained variances resulted from large difference in temperature range and precipitation range across the decomposition study plots. During the period of experiment, the mean annual temperature range was less than 3°C, while the annual precipitation ranged from 720mm to 1466mm. Application of the water stress functions to the FBDC model constrained increasing trend of temperature sensitivity under climate change, and thus increased the model-estimated soil C sequestration (Mg C ha-1) by 6.6 for the Q. variabilis forests and by 3.1 for the P. densiflora forests, respectively. The addition of water stress functions increased reliability of the decay rate estimation and could contribute to reducing the bias in estimating soil C sequestration under varying moisture condition. Acknowledgement: This study was supported by Korea Forest Service (2017044B10-1719-BB01)

Diabetic Neuropathy: Mechanisms, Emerging Treatments, and Subtypes

PubMed Central

Pop-Busui, Rodica

2016-01-01

Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na+/K+-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality. PMID:24954624

Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity

PubMed Central

Justice, Jamie N.; LaRocca, Thomas J.

2015-01-01

Abstract Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio‐economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been ‘compression of morbidity’ and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, ‘geroscience’, is focused on healthspan extension. Superimposed on this background are new attitudes and demand for ‘optimal longevity’ – living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first‐line function‐preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel ‘nutraceutical’ compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio‐economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health. PMID:25639909

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

PubMed Central

Veit, Guido; Avramescu, Radu G.; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M.; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E.; Hegedus, Tamas; Verkman, Alan S.; Lukacs, Gergely L.

2015-01-01

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770–induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)–NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. PMID:25101887

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

PubMed

Veit, Guido; Avramescu, Radu G; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E; Hegedus, Tamas; Verkman, Alan S; Lukacs, Gergely L

2014-07-23

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. Copyright © 2014, American Association for the Advancement of Science.

Depressive symptoms are associated with reduced neutrophil function in hip fracture patients☆

PubMed Central

Duggal, Niharika Arora; Upton, Jane; Phillips, Anna C.; Hampson, Peter; Lord, Janet M.

2013-01-01

Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p = .001) or controls (p = .004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels. PMID:23876747

Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat.

PubMed

Bakrania, B; Du Toit, E F; Ashton, K J; Wagner, K-H; Headrick, J P; Bulmer, A C

2017-08-01

Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content. No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin in vivo. Ex vivo analysis of baseline function revealed reduced left ventricular pressure development (LVDP) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post-ischaemic recoveries of LVDP (76 ± 22% vs. 29 ± 17% Control, P < 0.01) and coronary flow (96 ± 9% vs. 86 ± 16% Control, P < 0.01) were improved in Gunn hearts, accompanied by reduced infarct area (21 ± 5% vs. 47 ± 15% Control, P < 0.01), and ventricular malondialdehyde and protein carbonyl content. Expression of myocardial nitric oxide-regulating genes including Nos1 and Noa1 were not significantly different. These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resistance. In addition, bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Preparation of lactic acid bacteria fermented wheat-yoghurt mixtures.

PubMed

Magala, Michal; Kohajdová, Zlatica; Karovičová, Jolana

2013-01-01

Tarhana, a wheat-yoghurt fermented mixture, is considered as a good source of saccharides, proteins, some vitamins and minerals. Moreover, their preparation is inexpensive and lactic acid fermentation offers benefits like product preservation, enhancement of nutritive value and sensory properties improvement. The aim of this work was to evaluate changes of some chemical parameters during fermentation of tarhana, when the level of salt and amount of yoghurt used were varied. Some functional and sensory characteristics of the fi nal product were also determined. Chemical analysis included determination of pH, titrable acidity, content of reducing saccharides, lactic, acetic and citric acid. Measured functional properties of tarhana powder were foaming capacity, foam stability, water absorption capacity, oil absorption capacity and emulsifying activity. Tarhana soups samples were evaluated for their sensory characteristics (colour, odor, taste, consistency and overall acceptability). Fermentation of tarhana by lactic acid bacteria and yeasts led to decrease in pH, content of reducing saccharides and citric acid, while titrable acidity and concentration of lactic and acetic acid increased. Determination of functional properties of tarhana powder showed, that salt absence and increased amount of yoghurt in tarhana recipe reduced foaming capacity and oil absorption capacity, whereas foam stability and water absorption capacity were improved. Sensory evaluation of tarhana soups showed that variations in tarhana recipe adversly affected sensory parameters of fi nal products. Variations in tarhana recipe (salt absence, increased proportion of yoghurt) led to changes in some chemical parameters (pH, titrable acidity, reducing saccharides, content of lactic, acetic and citric acid). Functional properties were also affected with changed tarhana recipe. Sensory characteristics determination showed, that standard tarhana fermented for 144 h had the highest overall acceptability.

Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

PubMed

Pratschke, Sebastian; Rauch, Alexandra; Albertsmeier, Markus; Rentsch, Markus; Kirschneck, Michaela; Andrassy, Joachim; Thomas, Michael; Hartwig, Werner; Figueras, Joan; Del Rio Martin, Juan; De Ruvo, Nicola; Werner, Jens; Guba, Markus; Weniger, Maximilian; Angele, Martin K

2016-12-01

The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2 ) were also utilized. Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

Functional structure of the bromeliad tank microbiome is strongly shaped by local geochemical conditions.

PubMed

Louca, Stilianos; Jacques, Saulo M S; Pires, Aliny P F; Leal, Juliana S; González, Angélica L; Doebeli, Michael; Farjalla, Vinicius F

2017-08-01

Phytotelmata in tank-forming Bromeliaceae plants are regarded as potential miniature models for aquatic ecology, but detailed investigations of their microbial communities are rare. Hence, the biogeochemistry in bromeliad tanks remains poorly understood. Here we investigate the structure of bacterial and archaeal communities inhabiting the detritus within the tanks of two bromeliad species, Aechmea nudicaulis and Neoregelia cruenta, from a Brazilian sand dune forest. We used metagenomic sequencing for functional community profiling and 16S sequencing for taxonomic profiling. We estimated the correlation between functional groups and various environmental variables, and compared communities between bromeliad species. In all bromeliads, microbial communities spanned a metabolic network adapted to oxygen-limited conditions, including all denitrification steps, ammonification, sulfate respiration, methanogenesis, reductive acetogenesis and anoxygenic phototrophy. Overall, CO2 reducers dominated in abundance over sulfate reducers, and anoxygenic phototrophs largely outnumbered oxygenic photoautotrophs. Functional community structure correlated strongly with environmental variables, between and within a single bromeliad species. Methanogens and reductive acetogens correlated with detrital volume and canopy coverage, and exhibited higher relative abundances in N. cruenta. A comparison of bromeliads to freshwater lake sediments and soil from around the world, revealed stark differences in terms of taxonomic as well as functional microbial community structure. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress.

PubMed

Kassan, M; Vikram, A; Kim, Y R; Li, Q; Kassan, A; Patel, H H; Kumar, S; Gabani, M; Liu, J; Jacobs, J S; Irani, K

2017-02-09

Sirtuin1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including endothelial function. Caveolin1 (Cav1) is also an important determinant of endothelial function. We asked if Sirt1 governs endothelial Cav1 and endothelial function by regulating miR-204 expression and endoplasmic reticulum (ER) stress. Knockdown of Sirt1 in endothelial cells, and in vivo deletion of endothelial Sirt1, induced endothelial ER stress and miR-204 expression, reduced Cav1, and impaired endothelium-dependent vasorelaxation. All of these effects were reversed by a miR-204 inhibitor (miR-204 I) or with overexpression of Cav1. A miR-204 mimic (miR-204 M) decreased Cav1 in endothelial cells. In addition, high-fat diet (HFD) feeding induced vascular miR-204 and reduced endothelial Cav1. MiR-204-I protected against HFD-induced downregulation of endothelial Cav1. Moreover, pharmacologic induction of ER stress with tunicamycin downregulated endothelial Cav1 and impaired endothelium-dependent vasorelaxation that was rescued by overexpressing Cav1. In conclusion, Sirt1 preserves Cav1-dependent endothelial function by mitigating miR-204-mediated vascular ER stress.

Orbit-determination performance of Doppler data for interplanetary cruise trajectories. Part 2: 8.4-GHz performance and data-weighting strategies

NASA Technical Reports Server (NTRS)

Ulvestad, J. S.

1992-01-01

A consider error covariance analysis was performed in order to investigate the orbit-determination performance attainable using two-way (coherent) 8.4-GHz (X-band) Doppler data for two segments of the planned Mars Observer trajectory. The analysis includes the effects of the current level of calibration errors in tropospheric delay, ionospheric delay, and station locations, with particular emphasis placed on assessing the performance of several candidate elevation-dependent data-weighting functions. One weighting function was found that yields good performance for a variety of tracking geometries. This weighting function is simple and robust; it reduces the danger of error that might exist if an analyst had to select one of several different weighting functions that are highly sensitive to the exact choice of parameters and to the tracking geometry. Orbit-determination accuracy improvements that may be obtained through the use of calibration data derived from Global Positioning System (GPS) satellites also were investigated, and can be as much as a factor of three in some components of the spacecraft state vector. Assuming that both station-location errors and troposphere calibration errors are reduced simultaneously, the recommended data-weighting function need not be changed when GPS calibrations are incorporated in the orbit-determination process.

The results of a wind tunnel investigation of a model rotor with a free tip

NASA Technical Reports Server (NTRS)

Stroub, Robert H.; Young, Larry A.

1985-01-01

The results of a wind-tunnel test of the free tip rotor are presented. The free tip extended over the outer 10% of the rotor blade and included a simple, passive controller mechanism. Wind-tunnel test hardware is described. The free-tip assembly, which includes the controller, functioned flawlessly throughout the test. The tip pitched freely and responded to airflow perturbation in a sharp, quick, and stable manner. Tip pitch-angle responses are presented for an advance ratio range of 0.1 to 0.397 and for a thrust coefficient range of 0.038 to 0.092. The free tip reduced power requirements, loads going into the control system, and some flatwise blade-bending moments. Chordwise loads were not reduced by the free tip.

Cinetica de oxidacion de polimeros conductores: poli-3,4- etilendioxitiofeno

NASA Astrophysics Data System (ADS)

Caballero Romero, Maria

Films of poly-3,4-ethylenedioxythiophene (PEDOT) perchlorate used as electrodes in liquid electrolytes incorporate anions and solvent during oxidation for charge and osmotic balance: the film swells. During reduction the film shrinks, closes its structure trapping counterions getting then rising conformational packed states by expulsion of counterions and solvent. Here by potential step from the same reduced initial state to the same oxidized final state the rate coefficient, the activation energy and reaction orders related to the counterion concentration in solution and to the concentration of active centers in the polymer film, were attained following the usual methodology used for chemical and electrochemical kinetics. Now the full methodology was repeated using different reduced-shrunk or reduced-conformational compacted initial states every time. Those initial states were attained by reduction of the oxidized film at rising cathodic potentials for the same reduction time each. Rising reduced and conformational compacted states give slower subsequent oxidation rates by potential step to the same anodic potential every time. The activation energy, the reaction coefficient and reaction orders change for rising conformational compacted initial states. Decreasing rate constants and increasing activation energies are obtained for the PEDOT oxidation from increasing conformational compacted initial states. The experimental activation energy presents two linear ranges as a function of the initial reduced-compacted state. Using as initial states for the oxidation open structures attained by reduction at low cathodic potentials, activation energies attained were constant: namely the chemical activation energy. Using as initial states for the oxidation deeper reduced, closed and packed conformational structures, the activation energy includes two components: the constant chemical energy plus the conformational energy required to relax the conformational structure generating free volume which allows the entrance of the balancing counterions required for the reaction. The conformational energy increases linearly as a function of the reduction-compaction potential. The kinetic magnitudes include conformational and structural information. The Chemical Kinetics becomes Structural (or conformational) Chemical Kinetics.

[Soft tissue sarcoma of the upper extremities. Analysis of factors relevant for prognosis in 160 patients].

PubMed

Lehnhardt, M; Hirche, C; Daigeler, A; Goertz, O; Ring, A; Hirsch, T; Drücke, D; Hauser, J; Steinau, H U

2012-02-01

Soft tissue sarcomas (STS) are a rare entity with reduced prognosis due to their aggressive biology. For an optimal treatment of STS identification of independent prognostic factors is crucial in order to reduce tumor-related mortality and recurrence rates. The surgical oncological concept includes wide excisions with resection safety margins >1 cm which enables acceptable functional results and reduced rates of amputation of the lower extremities. In contrast, individual anatomy of the upper extremities, in particular of the hand, leads to an intentional reduction of resection margins in order to preserve the extremity and its function with the main intention of tumor-free resection margins. In this study, the oncological safety and outcome as well as functional results were validated by a retrospective analysis of survival rate, recurrence rate and potential prognostic factors. A total of 160 patients who had been treated for STS of the upper extremities were retrospectively included. Independent prognostic factors were analyzed (primary versus recurrent tumor, tumor size, resection status, grade of malignancy, additional therapy, localization in the upper extremity). Kaplan-Meier analyses for survival rate and local control were calculated. Further outcome measures were functional results validated by the DASH score and rate of amputation. In 130 patients (81%) wide tumor excision (R0) was performed and in 19 patients (12%) an amputation was necessary. The 5-year overall survival rate was 70% and the 5-year survival rate in primary tumors was 81% whereas in recurrences 55% relapsed locally. The 10-year overall survival rate was 45% and the 5-year recurrence rate was 18% for primary STS and 43% for recurrent STS. Variance analysis revealed primary versus recurrent tumor, tumor size, resection status and grade of malignancy as independent prognostic factors. Analysis of functional results showed a median DASH score of 37 (0-100; 0=contralateral extremity). The 5-year survival and local recurrence rates are comparable to STS wide resections with safety margins >1 cm for the lower extremities and the trunk. Analysis of prognostic factors revealed resection status and the tumor-free resection margins to be the main goals in STS resection of upper extremity.

Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity.

PubMed

Li, Wei; Tang, Renqiao; Ouyang, Shengrong; Ma, Feifei; Liu, Zhuo; Wu, Jianxin

2017-01-01

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

Relationship between family quality of life and day occupations of young people with Down syndrome.

PubMed

Foley, Kitty-Rose; Girdler, Sonya; Downs, Jenny; Jacoby, Peter; Bourke, Jenny; Lennox, Nick; Einfeld, Stewart; Llewellyn, Gwynnyth; Parmenter, Trevor R; Leonard, Helen

2014-09-01

To explore relationships between family quality of life, day occupations and activities of daily living (ADL) of young persons with Down syndrome. Data were collected from 150 families with a young person with Down syndrome aged 16-30 years participating in the Down syndrome "Needs Opinions Wishes" database. Data described the young person's characteristics (including functional abilities, behaviour and day occupations) and family characteristics (including income, family and community supports and quality of life). Compared to families of young people attending open employment, families of young people participating in sheltered employment tended to report poorer family quality of life, after adjusting for personal characteristics, behaviour and income (coeff -6.78, 95 % CI -14.38, 0.81). Family supports reduced this relationship (coeff -6.00, 95 % CI -12.76, 0.76). Families of young people with greater functioning in ADL reported better family quality of life regardless of personal and environmental factors (coeff 0.45, 95 % CI 0.05, 0.85) and inclusion of family factors such as family supports reduced this association (coeff 0.29, 95 % CI -0.10, 0.67). Participation of young people with Down syndrome in open employment may positively influence family quality of life. Services that facilitate functioning in ADL and assist the families in accessing suitable family supports have the potential to positively influence family quality of life.

Using hyperentanglement to enhance resolution, signal-to-noise ratio, and measurement time

NASA Astrophysics Data System (ADS)

Smith, James F.

2017-03-01

A hyperentanglement-based atmospheric imaging/detection system involving only a signal and an ancilla photon will be considered for optical and infrared frequencies. Only the signal photon will propagate in the atmosphere and its loss will be classical. The ancilla photon will remain within the sensor experiencing low loss. Closed form expressions for the wave function, normalization, density operator, reduced density operator, symmetrized logarithmic derivative, quantum Fisher information, quantum Cramer-Rao lower bound, coincidence probabilities, probability of detection, probability of false alarm, probability of error after M measurements, signal-to-noise ratio, quantum Chernoff bound, time-on-target expressions related to probability of error, and resolution will be provided. The effect of noise in every mode will be included as well as loss. The system will provide the basic design for an imaging/detection system functioning at optical or infrared frequencies that offers better than classical angular and range resolution. Optimization for enhanced resolution will be included. The signal-to-noise ratio will be increased by a factor equal to the number of modes employed during the hyperentanglement process. Likewise, the measurement time can be reduced by the same factor. The hyperentanglement generator will typically make use of entanglement in polarization, energy-time, orbital angular momentum and so on. Mathematical results will be provided describing the system's performance as a function of loss mechanisms and noise.

Balancing the Power-to-Load Ratio for a Novel Variable Geometry Wave Energy Converter with Nonideal Power Take-Off in Regular Waves: Preprint

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

Tom, Nathan M; Yu, Yi-Hsiang; Wright, Alan D

This work attempts to balance power absorption against structural loading for a novel variable geometry wave energy converter. The variable geometry consists of four identical flaps that will be opened in ascending order starting with the flap closest to the seafloor and moving to the free surface. The influence of a pitch motion constraint on power absorption when utilizing a nonideal power take-off (PTO) is examined and found to reduce the losses associated with bidirectional energy flow. The power-to-load ratio is evaluated using pseudo-spectral control to determine the optimum PTO torque based on a multiterm objective function. The pseudo-spectral optimalmore » control problem is extended to include load metrics in the objective function, which may now consist of competing terms. Separate penalty weights are attached to the surge-foundation force and PTO control torque to tune the optimizer performance to emphasize either power absorption or load shedding. PTO efficiency is not included in the objective function, but the penalty weights are utilized to limit the force and torque amplitudes, thereby reducing losses associated with bidirectional energy flow. Results from pseudo-spectral control demonstrate that shedding a portion of the available wave energy can provide greater reductions in structural loads and reactive power.« less

Psychological health of military children: longitudinal evaluation of a family-centered prevention program to enhance family resilience.

PubMed

Lester, Patricia; Stein, Judith A; Saltzman, William; Woodward, Kirsten; MacDermid, Shelley W; Milburn, Norweeta; Mogil, Catherine; Beardslee, William

2013-08-01

Family-centered preventive interventions have been proposed as relevant to mitigating psychological health risk and promoting resilience in military families facing wartime deployment and reintegration. This study evaluates the impact of a family-centered prevention program, Families OverComing Under Stress Family Resilience Training (FOCUS), on the psychological adjustment of military children. Two primary goals include (1) understanding the relationships of distress among family members using a longitudinal path model to assess relations at the child and family level and (2) determining pathways of program impact on child adjustment. Multilevel data analysis using structural equation modeling was conducted with deidentified service delivery data from 280 families (505 children aged 3-17) in two follow-up assessments. Standardized measures included service member and civilian parental distress (Brief Symptom Inventory, PTSD Checklist-Military), child adjustment (Strengths and Difficulties Questionnaire), and family functioning (McMaster Family Assessment Device). Distress was significantly related among the service member parent, civilian parent, and children. FOCUS improved family functioning, which in turn significantly reduced child distress at follow-up. Salient components of improved family functioning in reducing child distress mirrored resilience processes targeted by FOCUS. These findings underscore the public health potential of family-centered prevention for military families and suggest areas for future research. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Combinatory effect of mesenchymal stromal cells transplantation and quercetin after spinal cord injury in rat.

PubMed

Wang, X; Wang, Y-Y; Zhang, L-L; Li, G-T; Zhang, H-T

2018-05-01

To investigate the synergistic effects of quercetin (Qu) administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following spinal cord injury (SCI). HUMSCs were isolated, cultured and certificated via flow cytometry. Sixty Sprague-Dawley (SD) female rats were used and SCI models were made. All rats were divided into five experimental groups: culture medium treated group (n=28); HUSMCs + quercetin-treated group (n = 28); HUMSCs treated group (n=28); quercetin-treated group (n = 28); sham group (n = 20). Basso, Beattie, and Bresnahan (BBB) were used to assess neurological function recovery. Axons at the injury epicenter of the injury were checked by immunohistochemical analysis. Cystic cavity was measured and rat cytokine Luminex custom 8-plex kits (for interleukin (IL)-4, IL-1β, IL-6, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-β1) were checked. The combination treatment with Qu and delayed transplantation of HUMSCs after rat SCI improved neurological functional recovery, increased axonal preservation, promoted macrophage polarization, decreased the size of the cystic cavity, reduced the proinflammatory cytokines, including IL-1β and IL-6. Also, it increased anti-inflammatory cytokines, including IL-4, IL-10, and transforming growth factor (TGF)-β1. We showed that HUMSCs transplantation in combination with Qu was a potential strategy for reducing secondary damage and promoting functional recovery following SCI.

ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity.

PubMed

Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M T; Herrup, Karl; Plummer, Mark R

2016-07-01

Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. Copyright © 2016 the American Physiological Society.

ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity

PubMed Central

Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M. T.; Herrup, Karl

2016-01-01

Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm−/− animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm−/− mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. PMID:27075534

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant in persons with reduced kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Lyme and Dopaminergic Function: Hypothesizing Reduced Reward Deficiency Symptomatology by Regulating Dopamine Transmission

PubMed Central

Blum, Kenneth; Modestino, Edward J; Febo, Marcelo; Steinberg, Bruce; McLaughlin, Thomas; Fried, Lyle; Baron, David; Siwicki, David; Badgaiyan, Rajendra D

2017-01-01

The principal vector of Lyme disease in the United States is Ixodes scapularis: black legged or deer ticks. There is increased evidence that those infected may be plagued by anxiety or depression as well. Researchers have identified transcripts coding for two putative cytosolic sulfotransferases in these ticks, which recognized phenolic monoamines as their substrates. It is hypothesized that protracted Lyme disease sequelae may be due to impairment of dopaminergic function of the brain reward circuitry. The subsequent recombinant proteins exhibited sulfotransferase function against two neurotransmitters: dopamine and octopamine. This, in itself, can reduce dopamine function leading to many Reward Deficiency Syndrome behaviors, including depression and possibly, anxiety. In fact, it was shown that activity of Ixosc Sult 1 and Sult 2 in the Ixodid tick salivary glands might contain inactivation of the salivation signal through sulfonation of either dopamine or octopamine. This infraction results in a number of clinically observed mood changes, such as anxiety and depression. In fact, there are common symptoms observed for both Parkinson and Lyme diseases. The importance of understanding the mechanistic and neurobiological effects of Lyme on the central nervous system (CNS) provides the basis for pro-dopamine regulation as a treatment. WC 195 PMID:28736624

Lyme and Dopaminergic Function: Hypothesizing Reduced Reward Deficiency Symptomatology by Regulating Dopamine Transmission.

PubMed

Blum, Kenneth; Modestino, Edward J; Febo, Marcelo; Steinberg, Bruce; McLaughlin, Thomas; Fried, Lyle; Baron, David; Siwicki, David; Badgaiyan, Rajendra D

2017-05-01

The principal vector of Lyme disease in the United States is Ixodes scapularis: black legged or deer ticks. There is increased evidence that those infected may be plagued by anxiety or depression as well. Researchers have identified transcripts coding for two putative cytosolic sulfotransferases in these ticks, which recognized phenolic monoamines as their substrates. It is hypothesized that protracted Lyme disease sequelae may be due to impairment of dopaminergic function of the brain reward circuitry. The subsequent recombinant proteins exhibited sulfotransferase function against two neurotransmitters: dopamine and octopamine. This, in itself, can reduce dopamine function leading to many Reward Deficiency Syndrome behaviors, including depression and possibly, anxiety. In fact, it was shown that activity of Ixosc Sult 1 and Sult 2 in the Ixodid tick salivary glands might contain inactivation of the salivation signal through sulfonation of either dopamine or octopamine. This infraction results in a number of clinically observed mood changes, such as anxiety and depression. In fact, there are common symptoms observed for both Parkinson and Lyme diseases. The importance of understanding the mechanistic and neurobiological effects of Lyme on the central nervous system (CNS) provides the basis for pro-dopamine regulation as a treatment. WC 195.

Distance-Based Functional Diversity Measures and Their Decomposition: A Framework Based on Hill Numbers

PubMed Central

Chiu, Chun-Huo; Chao, Anne

2014-01-01

Hill numbers (or the “effective number of species”) are increasingly used to characterize species diversity of an assemblage. This work extends Hill numbers to incorporate species pairwise functional distances calculated from species traits. We derive a parametric class of functional Hill numbers, which quantify “the effective number of equally abundant and (functionally) equally distinct species” in an assemblage. We also propose a class of mean functional diversity (per species), which quantifies the effective sum of functional distances between a fixed species to all other species. The product of the functional Hill number and the mean functional diversity thus quantifies the (total) functional diversity, i.e., the effective total distance between species of the assemblage. The three measures (functional Hill numbers, mean functional diversity and total functional diversity) quantify different aspects of species trait space, and all are based on species abundance and species pairwise functional distances. When all species are equally distinct, our functional Hill numbers reduce to ordinary Hill numbers. When species abundances are not considered or species are equally abundant, our total functional diversity reduces to the sum of all pairwise distances between species of an assemblage. The functional Hill numbers and the mean functional diversity both satisfy a replication principle, implying the total functional diversity satisfies a quadratic replication principle. When there are multiple assemblages defined by the investigator, each of the three measures of the pooled assemblage (gamma) can be multiplicatively decomposed into alpha and beta components, and the two components are independent. The resulting beta component measures pure functional differentiation among assemblages and can be further transformed to obtain several classes of normalized functional similarity (or differentiation) measures, including N-assemblage functional generalizations of the classic Jaccard, Sørensen, Horn and Morisita-Horn similarity indices. The proposed measures are applied to artificial and real data for illustration. PMID:25000299

Distance-based functional diversity measures and their decomposition: a framework based on Hill numbers.

PubMed

Chiu, Chun-Huo; Chao, Anne

2014-01-01

Hill numbers (or the "effective number of species") are increasingly used to characterize species diversity of an assemblage. This work extends Hill numbers to incorporate species pairwise functional distances calculated from species traits. We derive a parametric class of functional Hill numbers, which quantify "the effective number of equally abundant and (functionally) equally distinct species" in an assemblage. We also propose a class of mean functional diversity (per species), which quantifies the effective sum of functional distances between a fixed species to all other species. The product of the functional Hill number and the mean functional diversity thus quantifies the (total) functional diversity, i.e., the effective total distance between species of the assemblage. The three measures (functional Hill numbers, mean functional diversity and total functional diversity) quantify different aspects of species trait space, and all are based on species abundance and species pairwise functional distances. When all species are equally distinct, our functional Hill numbers reduce to ordinary Hill numbers. When species abundances are not considered or species are equally abundant, our total functional diversity reduces to the sum of all pairwise distances between species of an assemblage. The functional Hill numbers and the mean functional diversity both satisfy a replication principle, implying the total functional diversity satisfies a quadratic replication principle. When there are multiple assemblages defined by the investigator, each of the three measures of the pooled assemblage (gamma) can be multiplicatively decomposed into alpha and beta components, and the two components are independent. The resulting beta component measures pure functional differentiation among assemblages and can be further transformed to obtain several classes of normalized functional similarity (or differentiation) measures, including N-assemblage functional generalizations of the classic Jaccard, Sørensen, Horn and Morisita-Horn similarity indices. The proposed measures are applied to artificial and real data for illustration.

Social functioning and internalized stigma in individuals diagnosed with substance use disorder.

PubMed

Can, Ganime; Tanrıverdi, Derya

2015-12-01

The aim of this descriptive study was to determine social functioning and internalized stigma in individuals with substance use disorder. The study sample consisted of 105 patients diagnosed with substance use disorder according to the DSM-IV-TR diagnostic criteria. A Descriptive Information Form, Internalized Stigma of Mental Illness Scale (ISMI) and Social Functioning Scale (SFS) were used for data collection. Average total SFS score of the patients was 103.25±25.09 points, indicating an intermediate level of social functioning. Average total ISMI score of patients was 2.92±0.48 points, reflecting a high level of internalized stigma. A negative significant association was observed between the internalized stigma levels and social functioning of patients. These results suggest that rehabilitation of substance users should include counseling services in order to reduce internal perception of stigma and improve their social functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunotoxicity assessment for the novel Spleen tyrosine kinase inhibitor R406

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

Zhu Yanhong; Herlaar, Ellen; Masuda, Esteban S.

2007-06-15

Spleen tyrosine kinase (Syk) is a novel pharmaceutical target for treatment of allergic, autoimmune, and neoplastic disorders. Previous studies have indicated that Syk signaling plays critical roles in regulating the lymphohematopoietic system. These observations prompted us to investigate whether inhibition of Syk would promote immunotoxicity. In a series of studies, rats were treated orally with R406, at dose levels up to and including 100 mg/kg/day (or its prodrug R788 at dose levels up to and including 100 mg/kg/day, reduced to 50 mg/kg/day for females as MTD was exceeded), a potent Syk inhibitor, twice daily for 28 days. In addition tomore » standard toxicological assessments, immunophenotyping by flow cytometric analysis, and a study of humoral immune response measuring anti-KLH IgM and IgG levels, were undertaken. Other immunotoxicity studies included three host resistance models in female Balb/c mice to further ascertain effects of R406 on innate and acquired immunity. Following R406 treatment, expected immunomodulating effects (e.g., decreased thymic and spleen weight, hypocellularity of bone marrow, and reduced lymphocyte counts, including T and B cells) were observed in the rat studies. These changes essentially resolved during a 14-day treatment-free recovery period. A KLH challenge in rats demonstrated no adverse effects on IgG or IgM response. R788/406, administered orally at dose levels up to and including 80 mg/kg/day for 28 days, did not affect bacterial or viral clearance in the Listeria, Streptococcal, or Influenza host resistance mouse models, respectively. This correlated with previous in vitro macrophage and neutrophil function assays (assessing migration, phagocytosis, oxidative burst and microbicidal activity), which revealed that R406 did not adversely affect macrophage or neutrophil function in innate immune responses. Collectively, these results demonstrate that R406 has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect, suggesting that inhibition of Syk might not lead to unacceptable mechanism-based adverse effects.« less

Abnormal cerebral functional connectivity in esophageal cancer patients with theory of mind deficits in resting state.

PubMed

Cao, Yin; Xiang, JianBo; Qian, Nong; Sun, SuPing; Hu, LiJun; Yuan, YongGui

2015-01-01

To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P < 0.05). In the resting state, the functional connectivity is abnormal in the cerebral regions in the DMN of esophageal cancer patients with theory of mind deficits. The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer.

Soliton-cnoidal interactional wave solutions for the reduced Maxwell-Bloch equations

NASA Astrophysics Data System (ADS)

Huang, Li-Li; Qiao, Zhi-Jun; Chen, Yong

2018-02-01

Based on nonlocal symmetry method, localized excitations and interactional solutions are investigated for the reduced Maxwell-Bloch equations. The nonlocal symmetries of the reduced Maxwell-Bloch equations are obtained by the truncated Painleve expansion approach and the Mobious invariant property. The nonlocal symmetries are localized to a prolonged system by introducing suitable auxiliary dependent variables. The extended system can be closed and a novel Lie point symmetry system is constructed. By solving the initial value problems, a new type of finite symmetry transformations is obtained to derive periodic waves, Ma breathers and breathers travelling on the background of periodic line waves. Then rich exact interactional solutions are derived between solitary waves and other waves including cnoidal waves, rational waves, Painleve waves, and periodic waves through similarity reductions. In particular, several new types of localized excitations including rogue waves are found, which stem from the arbitrary function generated in the process of similarity reduction. By computer numerical simulation, the dynamics of these localized excitations and interactional solutions are discussed, which exhibit meaningful structures.

The effect of spectacle treatment in patients with mild traumatic brain injury: a pilot study.

PubMed

Johansson, Jan; Nygren de Boussard, Catharina; Öqvist Seimyr, Gustaf; Pansell, Tony

2017-05-01

Visual symptoms and dysfunctions may be a part of the long-term issues following mild traumatic brain injury. These issues may have an impact on near work and reading, and thus affect activities of daily life and the ability to return to work. The purpose of the study was to assess the effect of spectacle treatment on near work-related visual symptoms, visual function and reading performance in patients with persisting symptoms after mild traumatic brain injury. Eight patients with persisting symptoms after mild traumatic brain injury and anomalies of binocular function were included. Binocular function, visual symptoms and reading performance were assessed before and after spectacle treatment. Reading eye movements were recorded with eye tracking. Four patients showed a considerable symptom reduction along with minor improvement in clinical visual measures. Reading performance improved in four patients; however, the relationship to symptom reduction was inconsistent. The improvement was correlated to reduced average number of fixations per word (r = -0.89, p = 0.02), reduced proportion of regressive saccades (r = -0.93, p = 0.01) and a significant increase of mean progressive saccade length (p = 0.03). This pilot study found that spectacle treatment, specifically directed at optimising near task visual function, significantly reduced symptoms in 50 per cent of patients and improved reading performance in 50 per cent. While promising, lack of placebo control and lack of correlation between reading performance and symptom improvements means we cannot decipher mechanisms without further study. © 2016 Optometry Australia.

Method and apparatus for calibrating a tiled display

NASA Technical Reports Server (NTRS)

Chen, Chung-Jen (Inventor); Johnson, Michael J. (Inventor); Chandrasekhar, Rajesh (Inventor)

2001-01-01

A display system that can be calibrated and re-calibrated with a minimal amount of manual intervention. To accomplish this, one or more cameras are provided to capture an image of the display screen. The resulting captured image is processed to identify any non-desirable characteristics, including visible artifacts such as seams, bands, rings, etc. Once the non-desirable characteristics are identified, an appropriate transformation function is determined. The transformation function is used to pre-warp the input video signal that is provided to the display such that the non-desirable characteristics are reduced or eliminated from the display. The transformation function preferably compensates for spatial non-uniformity, color non-uniformity, luminance non-uniformity, and other visible artifacts.

The aging neuromuscular system and motor performance

PubMed Central

Keenan, Kevin G.

2016-01-01

Age-related changes in the basic functional unit of the neuromuscular system, the motor unit, and its neural inputs have a profound effect on motor function, especially among the expanding number of old (older than ∼60 yr) and very old (older than ∼80 yr) adults. This review presents evidence that age-related changes in motor unit morphology and properties lead to impaired motor performance that includes 1) reduced maximal strength and power, slower contractile velocity, and increased fatigability; and 2) increased variability during and between motor tasks, including decreased force steadiness and increased variability of contraction velocity and torque over repeat contractions. The age-related increase in variability of motor performance with aging appears to involve reduced and more variable synaptic inputs that drive motor neuron activation, fewer and larger motor units, less stable neuromuscular junctions, lower and more variable motor unit action potential discharge rates, and smaller and slower skeletal muscle fibers that coexpress different myosin heavy chain isoforms in the muscle of older adults. Physical activity may modify motor unit properties and function in old men and women, although the effects on variability of motor performance are largely unknown. Many studies are of cross-sectional design, so there is a tremendous opportunity to perform high-impact and longitudinal studies along the continuum of aging that determine 1) the influence and cause of the increased variability with aging on functional performance tasks, and 2) whether lifestyle factors such as physical exercise can minimize this age-related variability in motor performance in the rapidly expanding numbers of very old adults. PMID:27516536

Electronic structure of stoichiometric and reduced ZnO from periodic relativistic all electron hybrid density functional calculations using numeric atom-centered orbitals.

PubMed

Viñes, Francesc; Illas, Francesc

2017-03-30

The atomic and electronic structure of stoichiometric and reduced ZnO wurtzite has been studied using a periodic relativistic all electron hybrid density functional (PBE0) approach and numeric atom-centered orbital basis set with quality equivalent to aug-cc-pVDZ. To assess the importance of relativistic effects, calculations were carried out without and with explicit inclusion of relativistic effects through the zero order regular approximation. The calculated band gap is ∼0.2 eV smaller than experiment, close to previous PBE0 results including relativistic calculation through the pseudopotential and ∼0.25 eV smaller than equivalent nonrelativistic all electron PBE0 calculations indicating possible sources of error in nonrelativistic all electron density functional calculations for systems containing elements with relatively high atomic number. The oxygen vacancy formation energy converges rather fast with the supercell size, the predicted value agrees with previously hybrid density functional calculations and analysis of the electronic structure evidences the presence of localized electrons at the vacancy site with a concomitant well localized peak in the density of states ∼0.5 eV above the top of the valence band and a significant relaxation of the Zn atoms near to the oxygen vacancy. Finally, present work shows that accurate results can be obtained in systems involving large supercells containing up to ∼450 atoms using a numeric atomic-centered orbital basis set within a full all electron description including scalar relativistic effects at an affordable cost. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Transcriptional coactivators PGC-1α and PGC-lβ control overlapping programs required for perinatal maturation of the heart

PubMed Central

Lai, Ling; Leone, Teresa C.; Zechner, Christoph; Schaeffer, Paul J.; Kelly, Sean M.; Flanagan, Daniel P.; Medeiros, Denis M.; Kovacs, Attila; Kelly, Daniel P.

2008-01-01

Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARγ coactivator-1 (PGC-1) α and β have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1α and PGC-1β (PGC-1αβ−/− mice) were generated to investigate the convergence of their functions in vivo. The phenotype of PGC-1β−/− mice was minimal under nonstressed conditions, including normal heart function, similar to that of PGC-1α−/− mice generated previously. In striking contrast to the singly deficient PGC-1 lines, PGC-1αβ−/− mice died shortly after birth with small hearts, bradycardia, intermittent heart block, and a markedly reduced cardiac output. Cardiac-specific ablation of the PGC-1β gene on a PGC-1α-deficient background phenocopied the generalized PGC-1αβ−/− mice. The hearts of the PGC-1αβ−/− mice exhibited signatures of a maturational defect including reduced growth, a late fetal arrest in mitochondrial biogenesis, and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT) of PGC-1αβ−/− mice also exhibited a severe abnormality in function and mitochondrial density. We conclude that PGC-1α and PGC-1β share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT. PMID:18628400

Age‐related alterations in immune responses to West Nile virus infection

PubMed Central

2016-01-01

Summary West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti‐viral immune genes, but age is the most well‐defined risk factor for susceptibility to severe disease. Ageing is associated with distinct changes in immune cells and a decline in immune function leading to increased susceptibility to infection and reduced responses to vaccination. WNV is detected by pathogen recognition receptors including Toll‐like receptors (TLRs), which show reduced expression and function in ageing. Neutrophils, monocyte/macrophages and dendritic cells, which first recognize and respond to infection, show age‐related impairment of many functions relevant to anti‐viral responses. Natural killer cells control many viral infections and show age‐related changes in phenotype and functional responses. A role for the regulatory receptors Mertk and Axl in blood–brain barrier permeability and in facilitating viral uptake through phospholipid binding may be relevant for susceptibility to WNV, and age‐related up‐regulation of Axl has been noted previously in human dendritic cells. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals and identify potential avenues for therapeutic approaches: an especially relevant goal, as the world's populating is ageing. PMID:27612657

Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function

PubMed Central

Lee, Shirley Y.; Pullen, Lester; Virgil, Daniel J.; Castañeda, Carlos A.; Abeykoon, Dulith; Bolon, Daniel N. A.; Fushman, David

2014-01-01

Mutations at solvent inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understood for most systems. Here, we determined the effects of alanine mutations at all 15 core positions in ubiquitin on function in yeast. The majority (13 of 15) of alanine substitutions supported yeast growth as the sole ubiquitin. The two null mutants (I30A and L43A) were both less stable to temperature-induced unfolding in vitro than wild-type, but were well folded at physiological temperatures. Heteronuclear NMR studies indicated that the L43A mutation reduces temperature stability while retaining a ground-state structure similar to wild-type. This structure enables L43A to bind to common ubiquitin receptors in vitro. Many of the core alanine ubiquitin mutants, including one of the null variants (I30A), exhibited an increased accumulation of high molecular weight species, suggesting that these mutants caused a defect in the processing of ubiquitin-substrate conjugates. In contrast, L43A exhibited a unique accumulation pattern with reduced levels of high molecular weight species and undetectable levels of free ubiquitin. When conjugation to other proteins was blocked, L43A ubiquitin accumulated as free ubiquitin in yeast. Based on these findings we speculate that ubiquitin's stability to unfolding may be required for efficient recycling during proteasome-mediated substrate degradation. PMID:24361330

Altered Resting State Functional Connectivity in Young Survivors of Acute Lymphoblastic Leukemia

PubMed Central

Kesler, Shelli R.; Gugel, Meike; Pritchard-Berman, Mika; Lee, Clement; Kutner, Emily; Hosseini, S.M. Hadi; Dahl, Gary; Lacayo, Norman

2014-01-01

Background Chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) has been associated with long-term cognitive impairments in some patients. However, the neurobiologic mechanisms underlying these impairments, particularly in young survivors, are not well understood. This study aimed to examine intrinsic functional brain connectivity in pediatric ALL and its relationship with cognitive status. Procedure We obtained resting state functional magnetic resonance imaging (rsfMRI) and cognitive testing data from 15 ALL survivors age 8–15 years and 14 matched healthy children. The ALL group had a history of intrathecal chemotherapy treatment but were off-therapy for at least 6 months at the time of enrollment. We used seed-based analyses to compare intrinsic functional brain network connectivity between the groups. We also explored correlations between connectivity and cognitive performance, demographic, medical, and treatment variables. Results We demonstrated significantly reduced connectivity between bilateral hippocampus, left inferior occipital, left lingual gyrus, bilateral calcarine sulcus, and right amygdala in the ALL group compared to controls. The ALL group also showed regions of functional hyperconnectivity including right lingual gyrus, precuneus, bilateral superior occipital lobe, and right inferior occipital lobe. Functional hypoconnectivity was associated with reduced cognitive function as well as younger age at diagnosis in the ALL group. Conclusions This is the first study to demonstrate that intrinsic functional brain connectivity is disrupted in pediatric ALL following chemotherapy treatment. These results help explain cognitive dysfunction even when objective test performance is seemingly normal. Children diagnosed at a younger age may show increased vulnerability to altered functional brain connectivity. PMID:24619953

Regulation of Satellite Cell Function in Sarcopenia

PubMed Central

Alway, Stephen E.; Myers, Matthew J.; Mohamed, Junaith S.

2014-01-01

The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell) function that is impacted by the environment (niche) of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse, or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins, and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration). While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function. PMID:25295003

Cordyceps sinensis (a traditional Chinese medicine) for kidney transplant recipients.

PubMed

Hong, Tao; Zhang, Minghua; Fan, Junming

2015-10-12

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease (ESKD). Rising ESKD prevalence has substantially increased numbers of kidney transplants performed. Maintenance immunosuppression is long-term treatment to prevent acute rejection and deterioration of graft function. Although immunosuppressive treatment using drugs such as calcineurin inhibitors (CNIs, such as cyclosporin A (CsA) or tacrolimus) reduce acute rejection rates, long-term allograft survival rates are not significantly enhanced. CNI-related adverse effects contribute to reduced quality of life among kidney transplant recipients. Adjuvant immunosuppressive therapies that could offer a synergetic immunosuppressive effect, while minimising toxicity and reducing side effects, have been explored recently. Cordyceps sinensis, (Cordyceps) a traditional Chinese medicine, is used as an adjuvant immunosuppressive agent in maintenance treatment for kidney transplantation recipients in China, but there is no consensus about its use as an adjuvant immunosuppressive treatment for kidney transplantation recipients. This review aimed to evaluate the benefits and potential adverse effects of Cordyceps as an adjuvant immunosuppressive treatment for kidney transplant recipients. We searched the Cochrane Kidney and Transplant Specialised Register through contact with the Trials Search Co-ordinator to 7 September 2015 using search terms relevant to this review. We also searched Chinese language databases and other resources. We included all randomised controlled trials (RCTs) and quasi-RCTs evaluating the benefits and potential side effects of Cordyceps sinensis for kidney transplant recipients, irrespective of blinding or publication language. An inclusion criterion was that baseline immunosuppressive therapy must be the same in all study arms. Two authors extracted data. We derived risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Our review included five studies (six reports; 447 participants) that assessed Cordyceps. Limited reporting of study methods and data meant that all included studies were assessed as having unclear risks of bias. The studies investigated Cordyceps compared with azathioprine (AZA) (4 studies, 265 participants) and Cordyceps plus low dose CsA versus standard dose CsA (1 study, 182 participants).Compared with AZA, Cordyceps showed no significant difference in graft or patient survival, but improved graft function and may reduce acute rejection episodes. Anaemia, leucopenia, and liver function improved, and incidence of infection may also be reduced.Compared with low dose CsA versus standard dose CsA, Cordyceps did not demonstrate any statistically significant differences in patient survival, graft loss, acute rejection or allograft function. There was limited low quality evidence to suggest benefits in pulmonary infection, serum albumin, serum uric acid levels, CNI nephrotoxicity and hepatotoxicity.None of the included studies reported on quality of life, and follow-up was short-term (three months to one year). Given the limited number of small studies, and high risk of bias, results should be interpreted with caution. Although there were some favourable aspects associated with Cordyceps, longer-term studies are needed to clarify any benefit-harm trade-off. Future studies should investigate the use of Cordyceps in combination with other immunosuppressive agents such as tacrolimus, mycophenolate mofetil or induction therapy. Such studies also need to be appropriately sized and powered.

Certified Normal: Alzheimer’s Disease Biomarkers and Normative Estimates of Cognitive Functioning

PubMed Central

Hassenstab, Jason; Chasse, Rachel; Grabow, Perri; Benzinger, Tammie L.S.; Fagan, Anne M.; Xiong, Chengjie; Jasielec, Mateusz; Grant, Elizabeth; Morris, John C.

2016-01-01

Normative samples drawn from older populations may unintentionally include individuals with preclinical Alzheimer’s disease (AD) pathology, resulting in reduced means, increased variability, and overestimation of age-effects on cognitive performance. 264 cognitively normal (CDR=0) older adults were classified as biomarker-negative (“Robust Normal,” n=177) or biomarker-positive (“Preclinical Alzheimer’s Disease” (PCAD), n=87) based on amyloid imaging, cerebrospinal fluid biomarkers, and hippocampal volumes. PCAD participants performed worse than Robust Normals on nearly all cognitive measures. Removing PCAD participants from the normative sample yielded higher means and less variability on episodic memory, visuospatial ability, and executive functioning measures. These results were more pronounced in participants aged 75 and older. Notably, removing PCAD participants from the sample significantly reduced age effects across all cognitive domains. Applying norms from the Robust Normal sample to a separate cohort did not improve CDR classification when using standard deviation cutoff scores. Overall, removing individuals with biomarker evidence of preclinical AD improves normative sample quality and substantially reduces age-effects on cognitive performance, but provides no substantive benefit for diagnostic classifications. PMID:27255812

Impaired β-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor.

PubMed

Gray, David L; Allen, John A; Mente, Scot; O'Connor, Rebecca E; DeMarco, George J; Efremov, Ivan; Tierney, Patrick; Volfson, Dmitri; Davoren, Jennifer; Guilmette, Edward; Salafia, Michelle; Kozak, Rouba; Ehlers, Michael D

2018-02-14

Selective activation of dopamine D1 receptors (D1Rs) has been pursued for 40 years as a therapeutic strategy for neurologic and psychiatric diseases due to the fundamental role of D1Rs in motor function, reward processing, and cognition. All known D1R-selective agonists are catechols, which are rapidly metabolized and desensitize the D1R after prolonged exposure, reducing agonist response. As such, drug-like selective D1R agonists have remained elusive. Here we report a novel series of selective, potent non-catechol D1R agonists with promising in vivo pharmacokinetic properties. These ligands stimulate adenylyl cyclase signaling and are efficacious in a rodent model of Parkinson's disease after oral administration. They exhibit distinct binding to the D1R orthosteric site and a novel functional profile including minimal receptor desensitization, reduced recruitment of β-arrestin, and sustained in vivo efficacy. These results reveal a novel class of D1 agonists with favorable drug-like properties, and define the molecular basis for catechol-specific recruitment of β-arrestin to D1Rs.

Neither pre-operative education or a minimally invasive procedure have any influence on the recovery time after total hip replacement.

PubMed

Biau, David Jean; Porcher, Raphael; Roren, Alexandra; Babinet, Antoine; Rosencher, Nadia; Chevret, Sylvie; Poiraudeau, Serge; Anract, Philippe

2015-08-01

The purpose of this study was to evaluate pre-operative education versus no education and mini-invasive surgery versus standard surgery to reach complete independence. We conducted a four-arm randomized controlled trial of 209 patients. The primary outcome criterion was the time to reach complete functional independence. Secondary outcomes included the operative time, the estimated total blood loss, the pain level, the dose of morphine, and the time to discharge. There was no significant effect of either education (HR: 1.1; P = 0.77) or mini-invasive surgery (HR: 1.0; 95 %; P = 0.96) on the time to reach complete independence. The mini-invasive surgery group significantly reduced the total estimated blood loss (P = 0.0035) and decreased the dose of morphine necessary for titration in the recovery (P = 0.035). Neither pre-operative education nor mini-invasive surgery reduces the time to reach complete functional independence. Mini-invasive surgery significantly reduces blood loss and the need for morphine consumption.

Lactobacillus johnsonii Supplementation Attenuates Respiratory Viral Infection via Metabolic Reprogramming and Immune Cell Modulation

PubMed Central

Fonseca, Wendy; Lucey, Kaitlyn; Jang, Sihyug; Fujimura, Kei E.; Rasky, Andrew; Ting, Hung-An; Petersen, Julia; Johnson, Christine C.; Boushey, Homer A.; Zoratti, Edward; Ownby, Dennis R.; Levine, Albert M.; Bobbit, Kevin R.

2017-01-01

Summary Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii-supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii-supplementation reduced airway Th2 cytokines, dendritic cell function, increased T-regulatory cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone-marrow derived dendritic cells (BMDC) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice, or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice, or with wild-type derived BMDCs pre-treated with plasma from L. johnsonii-supplemented mice, reduced airway pathologic responses to infection in recipient animals. Thus, L. johnsonii-supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function. PMID:28295020

Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.

PubMed

Fonseca, W; Lucey, K; Jang, S; Fujimura, K E; Rasky, A; Ting, H-A; Petersen, J; Johnson, C C; Boushey, H A; Zoratti, E; Ownby, D R; Levine, A M; Bobbit, K R; Lynch, S V; Lukacs, N W

2017-11-01

Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.

Screening for diets that reduce urinary nitrogen excretion and methane emissions while maintaining or increasing production by dairy cows.

PubMed

Gregorini, Pablo; Beukes, Pierre C; Dalley, Dawn; Romera, Alvaro J

2016-05-01

Farmers face complex decisions at the time to feed animals, trying to achieve production goals while contemplating social and environmental constraints. Our purpose was to facilitate such decision making for pastoral dairy farmers, aiming to reduce urinary N (UN) and methane emissions (CH4), while maintaining or increasing milk production (MP). There is a number of feeds the farmers can choose from and combine. We used 50 feeds (forages and grains) combined systematically in different proportions producing 11,526 binary diets. Diets were screened, using an a posteriori approach and a Pareto front (PF) analysis of model (Molly) outputs. The objective was to identify combinations with the best possible compromise (i.e. frontier) between UN, CH4, and MP. Using high MP and low UN as objective functions, PF included 10, 14, 12 and 50 diets, for non-lactating, early-, mid- and late-lactation periods, with cereals and beets featuring strongly. Using the same objective functions, but including ryegrass as dietary base PF included 2, 4, 8 and 4 diets for those periods. Therefore, from a wide range of diets, farmers could choose from few feeds combined into binary diets to reduce UN while maintaining or increasing MP. If the intention is maintaining pasture-based systems, there are fewer suitable options. Reducing UN will simply require dilution of N supplied by pasture by supplementing low N conserved forages. The results also evidence the risk of pollution swapping, reaching the frontier means arriving at a point where trade-off decisions need to be made. Any further reduction in UN implies an increment in CH4, or reduction in CH4 emissions increases UN. There is no perfect diet to optimize all objectives simultaneously; but if the current diet is not in the frontier some options can offset pollution swapping. The choice is with the farmers and conditioned by their context. Copyright © 2016 Elsevier B.V. All rights reserved.

Coated article and method of making

NASA Technical Reports Server (NTRS)

Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

2003-01-01

An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

Coated article and method of making

NASA Technical Reports Server (NTRS)

Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)

2002-01-01

An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.

Generalizations of Tikhonov's regularized method of least squares to non-Euclidean vector norms

NASA Astrophysics Data System (ADS)

Volkov, V. V.; Erokhin, V. I.; Kakaev, V. V.; Onufrei, A. Yu.

2017-09-01

Tikhonov's regularized method of least squares and its generalizations to non-Euclidean norms, including polyhedral, are considered. The regularized method of least squares is reduced to mathematical programming problems obtained by "instrumental" generalizations of the Tikhonov lemma on the minimal (in a certain norm) solution of a system of linear algebraic equations with respect to an unknown matrix. Further studies are needed for problems concerning the development of methods and algorithms for solving reduced mathematical programming problems in which the objective functions and admissible domains are constructed using polyhedral vector norms.

Evaluation of an Atmosphere Revitalization Subsystem for Deep Space Exploration Missions

NASA Technical Reports Server (NTRS)

Perry, Jay L.; Abney, Morgan B.; Conrad, Ruth E.; Frederick, Kenneth R.; Greenwood, Zachary W.; Kayatin, Matthew J.; Knox, James C.; Newton, Robert L.; Parrish, Keith J.; Takada, Kevin C.;

Functionally Graded Adhesives for Composite Joints

NASA Technical Reports Server (NTRS)

Stapleton, Scott E.; Waas, Anthony M.; Arnold, Steven M.

2012-01-01

Adhesives with functionally graded material properties are being considered for use in adhesively bonded joints to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. An enhanced joint finite element, which uses an analytical formulation to obtain exact shape functions, is used to model the joint. Furthermore, proof of concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint.

Reduced Abundance and Subverted Functions of Proteins in Prion-Like Diseases: Gained Functions Fascinate but Lost Functions Affect Aetiology.

PubMed

Allison, W Ted; DuVal, Michèle G; Nguyen-Phuoc, Kim; Leighton, Patricia L A

2017-10-24

Prions have served as pathfinders that reveal many aspects of proteostasis in neurons. The recent realization that several prominent neurodegenerative diseases spread via a prion-like mechanism illuminates new possibilities for diagnostics and therapeutics. Thus, key proteins in Alzheimer Disease and Amyotrophic lateral sclerosis (ALS), including amyloid-β precursor protein, Tau and superoxide dismutase 1 (SOD1), spread to adjacent cells in their misfolded aggregated forms and exhibit template-directed misfolding to induce further misfolding, disruptions to proteostasis and toxicity. Here we invert this comparison to ask what these prion-like diseases can teach us about the broad prion disease class, especially regarding the loss of these key proteins' function(s) as they misfold and aggregate. We also consider whether functional amyloids might reveal a role for subverted protein function in neurodegenerative disease. Our synthesis identifies SOD1 as an exemplar of protein functions being lost during prion-like protein misfolding, because SOD1 is inherently unstable and loses function in its misfolded disease-associated form. This has under-appreciated parallels amongst the canonical prion diseases, wherein the normally folded prion protein, PrP C , is reduced in abundance in fatal familial insomnia patients and during the preclinical phase in animal models, apparently via proteostatic mechanisms. Thus while template-directed misfolding and infectious properties represent gain-of-function that fascinates proteostasis researchers and defines (is required for) the prion(-like) diseases, loss and subversion of the functions attributed to hallmark proteins in neurodegenerative disease needs to be integrated into design towards effective therapeutics. We propose experiments to uniquely test these ideas.

Does renal ageing affect survival?

PubMed

Razzaque, M Shawkat

2007-10-01

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

Enhancing lithium-sulphur battery performance by strongly binding the discharge products on amino-functionalized reduced graphene oxide.

PubMed

Wang, Zhiyu; Dong, Yanfeng; Li, Hongjiang; Zhao, Zongbin; Wu, Hao Bin; Hao, Ce; Liu, Shaohong; Qiu, Jieshan; Lou, Xiong Wen David

2014-09-25

Lithium-sulphur batteries are one very appealing power source with high energy density. But their practical use is still hindered by several issues including short lifespan, low efficiency and safety concern from the lithium anode. Polysulphide dissolution and insulating nature of sulphur are generally considered responsible for the capacity degradation. However, the detachment of discharge products, that is, highly polar lithium sulphides, from nonpolar carbon matrix (for example, graphene) has been rarely studied as one critical factor. Here we report the strongly covalent stabilization of sulphur and its discharge products on amino-functionalized reduced graphene oxide that enables stable capacity retention of 80% for 350 cycles with high capacities and excellent high-rate response up to 4 C. The present study demonstrates a feasible and effective strategy to solve the long-term cycling difficulty for lithium-sulphur batteries and also helps to understand the capacity decay mechanism involved.

RETScreen Plus Software Tutorial

NASA Technical Reports Server (NTRS)

Ganoe, Rene D.; Stackhouse, Paul W., Jr.; DeYoung, Russell J.

2014-01-01

Greater emphasis is being placed on reducing both the carbon footprint and energy cost of buildings. A building's energy usage depends upon many factors one of the most important is the local weather and climate conditions to which it's electrical, heating and air conditioning systems must respond. Incorporating renewable energy systems, including solar systems, to supplement energy supplies and increase energy efficiency is important to saving costs and reducing emissions. Also retrofitting technologies to buildings requires knowledge of building performance in its current state, potential future climate state, projection of potential savings with capital investment, and then monitoring the performance once the improvements are made. RETScreen Plus is a performance analysis software module that supplies the needed functions of monitoring current building performance, targeting projected energy efficiency improvements and verifying improvements once completed. This tutorial defines the functions of RETScreen Plus as well as outlines the general procedure for monitoring and reporting building energy performance.

Exercise therapy for fibromyalgia.

PubMed

Busch, Angela J; Webber, Sandra C; Brachaniec, Mary; Bidonde, Julia; Bello-Haas, Vanina Dal; Danyliw, Adrienne D; Overend, Tom J; Richards, Rachel S; Sawant, Anuradha; Schachter, Candice L

2011-10-01

Fibromyalgia syndrome, a chronic condition typically characterized by widespread pain, nonrestorative sleep, fatigue, cognitive dysfunction, and other somatic symptoms, negatively impacts physical and emotional function and reduces quality of life. Exercise is commonly recommended in the management of people with fibromyalgia, and interest in examining exercise benefits for those with the syndrome has grown substantially over the past 25 years. Research supports aerobic and strength training to improve physical fitness and function, reduce fibromyalgia symptoms, and improve quality of life. However, other forms of exercise (e.g., tai chi, yoga, Nordic walking, vibration techniques) and lifestyle physical activity also have been investigated to determine their effects. This paper highlights findings from recent randomized controlled trials and reviews of exercise for people with fibromyalgia, and includes information regarding factors that influence response and adherence to exercise to assist clinicians with exercise and physical activity prescription decision-making to optimize health and well-being.

Functional polysaccharides from Grifola frondosa aqueous extract inhibit atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Park, Hyeon Soo; Hwang, Yong Hyeon; Kim, Mun Ki; Hong, Gyeong Eun; Lee, Ho Jeong; Nagappan, Arulkumar; Yumnam, Silvia; Kim, Eun Hee; Heo, Jeong Doo; Lee, Sang Joon; Won, Chung Kil; Kim, Gon Sup

2015-01-01

Grifola frondosa (GF), distributed widely in far east Asia including Korea, is popularly used as traditional medicines and health supplementary foods, especially for enhancing the immune functions of the body. To extend the application of GF polysaccharides (GFP) for atopic dermatitis (AD), we investigated the effects of GFP on the 2,4-dinitrochlorobenzene-induced AD-like skin lesion in NC/Nga mice. GFP treatment significantly reduced the dorsa skin dermatitis score and combination treatment with GFP, and dexamethasone has a synergistic effect in AD-like skin lesion by reduced Serum IgE, mast cells infiltration, and cytokines expression. These results indicate that GFP suppressed the AD-like skin lesions by controlling the Th-1/Th-2-type cytokines in NC/Nga mice. These findings strongly suggest that GFP can be useful for AD patients as a novel therapeutic agent and might be used for corticosteroids replacement or supplement agent.

A specific role for septohippocampal acetylcholine in memory?

PubMed Central

Easton, Alexander; Douchamps, Vincent; Eacott, Madeline; Lever, Colin

2012-01-01

Acetylcholine has long been implicated in memory, including hippocampal-dependent memory, but the specific role for this neurotransmitter is difficult to identify in human neuropsychology. Here, we review the evidence for a mechanistic model of acetylcholine function within the hippocampus and consider its explanatory power for interpreting effects resulting from both pharmacological anticholinergic manipulations and lesions of the cholinergic input to the hippocampus in animals. We argue that these effects indicate that acetylcholine is necessary for some, but not all, hippocampal-dependent processes. We review recent evidence from lesion, pharmacological and electrophysiological studies to support the view that a primary function of septohippocampal acetylcholine is to reduce interference in the learning process by adaptively timing and separating encoding and retrieval processes. We reinterpret cholinergic-lesion based deficits according to this view and propose that acetylcholine reduces the interference elicited by the movement of salient locations between events. PMID:22884957

Decreased subcortical cholinergic arousal in focal seizures

PubMed Central

Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal

2015-01-01

SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258

Tzfp represses the androgen receptor in mouse testis.

PubMed

Furu, Kari; Klungland, Arne

2013-01-01

The testis zinc finger protein (Tzfp), also known as Repressor of GATA, belongs to the BTB/POZ zinc finger family of transcription factors and is thought to play a role in spermatogenesis due to its remarkably high expression in testis. Despite many attempts to find the in vivo role of the protein, the molecular function is still largely unknown. Here, we address this issue using a novel mouse model with a disrupted Tzfp gene. Homozygous Tzfp null mice are born at reduced frequency but appear viable and fertile. Sertoli cells in testes lacking Tzfp display an increase in Androgen Receptor (AR) signaling, and several genes in the testis, including Gata1, Aie1 and Fanc, show increased expression. Our results indicate that Tzfp function as a transcriptional regulator and that loss of the protein leads to alterations in AR signaling and reduced number of apoptotic cells in the testicular tubules.

Design of efficient stiffened shells of revolution

NASA Technical Reports Server (NTRS)

Majumder, D. K.; Thornton, W. A.

1976-01-01

A method to produce efficient piecewise uniform stiffened shells of revolution is presented. The approach uses a first order differential equation formulation for the shell prebuckling and buckling analyses and the necessary conditions for an optimum design are derived by a variational approach. A variety of local yielding and buckling constraints and the general buckling constraint are included in the design process. The local constraints are treated by means of an interior penalty function and the general buckling load is treated by means of an exterior penalty function. This allows the general buckling constraint to be included in the design process only when it is violated. The self-adjoint nature of the prebuckling and buckling formulations is used to reduce the computational effort. Results for four conical shells and one spherical shell are given.

[Manual-medical differential diagnosis of low back pain including osteopathic procedures].

PubMed

Buchmann, J; Arens, U; Harke, G; Smolenski, U C; Kayser, R

2012-06-01

The differential diagnostic evaluation of painful functional disorders of the lumbosacral and lumbopelvic region, i. e. the so-called “low back pain” is very extensive, but is often reduced to the question of chronicity. The manual medical diagnosis can make a valuable contribution in such cases for determination of structural and functional pathology. Early application of manual medical therapies seems to be effective for peracute complaints. The mobilization of restrictions of the pelvic visceral attachments should be included. In the following review manual medical syndromes are presented that summarize the findings from the musculoskeletal and visceral system. This is intended to facilitate the primary differential diagnostic evaluation, as well as treatment planning. The combination with osteopathic methods is very profitable. A necessary specialist differential diagnosis remains essential.

Combined VEGFR and CTLA-4 blockade increases the antigen-presenting function of intratumoral DCs and reduces the suppressive capacity of intratumoral MDSCs

PubMed Central

Du Four, Stephanie; Maenhout, Sarah K; Niclou, Simone P; Thielemans, Kris; Neyns, Bart; Aerts, Joeri L

2016-01-01

Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models. The combination of axitinib with αCTLA-4 reduced tumor growth and increased survival in both intracranial and subcutaneous models. Investigation of the splenic immune cells showed an increased number of CD4+ and CD8+ T cells after combination treatment. Moreover, combination treatment increased the number of intratumoral dendritic cells (DCs) and monocytic myeloid-derived suppressor cells (moMDSCs). When these immune cell populations were sorted from the subcutaneous and intracranial tumors of mice treated with axitinib+αCTLA-4, we observed an increased antigen-presenting function of DCs and a reduced suppressive capacity of moMDSCs on a per cell basis. Our results suggest that the combination of antiangiogenesis and checkpoint inhibition can lead to an enhanced antitumor effect leading to increased survival. We found that this effect is in part due to an enhanced antitumor immune response generated by an increased antigen-presenting function of intratumoral DCs in combination with a reduced suppressive capacity of intratumoral moMDSCs. PMID:27904768

MiR-24 alleviates cardiomyocyte apoptosis after myocardial infarction via targeting BIM.

PubMed

Pan, L-J; Wang, X; Ling, Y; Gong, H

2017-07-01

Ischemia hypoxia induces cardiomyocyte (CM) apoptosis in the process of acute myocardial infarction (AMI). It was showed that pro-apoptosis factor BIM participates in regulating tumor cell apoptosis under ischemia or hypoxia condition, while its role in CM apoptosis after AMI is still unclear. It was revealed that miR-24 expression was significantly reduced in myocardial tissue after AMI. Bioinformatics analysis exhibits that miR-24 is targeted to the 3'-UTR of BIM. This study aims to investigate the role of miR-24 in mediating BIM expression and CM apoptosis. Dual-luciferase assay was used to confirm the targeted regulation between miR-24 and BIM. Cells were cultured under ischemia hypoxia for 12 h after transfection for 48 h. Cell apoptosis was tested by using flow cytometry. The caspase activity was detected by using spectrophotometry. Wistar rats were divided into four groups, including Sham, AMI, AMI + agomir-control, and AMI + agomir-24 groups. Cardiac function was evaluated by using echocardiography. CM apoptosis was determined by using TUNEL. Infarction area was measured by using evans blue staining. MiR-24 targeted suppressed BIM expression. MiR-24 mimic and/or si-BIM transfection significantly declined the BIM expression, inhibited caspase-9 and caspase-3 activities, and reduced cell apoptosis in H9C2 cells. MiR-24 expression was decreased, while BIM levels were up-regulated in myocardium after AMI. Agomir-24 injection down-regulated the BIM expression in myocardium, reduced CM apoptosis, narrowed infarction area, and improved cardiac function in rats. MiR-24 was reduced, whereas BIM was enhanced in the CM after AMI. MiR-24 up-regulation plays a critical role in decreasing BIM expression, reducing CM apoptosis, and improving cardiac function after AMI.

Development of a comprehensive survey of sexuality issues including a self-report version of the International Spinal Cord Injury sexual function basic data sets.

PubMed

New, P W; Currie, K E

2016-08-01

Questionnaire development, validation and completion. Develop comprehensive survey of sexuality issues including validated self-report versions of the International Spinal Cord Injury male sexual function and female sexual and reproductive function basic data sets (SR-iSCI-sexual function). People with spinal cord damage (SCD) living in the community, Australia from August 2013 to June 2014. An iterative process involving rehabilitation medicine clinicians, a nurse specialising in sexuality issues in SCD and people with SCD who developed a comprehensive survey that included the SR-iSCI-sexual function. Participants recruitment through spinal rehabilitation review clinic and community organisations that support people with SCD. Surveys completed by 154 people. Most were male (n=101, 65.6%). Respondents' median age was 50 years (interquartile range (IQR) 38-58), and they were a median of 10 years (IQR 4-20) after the onset of SCD. Sexual problems unrelated to SCD were reported by 12 (8%) respondents, and 114 (n=75.5%) reported sexual problems because of SCD. Orgasms were much less likely (χ(2)=13.1, P=0.006) to be normal in males (n=5, 5%) compared with females (n=11, 22%). Males had significantly worse (χ(2)=26.0, P=0.001) psychogenic genital functioning (normal n=9, 9%) than females (normal n=13, 26%) and worse (χ(2)=10.8, P=0.013) reflex genital functioning. Normal ejaculation was reported in only three (3%) men. Most (n=26, 52%) women reported reduced or absent menstruation pattern since SCD. The SR-iSCI-sexual function provides a useful tool for researchers and clinicians to collect information regarding patient-reported sexual functioning after SCD and to facilitate comparative studies.

Free Energy and Equilibrium: The Basis of Change in G Degrees = -RT In K for Reactions in Solution.

ERIC Educational Resources Information Center

Barrow, Gordon M.

1983-01-01

Discusses the derivation of a thermodynamic relation. The relation is derived, for reactants in solution, from a treatment of the free energy of the reducing system as a function of the degree of advancement of the solution. Includes microcomputer figures/diagrams produced by programs developed to simulate this study. (JN)

Myth-Busting Is a Bust for Patient Education: Making Salient Older Adults' Misconceptions about Osteoarthritis Fails to Lead to Lasting Corrections

ERIC Educational Resources Information Center

Ansburg, Pamela I.

2016-01-01

Older adults hold many misconceptions about health and wellness that reduce their health literacy. To counter these misconceptions, health educators commonly turn to educational interventions that include myth-busting--making explicit health-related myths and refuting those myths. Because of typical age-related changes in memory functioning, there…

Randomized Trial of Social Rehabilitation and Integrated Health Care for Older People with Severe Mental Illness

ERIC Educational Resources Information Center

Mueser, Kim T.; Pratt, Sarah I.; Bartels, Stephen J.; Swain, Karin; Forester, Brent; Cather, Corinne; Feldman, James

2010-01-01

Objective: The Helping Older People Experience Success (HOPES) program was developed to improve psychosocial functioning and reduce long-term medical burden in older people with severe mental illness (SMI) living in the community. HOPES includes 1 year of intensive skills training and health management, followed by a 1-year maintenance phase.…

OSO-8 soft X-ray experiment (Wisconsin)

NASA Technical Reports Server (NTRS)

1975-01-01

Information for operating and reducing data from the experiment which was designed to map low energy X-ray background emissions from 130 eV to 35 keV is presented. The detectors, counters, data system, and the gas system are discussed along with the functional operation of the subsystems. A command list indicating preconditions and resulting telemetry response for each command is included.

Digital controller design: Continuous and discrete describing function analysis of the IPS system

NASA Technical Reports Server (NTRS)

1977-01-01

The dynamic equations and the mathematical model of the continuous-data IPS control system are developed. The IPS model considered included one flexible body mode and was hardmounted to the Orbiter/Pallet. The model contains equations describing a torque feed-forward loop (using accelerometers as inputs) which will aid in reducing the pointing errors caused by Orbiter disturbances.

Alcohol and Airways Function in Health and Disease

PubMed Central

Sisson, Joseph H.

2007-01-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The impact of alcohol on lung airway functions is dependent on the concentration, duration and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation and probably attenuates the airway inflammation and injury observed in asthma and COPD. Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management and likely worsens outcomes including lung function and mortality in COPD patients. Non-alcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase type 2 (ALDH2). The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation and the interaction with other airway exposure agents, such as cigarette smoke, represent opportunities for future investigation. PMID:17764883

Alcohol and airways function in health and disease.

PubMed

Sisson, Joseph H

2007-08-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The effect of alcohol on lung airway functions is dependent on the concentration, duration, and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation, and probably attenuates the airway inflammation and injury observed in asthma and chronic obstructive pulmonary disease (COPD). Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management, and likely worsens outcomes including lung function and mortality in COPD patients. Nonalcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol- and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase 2. The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation, and the interaction with other airway exposure agents, such as cigarette smoke, represents opportunities for future investigation.

Applications of fibrous substrates containing insolubilized phase change polymers

NASA Technical Reports Server (NTRS)

Vigo, Tyrone L.; Bruno, Joseph S.

1993-01-01

Incorporation of polyethylene glycols into fibrous substrates produces several improved functional properties when they are insolubilized by crosslinking with a methylolamide resin or by polyacetal formation by their reaction with glyoxal. The range of molecular weights of polyols that may be insolubilized is broad as are the curing conditions (0.25-10 min at 80-200C). Most representative fiber types and blends (natural and synthetic) and all types of fabric constructions (woven, nonwoven and knit) have been modified by incorporation of the bound polyols. The most novel property is the thermal adaptability of the modified substrates to many climatic conditions. This adaptability is due to the high latent heat of the crosslinked polyols that function as phase change materials, the hydrophilic nature of the crosslinked polymer and its enhanced thermal conductivity. Other enhanced properties imparted to fabrics include flex and flat abrasion, antimicrobial activity, reduced static charge, resistance to oily soils, resiliency, wind resistance and reduced lint loss. Applications commercialized in the U.S. and Japan include sportswear and skiwear. Several examples of electric sets of properties useful for specific end uses are given. In addition, other uses are biomedical horticultural, aerospace, indoor insulation, automotive interiors and components and packaging material.

Targeted delivery of growth factors in ischemic stroke animal models.

PubMed

Rhim, Taiyoun; Lee, Minhyung

2016-01-01

Ischemic stroke is caused by reduced blood supply and leads to loss of brain function. The reduced oxygen and nutrient supply stimulates various physiological responses, including induction of growth factors. Growth factors prevent neuronal cell death, promote neovascularization, and induce cell growth. However, the concentration of growth factors is not sufficient to recover brain function after the ischemic damage, suggesting that delivery of growth factors into the ischemic brain may be a useful treatment for ischemic stroke. In this review, various approaches for the delivery of growth factors to ischemic brain tissue are discussed, including local and targeting delivery systems. To develop growth factor therapy for ischemic stroke, important considerations should be taken into account. First, growth factors may have possible side effects. Thus, concentration of growth factors should be restricted to the ischemic tissues by local administration or targeted delivery. Second, the duration of growth factor therapy should be optimized. Growth factor proteins may be degraded too fast to have a high enough therapeutic effect. Therefore, delivery systems for controlled release or gene delivery may be useful. Third, the delivery systems to the brain should be optimized according to the delivery route.

Applications of fibrous substrates containing insolubilized phase change polymers

NASA Astrophysics Data System (ADS)

Vigo, Tyrone L.; Bruno, Joseph S.

1993-02-01

Incorporation of polyethylene glycols into fibrous substrates produces several improved functional properties when they are insolubilized by crosslinking with a methylolamide resin or by polyacetal formation by their reaction with glyoxal. The range of molecular weights of polyols that may be insolubilized is broad as are the curing conditions (0.25-10 min at 80-200C). Most representative fiber types and blends (natural and synthetic) and all types of fabric constructions (woven, nonwoven and knit) have been modified by incorporation of the bound polyols. The most novel property is the thermal adaptability of the modified substrates to many climatic conditions. This adaptability is due to the high latent heat of the crosslinked polyols that function as phase change materials, the hydrophilic nature of the crosslinked polymer and its enhanced thermal conductivity. Other enhanced properties imparted to fabrics include flex and flat abrasion, antimicrobial activity, reduced static charge, resistance to oily soils, resiliency, wind resistance and reduced lint loss. Applications commercialized in the U.S. and Japan include sportswear and skiwear. Several examples of electric sets of properties useful for specific end uses are given. In addition, other uses are biomedical horticultural, aerospace, indoor insulation, automotive interiors and components and packaging material.

Influence of field penetration ratios and filamentation on end-effect related hysteretic loss reductions for superconducting strips

NASA Astrophysics Data System (ADS)

Dong, K.; Sumption, M.; Collings, E. W.; Majoros, M.; Yu, H.; Hu, M.

2017-12-01

There are a few key conductor-specific factors which influence the power loss of superconductors; these include critical current, geometry, and normal metal resistivity. This paper focuses on the influence of sample geometry on the power loss of superconducting strips and the effect of filamentation and sample length as a function of the field penetration state of the superconductor. We start with the analytical equations for infinite slabs and strips and then consider the influence of end effects for both unstriated and striated conductor. The loss is then calculated and compared as a function of applied field for striated and unstriated conductors. These results are much more general than they might seem at first glance, since they will be important building blocks for analytic loss calculations for twisted geometries for coated conductors, including helical (Conductor on Round Core, CORC), and twisted (e.g., twist stack cables) geometries. We show that for relatively low field penetration, end effects and reduced field penetration both reduce loss. In addition, for filamentary samples the relevant ratio of length scales becomes the filament width to sample length, thus modifying the loss ratios.

Biological origins of sexual orientation and gender identity: Impact on health.

PubMed

O'Hanlan, Katherine A; Gordon, Jennifer C; Sullivan, Mackenzie W

2018-04-01

Gynecologic Oncologists are sometimes consulted to care for patients who present with diverse gender identities or sexual orientations. Clinicians can create more helpful relationships with their patients if they understand the etiologies of these diverse expressions of sexual humanity. Multidisciplinary evidence reveals that a sexually dimorphic spectrum of somatic and neurologic anatomy, traits and abilities, including sexual orientation and gender identity, are conferred together during the first half of pregnancy due to genetics, epigenetics and the diversity of timing and function of sex chromosomes, sex-determining protein secretion, gonadal hormone secretion, receptor levels, adrenal function, maternally ingested dietary hormones, fetal health, and many other factors. Multiple layers of evidence confirm that sexual orientation and gender identity are as biological, innate and immutable as the other traits conferred during that critical time in gestation. Negative social responses to diverse orientations or gender identities have caused marginalization of these individuals with resultant alienation from medical care, reduced self-care and reduced access to medical care. The increased risks for many diseases, including gynecologic cancers are reviewed. Gynecologic Oncologists can potentially create more effective healthcare relationships with their patients if they have this information. Copyright © 2017 Elsevier Inc. All rights reserved.

Advanced single permanent magnet axipolar ironless stator ac motor for electric passenger vehicles

NASA Technical Reports Server (NTRS)

Beauchamp, E. D.; Hadfield, J. R.; Wuertz, K. L.

1983-01-01

A program was conducted to design and develop an advanced-concept motor specifically created for propulsion of electric vehicles with increased range, reduced energy consumption, and reduced life-cycle costs in comparison with conventional systems. The motor developed is a brushless, dc, rare-earth cobalt, permanent magnet, axial air gap inductor machine that uses an ironless stator. Air cooling is inherent provided by the centrifugal-fan action of the rotor poles. An extensive design phase was conducted, which included analysis of the system performance versus the SAE J227a(D) driving cycle. A proof-of-principle model was developed and tested, and a functional model was developed and tested. Full generator-level testing was conducted on the functional model, recording electromagnetic, thermal, aerodynamic, and acoustic noise data. The machine demonstrated 20.3 kW output at 1466 rad/s and 160 dc. The novel ironless stator demonstated the capability to continuously operate at peak current. The projected system performance based on the use of a transistor inverter is 23.6 kW output power at 1466 rad/s and 83.3 percent efficiency. Design areas of concern regarding electric vehicle applications include the inherently high windage loss and rotor inertia.

In-Vitro Induced Immunosuppression in a Rotary Cell Culture System

NASA Technical Reports Server (NTRS)

Grimm, Elizabeth A.

1998-01-01

The function of the innate immune system is to provide a first-line of defense against infectious organisms, via control of bacterial and viral growth using antigen nonspecific means. These nonspecific immune effectors include macrophages and Natural Killing (NK) cells, and certain cytokines elicited in response to "super antigens" on the infectious agents. This innate system usually keeps most infectious agents from rapidly growing while the adaptive immune system is generating a specific response complete with immunologic memory. Compelling evidence suggests that space flight results in various immunosuppressive effects, including reduced innate and adaptive immune responses. We were particularly concerned with reduced NK activity at landing, and have asked whether the microgravity component of space flight could be responsible for the previously observed NK defect. We have conclusively demonstrated that simulated microgravity as provided by the Synthecon bioreactors does not inhibit the NK function nor the IL-2 activation of lymphokine-activated killing (LAK). Interleukin-2 is the key cytokine responsible for activation of NK cells to express LAK, as well as to support differentiation of lymphocytes during adaptive immune responses. Therefore, we have disproved our original hypothesis based on poor NK in many of the astronauts upon landing.

Mediterranean diet as the diet of choice for patients with chronic kidney disease.

PubMed

Chauveau, Philippe; Aparicio, Michel; Bellizzi, Vincenzo; Campbell, Katrina; Hong, Xu; Johansson, Lina; Kolko, Anne; Molina, Pablo; Sezer, Siren; Wanner, Christoph; Ter Wee, Pieter M; Teta, Daniel; Fouque, Denis; Carrero, Juan J

2018-05-01

Traditional dietary management of chronic kidney disease (CKD) focuses on the quantity within the diet of energy and protein, and the restriction of single micronutrients, with little mention of dietary quality. Dietary patterns that are more plant-based, lower in meat (including processed meat), sodium and refined sugar, and have a higher content of grains and fibres are now included in multiple clinical guidelines for chronic disease prevention. The Mediterranean diet (MD) has been associated with reduced cardiovascular disease incidence in both observational and interventional studies. A wealth of evidence links MD with other beneficial effects on chronic diseases such as diabetes, obesity or cognitive health. This review examines each constituent of the classical MD and evaluates their suitability for the management of patients with CKD. We also evaluate the potential hyperkalaemia risk of increasing fruit and vegetable intake. Overall, a decrease in net endogenous acid production and increase in fibre may lead to a better control of metabolic acidosis. This, together with other putative favourable effects of MD on endothelial function, inflammation, lipid profile and blood pressure, provide mechanistic pathways to explain the observed reduced renal function decline and improved survival in CKD patients adhering to an MD.

Assessing Stress-Related Treatment Needs among Girls at Risk for Poor Functional Outcomes: The Impact of Cumulative Adversity, Criterion Traumas, and Non-Criterion Events

PubMed Central

Lansing, Amy E.; Plante, Wendy Y.; Beck, Audrey N.

2016-01-01

Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: 1) an average of 14 adverse Criterion-A and non-Criterion event exposures; 2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; 3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and 4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. PMID:27745922

Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

PubMed

Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

2017-05-01

Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

High density diffusion-free nanowell arrays.

PubMed

Takulapalli, Bharath R; Qiu, Ji; Magee, D Mitchell; Kahn, Peter; Brunner, Al; Barker, Kristi; Means, Steven; Miersch, Shane; Bian, Xiaofang; Mendoza, Alex; Festa, Fernanda; Syal, Karan; Park, Jin G; LaBaer, Joshua; Wiktor, Peter

2012-08-03

Proteomics aspires to elucidate the functions of all proteins. Protein microarrays provide an important step by enabling high-throughput studies of displayed proteins. However, many functional assays of proteins include untethered intermediates or products, which could frustrate the use of planar arrays at very high densities because of diffusion to neighboring features. The nucleic acid programmable protein array (NAPPA) is a robust in situ synthesis method for producing functional proteins just-in-time, which includes steps with diffusible intermediates. We determined that diffusion of expressed proteins led to cross-binding at neighboring spots at very high densities with reduced interspot spacing. To address this limitation, we have developed an innovative platform using photolithographically etched discrete silicon nanowells and used NAPPA as a test case. This arrested protein diffusion and cross-binding. We present confined high density protein expression and display, as well as functional protein-protein interactions, in 8000 nanowell arrays. This is the highest density of individual proteins in nanovessels demonstrated on a single slide. We further present proof of principle results on ultrahigh density protein arrays capable of up to 24000 nanowells on a single slide.

Exercise counteracts declining hippocampal function in aging and Alzheimer's disease.

PubMed

Intlekofer, Karlie A; Cotman, Carl W

2013-09-01

Alzheimer's disease (AD) afflicts more than 5.4 million Americans and ranks as the most common type of dementia (Thies and Bleiler, 2011), yet effective pharmacological treatments have not been identified. Substantial evidence indicates that physical activity enhances learning and memory for people of all ages, including individuals that suffer from cognitive impairment. The mechanisms that underlie these benefits have been explored using animal models, including transgenic models of AD. Accumulating research shows that physical activity reinstates hippocampal function by enhancing the expression of brain-derived neurotrophic factor (BDNF) and other growth factors that promote neurogenesis, angiogenesis, and synaptic plasticity. In addition, several studies have found that physical activity counteracts age- and AD-associated declines in mitochondrial and immune system function. A growing body of evidence also suggests that exercise interventions hold the potential to reduce the pathological features associated with AD. Taken together, animal and human studies indicate that exercise provides a powerful stimulus that can countervail the molecular changes that underlie the progressive loss of hippocampal function in advanced age and AD. 2012 Published by Elsevier Inc

Generation of mice lacking DUF1220 protein domains: effects on fecundity and hyperactivity.

PubMed

Keeney, J G; O'Bleness, M S; Anderson, N; Davis, J M; Arevalo, N; Busquet, N; Chick, W; Rozman, J; Hölter, S M; Garrett, L; Horsch, M; Beckers, J; Wurst, W; Klingenspor, M; Restrepo, D; de Angelis, M Hrabě; Sikela, J M

2015-02-01

Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question, we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. In a hypothesis generating exercise, these mice were evaluated by 197 different phenotype measurements. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ(2) = 19.1, df = 2, p = 7.0 × 10(-5)). Further extensive phenotypic analyses suggest hyperactivity (p < 0.05) of DUF1220 mice and changes in gene expression levels of brain associated with distinct neurological functions and disease. Other changes that met statistical significance include an increase in plasma glucose concentration (as measured by area under the curve, AUC 0-30 and AUC 30-120) in male mutants, fasting glucose levels, reduce sodium levels in male mutants, increased levels of the liver functional indicator ALAT/GPT in males, levels of alkaline phosphatase (also an indicator of liver function), mean R and SR amplitude by electrocardiography, elevated IgG3 levels, a reduced ratio of CD4:CD8 cells, and a reduced frequency of T cells; though it should be noted that many of these differences are quite small and require further examination. The linking of DUF1220 loss to a hyperactive phenotype is consistent with separate findings in which DUF1220 over expression results in a down-regulation of mitochondrial function, and potentially suggests a role in developmental metabolism. Finally, the substantially reduced fecundity we observe associated with KO mice argues that the ancestral DUF1220 domain provides an important biological functionthat is critical to survivability and reproductive success.

FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis.

PubMed

Tan, BeeShin; Anaka, Matthew; Deb, Siddhartha; Freyer, Claudia; Ebert, Lisa M; Chueh, Anderly C; Al-Obaidi, Sheren; Behren, Andreas; Jayachandran, Aparna; Cebon, Jonathan; Chen, Weisan; Mariadason, John M

2014-01-15

The Forkhead box P3 (FOXP3) transcription factor is the key driver of regulatory T cell (Treg cells) differentiation and immunosuppressive function. In addition, FOXP3 has been reported to be expressed in many tumors, including melanoma. However, its role in tumorigenesis is conflicting, with both tumor suppressive and tumor promoting functions described. The aim of the current study was to characterize the expression and function of FOXP3 in melanoma. FOXP3 expression was detected by immunohistochemistry (IHC) in 12% (18/146) of stage III and IV melanomas. However expression was confined to fewer than 1% of cells in these tumors. Stable over-expression of FOXP3 in the SK-MEL-28 melanoma cell line reduced cell proliferation and clonogenicity in vitro, and reduced xenograft growth in vivo. FOXP3 over-expression also increased pigmentation and the rate of apoptosis of SK-MEL-28 cells. Based on its infrequent expression in human melanoma, and its growth inhibitory and pro-apoptotic effect in over-expressing melanoma cells, we conclude that FOXP3 is not likely to be a key tumor suppressor or promoter in melanoma.

Narrative discourse deficits in amyotrophic lateral sclerosis.

PubMed

Ash, Sharon; Menaged, Anna; Olm, Christopher; McMillan, Corey T; Boller, Ashley; Irwin, David J; McCluskey, Leo; Elman, Lauren; Grossman, Murray

2014-08-05

We examined narrative discourse in amyotrophic lateral sclerosis (ALS) to assess the role of executive functioning in support of language and the neuroanatomical basis for such support. We analyzed a semistructured speech sample in 26 patients with ALS and 19 healthy seniors for narrative discourse features of coherence. Regression analyses related a measure of discourse coherence ("local connectedness") to gray matter atrophy and reduced white matter fractional anisotropy. Patients with ALS were impaired relative to controls on measures of discourse adequacy, including local connectedness and maintenance of the theme. These discourse measures were related to measures of executive functioning but not to motor functioning. Regressions related local connectedness to gray matter atrophy in ventral and dorsal prefrontal regions and to reduced fractional anisotropy in white matter tracts mediating projections between prefrontal regions. Patients with ALS exhibit deficits in their ability to organize narrative discourse. These deficits appear to be related in part to executive limitations. Consistent with the hypothesis that ALS is a multisystem disorder, this deficit is related to disease in prefrontal regions. © 2014 American Academy of Neurology.